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Jonas DE, Crotty K, Yun JDY, et al. Screening for Prediabetes and Type 2 Diabetes Mellitus: An Evidence Review for the U.S. Preventive Services Task Force [Internet]. Rockville (MD): Agency for Healthcare Research and Quality (US); 2021 Aug. (Evidence Synthesis, No. 207.)
Screening for Prediabetes and Type 2 Diabetes Mellitus: An Evidence Review for the U.S. Preventive Services Task Force [Internet].
Show detailsAdditional Detailed Results for Interventions for Screen-Detected Type 2 Diabetes (KQ 4)
The China Da Qing Diabetes Prevention Outcomes Study (CDQDPOS) evaluated a lifestyle intervention with 30 years of followup in China, among people with prediabetes without requiring additional risk factors for diabetes or mortality.225–228 Here we present additional outcomes from that study not included in the main report. The Da Qing results indicate that an absolute decrease in diabetes incidence of about 24 percent over 6 years (43.6% vs. 67.7%) for participants participating in a lifestyle intervention vs. control225–227 resulted in a 7 percent reduction in stroke at 30 years (39% vs. 46%; HR, 0.70 [95% CI, 0.59 to 0.96]) and a nonsignificant trend toward reduced coronary heart disease (15% vs. 19%; HR, 0.73 [95% CI, 0.51 to 1.04]) and heart failure (10% vs. 12%; HR, 0.71 [95% CI, 0.48 to 1.04]).228 At 30 years, there was also a reduction in a composite of microvascular outcomes (19% vs. 24%; HR, 0.65 [95% CI, 0.45 to 0.95]) and retinopathy (14% vs. 19%; HR, 0.60 [95% CI, 0.38 to 0.95]).228 There was no significant difference between intervention and control groups in nephropathy (4% vs. 5%; HR, 0.68 [95% CI, 0.36 to 1.28]) or neuropathy (3% vs. 5%; HR, 0.57 [95% CI, 0.24 to 1.36]) at the 30-year follow up.228 The HRs presented here are adjusted for age only.
One study reported on QoL outcomes specific to the ADDITION-Netherlands cohort at 1-117 and 3-year followups (see Appendix E Table 1).95 Another study reported 5-year QoL outcomes for all three ADDITION-Europe countries (the United Kingdom [2 sites], Denmark and the Netherlands) and conducted a pooled-estimate across the four study sites (see Appendix E Table 2).243 QoL outcomes evaluated included self-reported health status assessed using the 36-item Short Form Health Survey (SF-36), which includes both a physical and mental component score, and the EuroQol 5 dimensions (EQ-5D) questionnaire, which covers five dimensions of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and includes a Visual Analog Scale (EQ-VAS). General well-being was assessed with the Well-Being Questionnaire (W-BQ12), which measures multiple aspects of well-being, and the Audit of Diabetes-Dependent QoL (ADDQoL) questionnaire was used to assess the impact of diabetes on QoL. Of the 2861 participants alive at followup, 2217 participants completed QoL questionnaires.
At the 5-year followup, pooled analysis across four sites (U.K. Cambridge, U.K. Leicester, Denmark, and the Netherlands) found no statistically significant difference in any QoL measure among patients with screen-detected type 2 diabetes receiving intensive multifactorial treatment and those receiving routine care (Appendix E Table 2).243 This finding of no difference between groups was mirrored in the individual results from each of the four sites with the exception of the U.K. Leicester site, which reported significant differences favoring the intensive treatment group for the SF-36 physical component score (mean difference between groups, −3.78 [95% CI, −7.30 to −0.26]), the EQ-VAS (mean difference between groups, −8.37 [95% CI, −15.15 to −1.59]), and the ADDQoL (mean difference between groups, −1.23 [95% CL, −2.25 to −0.21]) (Appendix E Table 2).243 Similarly, among patients in the ADDITION-Netherlands study, SF-36 QoL measures assessed at the 1- and 3-year followups, and EQ5D QoL measures assessed at the 3-year followup were not significantly different between those receiving intensive multifactorial treatment and those receiving routine care (Appendix E Table 1).95,117
None of the included publications reported on symptomatic chronic kidney disease, end-stage renal disease, requirement for dialysis, or need for transplantation. The addition-Europe study reported on nephropathy, defined as the presence of either microalbuminuria or macroalbuminuria, at 5 years.76 Microalbuminuria (defined as urinary-albumin-creatinine ratio [ACR] ≥ 2.5 mg/mmol for men and ≥ 3.5 mg/mmol for women), macroalbuminuria (defined as ACR ≥25 mg/mmol) and estimated glomerular filtration rate (eGFR) were used to assess for nephropathy. Of 2861 people still alive at 5 years, 87.1% (n=2493) had data for urinary ACR, and 94.7 percent (n=2710) had data for eGFR (Appendix E Table 3). Pooled analysis from across the four ADDITION-Europe sites (U.K. Cambridge, U.K. Leicester, Denmark, and the Netherlands) found that at 5-years followup, there was no difference in the presence of any albuminuria among patients with screen-detected type 2 diabetes receiving intensive multifactorial treatment and those receiving routine care (22.7% vs. 24.4%, respectively, OR, 0.88 [95% CI, 0.72 to 1.07].76 The pooled estimate for the presence of macroalbuminuria also found no difference between groups (4.0% vs. 3.4%, OR, 1.15 [95% CI, 0.76 to 1.74]), and there was no difference in mean eGFR (4.31 ml/minute versus 6.44 ml/min, mean difference, −1.39 ml/minute [95% CI, −2.97 to 0.19) (Appendix E Table 3).76 Prespecified subgroup analysis found no significant interactions based on sex or age.
None of the included publications reported on vision changes, symptoms of retinopathy, or blindness. The addition-Europe study reported on any retinopathy as a secondary outcome at 5-years followup.76 Retinopathy was assessed using gradable digital images that were categorized as “any retinopathy compared with no retinopathy” and “severe or proliferative retinopathy compared with no, mild or moderate retinopathy using the Early Treatment Diabetic Retinopathy Study (ETDRS) semiquantitative scale. Of 2861 people still alive at 5 years, retinal photographs were retrieved for 76.5 percent (n=2190) (Appendix E Table 3). Pooled analysis from across the four ADDITION-Europe sites (U.K. Cambridge, U.K. Leicester, Denmark, and the Netherlands) found that at 5-years followup, there was no statistically significant difference in the presence of any retinopathy among patients with screen-detected type 2 diabetes receiving intensive multifactorial treatment and those receiving routine care (10.1% vs. 12.1%, respectively, OR, 0.84 [95% CI, 0.64 to 1.10] (Appendix E Table 3).76 Prespecified subgroup analysis found no significant interactions based on sex or age.
The ADDITION-Europe study reported on any neuropathy as a secondary outcome at 5-years followup,76 and ADDITION-Denmark reported on a variety of peripheral neuropathy measures at 6-years followup.245 Peripheral neuropathy was assessed using the self-administered Michigan Neuropathy Screening Instrument (MNSI) (which defined patients as having peripheral neuropathy if they had a score of ≥7); the Brief Pain Inventory Short form (which defined patients as having painful diabetic neuropathy if they indicated having pain in both legs and /or both arms); light touch sensory testing (which defined peripheral neuropathy as the inability to feel one or more test sites); and the Vibration Detection Threshold (VDT) (which defined peripheral neuropathy as values ≥95th percentile)76,245 Of 2861 people in the ADDITION-Europe study still alive at 5 years, peripheral neuropathy data were available for 80.8 percent (n=2312). Of 1533 people enrolled in the ADDITION-Denmark study, 6-year peripheral neuropathy data were available on 1161 (Appendix E Table 3).245
Pooled analysis from across the four ADDITION-Europe sites (U.K. Cambridge, U.K. Leicester, Denmark, and the Netherlands) (n=2312) found that at 5-years followup, there was no statistically significant difference in the presence of any neuropathy among patients with screen-detected type 2 diabetes receiving intensive multifactorial treatment and those receiving routine care (4.86% vs. 5.91%, respectively, OR, 0.95 [95% CI, 0.68 to 1.34] (Appendix E Table 3).76 Similarly, across multiple measures at 6-years followup in the ADDITION-Denmark study, there was no significant difference in the prevalence of peripheral neuropathy among those receiving intensive multifactorial treatment and those receiving routine care (data shown in figure only).245
Additional Detailed Results for KQ 8
The Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial recruited people with prediabetes across several countries, with a median of 3 years followup.253–255 The DREAM results found an absolute decrease in diabetes incidence of about 14 percent over 3 years (10.6% vs. 25.0% after rosiglitazone vs. control)254 and no significant difference in all-cause mortality (1.1% vs. 1.3%) or cardiovascular events (composite of cardiovascular death, cardiac resuscitation, MI, stroke, revascularization procedure, new angina with documented ischemia or heart failure) over the same time period (2.9% vs. 2.1%).255
The STOP NIDDM trial recruited people with prediabetes and BMI between 25 and 40 across several countries, who were randomized to acarbose or placebo with mean 3.3 years of followup for diabetes and cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, or peripheral vascular disease).235,236 The STOP NIDDM results found that an absolute decrease in diabetes incidence of about 9 percent over 3.3 years with acarbose (32.4% vs. 41.5% for acarbose vs. control)235 and 2.5 percent fewer major cardiovascular events (2.2% vs. 4.7%).236
The SCALE trial recruited people across 27 countries with prediabetes and BMI>30, or prediabetes and BMI>27 with hypertension and/or dyslipidaemia.115 Participants were randomized to liraglutide or placebo with 3.3 years of followup to diabetes and a composite of cardiovascular events (acute coronary syndrome, cerebrovascular, heart failure, stent thrombosis, revascularization procedure, hospitalizations for cardiac arrhythmia). The SCALE reported an absolute decrease in diabetes incidence of about 4 percent over 3 years (1.7% vs. 6.1% of participants after a liraglutide vs. control) and did not find a statistically significant reduction in cardiovascular events over the same time period.115
The Actos Now For Prevention of Diabetes Trial (ACT NOW) trial recruited people with IGT and BMI>25 (>22 in Asian Americans) and at least one other risk factor for diabetes in the United States.251,252 Participants were randomized to Pioglitazone or placebo, with 2.2 years followup to diabetes and a cardiovascular composite (atypical chest pain, cardiac arrhythmia, carotid endarterectomy, coronary artery bypass/revascularization, coronary artery disease without revascularization, new or worsening angina, new or worsening CHF, nonfatal MI, peripheral vascular disease with claudication or revascularization, TIA, malignant hypertension). The ACT NOW results found an absolute decrease in diabetes incidence of about 12 percent over 2 years (5.0% vs. 16.7% of participants after pioglitazone vs. control)251,252 and no difference in cardiovascular events over the same time period.251
The Let’s Prevent Diabetes study recruited people with screen detected prediabetes in the United Kingdom for a lifestyle intervention with 3-year followup to all outcomes.86,118 Incidence of diabetes was similar in the intervention and control groups (14.3% vs. 15.5%) as was quality of life (measured using a 15 dimensional score 0.91 vs. 0.91).86,118
Appendix E Table 1Quality of Life Outcomes at 1- and 3-Year Followups Among Individuals With Screen-Detected Type 2 Diabetes (KQ 4)
|
First Author, Year Trial Name Country | QoL Outcomes at 1-Year Followup | QoL Outcomes at 3-Year Followup |
|---|---|---|
|
van den Donk, 201095 Janssen, 2009117 ADDITION-Netherlands Netherlands |
G1: N=255 G2: N=243 Short form-36 Mean (SD) Physical functioning G1 baseline: 77.4 (21.9) G1 1-year: 80.1 (21.2) G2 baseline: 78.3 (22.0) G2 1-year:78.1 (23.2) p=0.22 Role physical G1 baseline: 82.8 (31.4) G1 1-year: 80.3 (35.0) G2 baseline: 84.9 (30.0) G2 1-year: 81.1 (33.5) p=0.93 Bodily pain G1 baseline: 80.8 (22.1) G1 1-year: 79.2 (22.7) G2 baseline: 84.7 (20.7) G2 1-year: 82.2 (22.4) p=0.97 General health G1 baseline: 59.1 (11.5) G1 1-year: 63.3 (18.4) G2 baseline: 59.7 (12.0) G2 1-year: 64.4 (18.1) p=0.63 Vitality: G1 baseline: 49.3 (14.4) G1 1-year: 64.8 (20.4) G2 baseline: 52.2 (13.2) G2 1-year: 67.1 (18.4) p=0.81 Social functioning G1 baseline: 87.9 (20.0) G1 1-year: 83.0 (22.0) G2 baseline: 89.0 (17.2) G2 1-year: 85.7 (19.2) p=0.37 Role emotional G1 baseline: 88.2 (28.6) G1 1-year: 86.2 (30.9) G2 baseline: 85.4 (32.4) G2 1-year: 89.9 (26.0) p=0.25 |
G1: N=145-163 G1: N=160-178 Short form 36 Mean (SEM) Physical functioning G1 baseline: 77.6 (1.7) G1 3 years: 77.3 (1.8) Change: −0.3 (−3.4, 2.8) G2 baseline: 78.4 (1.8) G2 3 years:79.1 (1.7) Change: 0.7 (−2.5, 3.8) Difference: −1.2 (−6.1, 3.7) Role physical G1 baseline: 83.8 (2.3) G1 3 years: 76.6 (2.7) G1 Change: −7.3 (−12.4, −2.1) G2 baseline: 85.4 (2.4) G2 3 years: 83.4 (2.4) G2 Change: −2.0 (−7.0, 3.0) Difference: −5.3 (−12.5, 1.9) Bodily pain G1 baseline: 80.5 (1.7) G1 3 years: 78.0 (1.8) G1 Change: −2.5 (−5.7, 0.7) G2 baseline: 84.7 (1.7) G2 3 years: 81.1 (1.6) G2 Change: −3.6 (−6.8, −0.4) Difference: 1.1 (−3.4, 5.6) General health G1 baseline: 59.5 (0.9) G1 3 years: 64.2 (1.5) G1 Change: 4.7 (2.3, 7.2) G2 baseline: 59.6 (1.0) G2 3 years: 65.8 (1.5) G2 Change: 6.2 (3.7, 8.7) Difference: −1.5 (−5.0, 2.0) Vitality: G1 baseline: 49.2 (1.1) G1 3 years: 65.6 (1.6) G1 Change: 16.4 (13.0, 19.7) G2 baseline: 51.4 (1.1) G2 3 years: 67.7 (1.6) G2 Change: 16.3 (13.4, 19.2) Difference: 0.03 (−4.6, 4.7) Social functioning G1 baseline: 89.3 (1.4) G1 3 years: 83.2 (1.7) G1 Change: −6.1 (−9.4, −2.8) G2 baseline: 90.0 (1.3) G2 3 years: 86.2 (1.6) G2 Change: −3.8 (−6.8, −0.9) Difference: −2.3 (−7.0, 2.3) Role emotional G1 baseline: G1 baseline: 89.3 (2.1) G1 3 years: 84.8 (2.4) G2 Change: −4.6 (−10.3, 1.1) 87.9 (2.4) G2 3 years: 87.0 (2.4) G2 Change: −0.8 (−5.6,3.9) Difference: −3.7 (−11.2,3.7) Mental health G1 baseline: 68.1 (1.0) G1 3 years: 75.9 (1.4) Change: 7.8 (5.1;10.5) G2 baseline: 71.1 (0.9) G2 3 years: 79.7 (1.2) Change: 8.6 (6.1,11.1) Difference: −0.8 (−4.5,2.8) EQ5D G1 baseline: 0.81 (0.02) G1 3 years: 0.81 (0.02) G1 change: 0.0002 (−0.03,0.03) G2 baseline: 0.81 (0.02) G2 3 years: 0.81 (0.02) G2 change: 0.001 (−0.03,0.03) Difference: −0.002 (−0.04,0.04) |
Abbreviations: ADDITION=Anglo-Dutch-Danish Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care; G=Group; SD=standard deviation; SEM=Standard Error of the Mean.
Appendix E Table 2Quality of Life Outcomes at 5-Year Followup Among Individuals With Screen-Detected Type 2 Diabetes (KQ 4)
|
First Author, Year Trial Name Country | Denmark | U.K., Cambridge | U.K. Leicester |
Netherlands 5-Year Followup |
Pooled Across Countries Mean Difference (95% CI) |
|---|---|---|---|---|---|
|
van den Donk, 2013243 Simmons, 201676 ADDITION-Europe Denmark, U.K., Netherlands |
At 5-year followup SF-36 (n=1093) PCS mean score (SD) G1: 46.7 (10.0) G2: 46.7 (9.6) Mean difference (95% CI) −0.32 (−1.36, 0.72) MCS mean score (SD) G1: 55.3 (9.1) G2: 54.9 (8.5) Mean difference (95% CI) −0.63 (−1.70, 0.44) EuroQol EQ-5D (n=1158) mean score (SD) G1: 0.85 (0.21) G2: 0.84 (0.22) Mean difference (95% CI) −0.02 (−0.04, 0.00) EQ-VAS (n=1153) mean score (SD) G1: 76.9 (16.9) G2: 76.4 (18.5) Mean difference (95% CI) −1.05 (−3.00, 0.90) W-BQ12 General (n-1127) mean score (SD) G1: 28.5 (5.9) G2: 28.1 (6.3) Mean difference (95% CI) −0.60 (−1.28, 0.08) Negative (n=1147) mean score (SD) G1: 1.1 (2.0) G2: 1.1 (1.8) Mean difference (95% CI) 0.10 (−0.12, 0.32) Positive (n=1148) mean score (SD) G1: 9.4 (2.5) G2: 9.2 (2.8) Mean difference (95% CI) −0.31 (−0.63, 0.01) Energy (n=1144) mean score (SD) G1: 8.1 (2.7) G2: 8.0 (2.8) Mean difference (95% CI) −0.21 (−0.52, 0.10) ADDQoL (n=900) G1: −0.73 (1.15) G2: −0.69 (1.07) Mean difference (95% CI) 0.02 (−0.13, 0.17) |
At 5-year followup SF-36 (n=660) PCS mean score (SD) G1: 43.9 (11.6) G2: 44.6 (11.3) Mean difference (95% CI) 0.83 (−0.96, 2.61) MCS mean score (SD) G1: 53.4 (9.0) G2: 54.6 (8.4) Mean difference (95% CI) 1.14 (−0.14, 2.41) EuroQol EQ-5D (n=663) mean score (SD) G1: 0.81 (0.23) G2: 0.83 (0.22) Mean difference (95% CI) 0.02 (−0.01, 0.05) EQ-VAS (n=671) mean score (SD) G1: 76.1 (18.0) G2: 78.4 (16.4) Mean difference (95% CI) 2.72 (−0.09, 5.52) W-BQ12 General (n=656) mean score (SD) G1: 25.5 (6.5) G2: 26.4 (5.9) Mean difference (95% CI) 0.81 (−0.10, 1.71) Negative (665) mean score (SD) G1: 1.7 (2.4) G2: 1.4 (2.1) Mean difference (95% CI) −0.28 (−0.61, 0.06) Positive (n=667) mean score (SD) G1: 8.2 (2.8) G2: 8.4 (2.7) Mean difference (95% CI) 0.35 (−0.28, 0.57) Energy (n=667) mean score (SD) G1: 7.0 (2.7) G2: 7.3 (2.6) Mean difference (95% CI) 0.35 (−0.01, 0.72) ADDQoL (n=586) G1: −0.84 (1.29) G2: −0.87 (1.30) Mean difference (95% CI) −0.07 (−0.28, 0.13) |
At 5-year followup SF-36 (n=143) PCS mean score (SD) G1: 44.3 (11.4) G2: 43.4 (10.5) Mean difference (95% CI) −3.78 (−7.30, −0.26) MCS mean score (SD) G1: 50.9 (10.1) G2: 52.2 (9.8) Mean difference (95% CI) −1.51 (−5.33, 2.31) EuroQol EQ-5D (n=145) mean score (SD) G1: 0.75 (0.31) G2: 0.79 (0.23) Mean difference (95% CI) −0.02 (−0.09, 0.06) EQ-VAS (n=148) mean score (SD) G1: 78.3 (16.3) G2: 74.8 (18.4) Mean difference (95% CI) −8.37 (−15.15, −1.59) W-BQ12 General (n=136) mean score (SD) G1: 25.3 (6.7) G2: 25.0 (6.3) Mean difference (95% CI) −2.21 (−4.64, 0.22) Negative (n=145) mean score (SD) G1: 1.9 (2.5) G2: 2.1 (2.5) Mean difference (95% CI) 0.78 (−0.33, 1.89) Positive (n=144) mean score (SD) G1: 8.2 (2.6) G2: 8.0 (2.9) Mean difference (95% CI) −0.99 (−2.06, 0.09) Energy (n=140) mean score (SD) G1: 7.1 (2.7) G2: 7.1 (2.3) Mean difference (95% CI) −0.48 (−1.37, 0.41) ADDQoL (n=126) G1: −1.20 (1.78) G2: −2.39 (2.52) Mean difference (95% CI) −1.23 (−2.25, −0.21) |
At 5-year followup SF-36 (n=321) PCS mean score (SD) G1: 46.8 (10.4) G2: 47.0 (10.5) Mean difference (95% CI) 0.42 (−1.63, 2.46) MCS mean score (SD) G1: 54.3 (8.2) G2: 53.7 (7.4) Mean difference (95% CI) −0.64 (−2.53, 1.26) EuroQol EQ-5D (n=320) mean score (SD) G1: 0.86 (0.18) G2: 0.82 (0.26) Mean difference (95% CI) −0.03 (−0.07, 0.01) EQ-VAS (n=319) mean score (SD) G1: 76.5 (13.7) G2: 75.3 (15.6) Mean difference (95% CI) −1.87 (−4.92, 1.18) W-BQ12 General (n=312) mean score (SD) G1: 27.6 (6.3) G2: 27.4 (5.7) Mean difference (95% CI) −0.45 (−1.82, 1.18) Negative (n=318) mean score (SD) G1: 1.1 (1.9) G2: 1.1 (1.8) Mean difference (95% CI) 0.06 (−0.37, 0.48) Positive (n=321) mean score (SD) G1: 8.0 (3.1) G2: 8.1 (2.6) Mean difference (95% CI) −0.13 (−0.80, 0.54) Energy (n=316) mean score (SD) G1: 8.5 (2.6) G2: 8.5 (2.3) Mean difference (95% CI) −0.08 (−0.61, 0.45) ADDQoL (n=304) G1: −0.55 (0.86) G2: −0.55 (0.92) Mean difference (95% CI) 0.02 (−0.18, 0.22) |
At 5-year followup SF-36 PCS Pooled estimate −0.21 (−1.48, 1.05) I2=44% SF-36 MCS Pooled estimate −0.01 (−1.21, 0.99) I2=50% EQ-5D Pooled estimate −0.01 (−0.03, 0.02) I2=49% EQ-VAS Pooled estimate −1.17 (−4.20, 1.87) I2=73% W-BQ-general Pooled estimate −0.32 (−1.31, 0.66) I2=66% W-BQ-negative Pooled estimate 0.01 (−0.25, 0.27) I2=45% W-BQ-positive Pooled estimate −0.19 (−0.53, 0.15) I2=41% W-BQ-energy Pooled estimate −0.04 (−0.38, 0.31) I2=54% ADDQoL Pooled estimate −0.04 (−0.20, 0.13) I2=50% |
Abbreviations: ADDITION=Anglo-Dutch-Danish Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care; ADDQoL=Anglo-Dutch-Danish Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care quality of life; CI=confidence interval; EQ-5D=EuroQol 5 Dimensions; EQ-VAS=EuroQol Visual Analogue Scale; G=Group; MCS=mental component scale; PCS=physical component scale; SD=standard deviation; SF-36=36-item Short Form Health Survey; U.K.=United Kingdom; W-BQ=12-Item short form of the Well-Being Questionnaire.
Appendix E Table 3Results of Outcomes for Chronic Kidney Disease, Retinopathy, and Neuropathy Among Individuals With Screen-Detected Type 2 Diabetes (KQ 4)
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First Author, Year Trial Name Country |
Chronic Kidney Disease G1 N (%) G2 N (%) HR (95% CI) |
Visual Impairment G1 N (%) G2 N (%) HR (95% CI) |
Neuropathy G1 N (%) G2 N (%) HR (95% CI) |
|---|---|---|---|
|
Simmons, 201676 ADDITION-Europe Denmark, U.K., the Netherlands |
At 5-year followup Any albuminuria (yes/no) # patients (%) G1: 316/1392 (22.7) G2: 269/1101 (24.4) OR, (95% CI) 0.88 (0.72, 1.07) Macroalbuminuria # patients (%) G1: 56/1392 (4.0) G2: 37/1101 (3.4) OR, (95% CI) 1.15 (0.76,1.74) Estimated Glomerular Filtration Rate (eGFR) (n=2710) Mean (SD) G1: 4.31 (0.49) ml/min G2: 6.44 (0.9) ml/min Mean difference (95% CI) −1.39 (−2.97, 0.19) ml/min No interaction based on age or sex |
At 5-year followup Any retinopathy (yes/no) # patients (%) G1: 125/1232 (10.1) G2: 116/958 (12.1) OR, (95% CI) 0.84 (0.64, 1.10) No interaction based on age or sex |
At 5-year followup Any neuropathy (yes/no) G1: 63/1296 (4.86) G2: 60/1016 (5.91) OR, (95% CI) 0.95 (0.68, 1.34) |
|
Charles, 2011245 ADDITION-Denmark Denmark | NR | NR |
At 6-years followup (n=1161) Light touch sensation, 1/8 Prevalence (SD) G1 (n=387): 17.8% (14.1, 22.0) G2 (n=231): 20.3% (15.3, 26.1) Vibration detection threshold, >95th percentile Prevalence (SD) G1 (n=235): 22.6% (17.2, 28.1) G2 (n=136): 25.7% (18.3, 33.2) Light touch + VDT Prevalence (SD) G1 (n=229): 30.1% (24.1, 36.1) G2 (n=135) 34.8% (26.7, 43.0) MNSI Questionnaire, cut ≥7 Prevalence (SD) G1 (n=656): 8.7% (6.5, 10.9) G2 (n=430): 9.3% (6.5, 12.1) Pain Prevalence (SD) G1 (n=581): 4.6% (2.9, 6.4) G2 (n=400): 4.5% (2.5, 6.5) For all outcomes: OR point estimate favored G1 but was nonsignificant (data was presented visually, data NR) |
Abbreviations: ADDITION=Anglo-Dutch-Danish Study of Intensive Treatment in People with Screen Detected Diabetes in Primary Care; CI=confidence interval; eGFR=Estimated Glomerular Filtration Rate; MNSI=Michigan Neuropathy Screening Instrument; NR=not reported; OR=odds ratio; SD=standard deviation; VDT=Vibration Detection Threshold.
Appendix E Table 4Characteristics of Studies that Evaluated Interventions for People With Prediabetes (KQs 4, 6, 7, 9)
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Author, Year Trial Name | Design; Setting | Participants |
Groups (No. Participants) | Followup, y | Age, Mean (SD or IQR), y | No. (%) F | No. (%) Non-white | HbA1C Mean (%)(SD) | FPG, Mean (SD) mg/dL | BMI, Mean, kg/m2 |
Mean BP Systolic (mm Hg) (SD) Mean BP Diastolic (mm Hg) (SD) No. (%) Smokers | Quality |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Studies Evaluating Lifestyle Interventions (including those that also evaluated medications) | ||||||||||||
|
Ackermann, 2015139 Reaching Out to Prevent Increases in Diabetes (RAPID) | RCT; 9 urban primary care clinics in Indianapolis, Indiana | Low-income adults with IFG, IGT, or elevated HbA1c, BMI ≥24 kg/m2, and no diagnosis of DM |
G1: Group-based YMCA DPP (YDPP) intervention (n=257) G2: Usual care plus brief counseling & information on community resources (n=252) | 1 |
G1: 50.8 (12.2) G2: 51.2 (12.0) |
G1: 187 (72.8) G2: 173 (68.7) |
G1: 166 (65) G2: 165 (65) |
G1 6.1 (0.3) G2 6.0 (0.3) | NR |
G1: 37.1 (8.7) G2: 36.5 (8.3) |
Overall: 132.2 (14.6) NR NR G1: 133.5 (15.2) G2: 130.9 (13.8) NR | Good |
| Aekplakorn, 2019268 | RCT; primary care units in 8 provinces. Thailand | 30-65 years of age without a history of diabetes but with impaired glucose tolerance testing |
G1: lifestyle program with 17 sessions (34 PCUs, 1,030 total) G2: Usual care with one-time education program (34 PCUs, 873 total) | 2 |
G1: 50.9 (6.3) G2: 50.8 (6.5) |
G1: 809 (78.5%) G2: 708 (81.1%) | NR | NR |
G1: 97.1 (12.5) G2: 97.9 (12.3) |
G1: 26.7 G2: 27.3 | NR | Fair |
|
Bhopal, 201436 Welsh, 2016220 The Prevention of Diabetes and Obesity in South Asians (PODOSA) study | RCT; 2 National Health Service regions in Scotland | Indian or Pakistani adults aged 35+ y with IGT or IFG, no diagnosis of DM (other than gestational DM), and waist 90+ cm (men) or 80+ cm (women) |
G1: Lifestyle intervention with family support and visits to dietician (n=85) G2: Standardized advice with family support (n=86) | 3 |
G1: 52.8 (10.2) G2: 52.2 (10.3) |
G1: 46 (44) G2: 47 (45) |
G1: 85 (100) G2: 86 (100) | NR |
G1: 104.4 (10.8) G2: 104.4 (10.8) |
G1: 30.6(5.0) G2: 30.5 (4.6) |
G1: 136.9 (21.8) G2: 137.0 (19.7) G1: 82.7 (12.5) G2: 83.5 (10.7) Current tobacco use G1:6 (7) G2: 5 (6) | Fair |
|
Block, 2015205 Alive-PD | RCT; Ambulatory care health care delivery system in CA, U.S. | Adults aged 30-69 y with IFG or HbA1c in prediabetes range, and BMI of 27+ kg/m2 (non-Asians) or 25+ kg/m2 (Asians) |
G1: Alive-PD behavioral intervention for diabetes prevention delivered via the Web, Internet, mobile phone, and automated phone calls (n=163) G2: Usual care (n=176) | 0.5 |
G1: 54.9 (9.1) G2: 55.0 (8.8) |
G1: 54 (30.7) G2: 52 (31.9) |
G1: 56 (31.8) G2:54 (33.1) |
Overall 5.6 (0.3) G1: 5.6 (0.3) G2: 5.6 (0.3) |
Overall 109.9 (8.4) G1: 110.1 (8.6) G2: 109.6 (8.3) |
G1: 31.2 (4.3) G2: 31.1 (4.5) |
G1: 130.4 (14.5) G2: 130.5 (15.0) G1: 82.6 (8.7) G2: 82.0 (8.1) NR | Fair |
|
Davies, 201686 Gray, 2016118 Let’s Prevent Diabetes | Cluster RCT; 44 general practices in Leicestershire, U.K. | Adults aged 40-75 (White European) or 25-75 (South Asian) y with screen-detected prediabetes (IFG and/or IGT) |
G1: Let’s Prevent Diabetes lifestyle intervention (n=447) G2: Usual care (all received booklet with DM information) (n=433) | 3 |
G1: 63.9 (7.6) G2: 63.9 (7.9) |
G1:36.9 (NR) G2:35.8 (NR) |
G1: 70 (16.2) G2: 70 (15.7) |
G1: 6.1 (0.4) G2: 6.1 (0.4) |
G1: 102.6 (12.6) G2: 100.8 (12.6) |
G1:32.0 (5.2) G2:33.1 (5.8) |
G1: 147.9 (20.7) G2:147.7 (17.7) G1:86.6 (11.0) G2:86. 2(10.6) G1:38 (8.5) G2:22 (5.1) | Fair |
|
Diabetes Prevention Program Research Group, 200280 Diabetes Prevention Program Research Group, 2005119 Diabetes Prevention Program Research Group, 201297 DPP Diabetes Prevention Program Research Group, 2012237 Diabetes Prevention Program Research Group, 2009146 |
RCT (DPP) and open-label extension (DPPOS); 27 clinical centers throughout the U.S. Following double-blind phase, all participants were invited to participate in an open-labeled extension (DPPOS) | Adults aged 25+ y with IFG and IGT, no diagnosis of DM, and BMI 24+ kg/m2 (non-Asians) or 22+ kg/m2 (Asians) |
G1: Intensive lifestyle intervention* (n =1079; 910 enrolled in DPPOS) G2: Standard lifestyle recommendations plus metformin at a dose of 850 mg twice daily (n=1073; 924 enrolled in DPPOS) G3: Standard lifestyle recommendation plus placebo twice daily (n =1082; 932 enrolled in DPPOS) |
DPP: 2.8 DPPOS: 10-15† |
G1: 50.6 (11.3) G2: 50.9 (10.3) G3: 50.3 (10.4) |
G1: 734 (68.0) G2: 710 (66.2) G3: 747 (69.0) |
G1: 499 (46.2) G2:471 (43.9) G3: 496 (45.8) |
G1: 5.91 (0.51) G2:5.91 (0.50) G3: 5.91 (0.50) |
G1: 106.3 (8.1) G2: 106.5 (8.5) G3: 106.7 (8.4) |
G1:33.9 (6.8) G2:33.9 (6.6) G3:34.2 (6.7) | NR |
DPP: Good DPPOS: Fair |
|
Diabetes Prevention Program Research Group, 201579 Apolzan, 2019238 Diabetes Prevention Program Research Group, 201981 DPPOS | ||||||||||||
| Hellgren, 2014143 | RCT; Sweden | Adults aged 35–75 y with IGT and a FINDRISC questionnaire risk score >11. |
G1: Intensive intervention (focused only on physical activity) (n=19) G2: Basic intervention (n=18) G3: Usual care, with written and verbal information on IGT (n=15) | 1 |
G1: 66 (9) G2: 63 (10) G3: 68 (5) | 24 (53.3) | NR |
G1: 5.8 (NR) G2: 5.8 (NR) G3: 6.0 (NR) |
G1: 106.2 (9.0) G2: 108.0 (10.8) G3: 106.2 (10.8) |
G1: 30 (4) G2: 29 (4) G3: 30 (6) |
G1: 148 (19) G2: 82 (10) G3: NR G1: 144 (21) G2: 153 (17) G3: 145 (18) G1: 83 (9) G2: 83 (12) G3: 78 (7) | Fair |
| Hu, 2017215 | RCT; Rural areas in Hunan Province, China | Adults aged 60 y with prediabetes‡ |
G1: Synthetic intervention (n=214) G2: Standard health advice (n=220) | 1 |
G1: 69.2 (6.8) G2: 69.5 (6.3) |
G1: 121 (56.5) G2: 133 (60.5) | NR |
G1:5.7 (0.9) G2: 5.8 (1.1) |
G1: 111.0 (10.9) G2: 109.8 (8.8) |
G1: 23.5 (3.2) G2: 23.9 (3.7) | NR | Fair |
|
Katula, 2013144 Pedley, 2018257 Healthy Living Partnership (HELP PD) | RCT; community-based sites in North Carolina, U.S. | Volunteers with IFG and BMI 25-39 kg/m2 (eligibility criteria targeted representative sample in the community) |
G1: Lifestyle weight loss intervention adapted from DDPLI with exercise and reduction in caloric intake (n=151) G2: Enhanced usual care with nutrition counseling (n=150) | 2 | G1: 57.3 (10.1) G2: 58.5 (9) |
G1: 87 (57.6) G2: 86 (57.3) |
G1: 40 (26.5) G2: 39 (26.0) | NR |
G1: 105.4 (12.5) G2: 105.7 (10.0) |
G1: 32.8 (3.9) G2: 32.6 (4.1) | NR | Fair |
| Kosaka, 2005224 | RCT; Hospital medical center in Japan | Males with IGT and no previous history of diabetes |
G1: Lifestyle intervention (n=356) G2: Usual care (n=102) | 4 | NR | 0 (0) | NR | NR | NR |
G1: 24.0 (2.3) G2: 23.8 (2.1) |
G1: 123 (18) G2: 124 (17) G1: 78 (13) G2: 79 (11) NR | Fair |
| Kulkarni, 2018272 | RCT; outpatient medicine or endocrine clinic in one hospital system, India | 18 years or older, screened positive prediabetes, free of CVD |
G1: intensive lifestyle – standard lifestyle with use of a healthcare facilitator with weekly reminders and monthly phone calls (35) G2: intensive lifestyle and metformin – 500 BID (35) G3: advice on standard lifestyle modifications (standard care) (33) | 6 months |
G1: 45.3 (10.9) G2: 49.4 (9.2) G3: 49 (9.8) |
G1: 25 (71.4%) G2: 21 (60%) G3: 23 (69.7%) | NR |
G1: 6.13 G2: 6.1 G3: 6.05 |
G1: 109.4 G2: 108.9 G3: 109.3 |
G1: 29.3 G2: 28.1 G3: 28.5 |
G1: 123 (13) G2: 124 (10) G3: 124 (10) NR NR | Fair |
|
Kulzer, 2009112 Prevention of Diabetes Self-Management Program (PREDIAS) | RCT: Germany | Adults aged 20-70 y with IGT or IFG, or Diabetes Risk Score >10, or advisement of PCP, and BMI ≥26 kg/m2 |
G1: PREDIAS group lifestyle intervention based on the Diabetes Prevention Program (n=91) G2: Control (received the PREDIAS written information and patient materials (n=91) | 1 | 56.3 (10.1) | 78 (43) | NR |
G1: 5.7 (0.5) G2: 5.7 (0.6) | G1: 105.7 (12.4 G2: 105.5 (12.4) |
G1: 31 (4.7) G2: 32 (5.7) |
G1: 141.8 (18.6) G2: 139.1 (15.9) G1: 88.5 (10.5) G2: 87.3 (9.7) NR | Fair |
| Lindahl, 2009137 | RCT; Sweden | Adults recruited from community intervention program on CVD and diabetes, with IGT and BMI >27 kg/m2 |
G1: Intensive lifestyle with one-month residential stay (n=151 randomized, but only n=100 directly invited; 50 assigned as substitutes) G2: Usual care (n=150 randomized, but only n=100 directly invited; 50 assigned as substitutes) | 5 |
G1: 52.2 (9) G2: 53.5 (8.4) |
G1: 58 (69.9) G2: 52 (61.2) | NR | NR |
G1: 105.1 (23.8) G2: 111.4 (22.7) |
G1: 31.2 (3.1) G2: 30.2 (3.4) |
G1: 140.7 (19.3) G2: 141.3 (18.8) G1: 84.2 (10.0) G2: 85.7 (9.8) Daily smoker G1: 6 (7.2) G2: 7 (8.2) Ex-smoker G1: 29 (34.9) G2: 22 (25.9) | Fair |
|
Morey, 2012120 The Enhancing Fitness in Older Overweight Veterans with Impaired Glucose Tolerance (Enhanced Fitness) Trial | Controlled clinical trial; VA Medical Center, Durham, NC, U.S. | Adults aged 60+ y with IFG, no diagnosis of DM, and BMI 25- 45 kg/m2 |
G1: Counseling intervention focused on physical activity (n=180) G2: Usual care control (n=122) | 1 |
G1: 67.1 (6.3) G2: 67.7 (6.2) |
G1: 7 (3.9) G2: 3 (2.5) |
G1: 51 (28.3) G2: 39 (32.0) |
G1: 5.9 (0.4) G2: 5.9 (0.4) |
G1: 110.5 (6.95) G2: 110.6 (7.10) |
G1: 31.35 (3.75) G2: 30.97 (3.45) |
NR NR NR | Fair |
| Moungngern, 2018270 | RCT; outpatient department, Thailand | 18 years of age or older, 11-20% increased risk of developing T2DM in next 12 years, A1c 5.7-6.4 or FPG 100-125 or HDL <35 or triglycerides >250 of history of GDM or delivery of infant >4 kg |
G1: lifestyle program (nurse-managed health promotion program), group activities at 1, 2, 8 weeks (n=61) G2: routine self care (n=64) | 6 months |
G1: 55.9 (9.3) G2: 53.6 (9.8) |
G1: 47 (77%) G2: 46 (71.9%) | NR |
G1: 6 G2: 6 |
G1: 98 G2: 99 |
G1: 27.8 G2: 27.9 | NR | Fair |
|
O’Brien, 2017142 The Promotora Effectiveness Versus Metformin Trial (PREVENT-DM) | RCT; Health center in Philadelphia, PA, U.S. | Latinas aged ≥20 y with impaired fasting glucose and/or elevated HbA1c |
G1: Intensive group-based adaptation of the DPP lifestyle intervention delivered by promotoras (community healthcare workers (n=33) G2: Metformin 850 mg twice daily (n=29) G3: Standard care plus written educational materials on diabetes prevention (n=30) | 1 |
G1: 45.5 (12.3) G2: 45.8 (11.7) G3: 44.0 (13.6) | 92 (100) | 92 (100) |
G1: 5.9 (0.2) G2: 6.0 (0.2) G3: 5.9 (0.3) |
G1: 97.5 (7.5) G2: 94.6 (10.1) G3: 96.0 (10.7) |
G1: 34.4 (7.9) G2: 33.2 (5.5) G3: 32.2 (5.7) |
G1: 118.4 (13.9) G2: 122.2 (19.8) G3: 118.3 (17.6) G1: 74.5 (9.8) G2: 75.9 (10.2) G3: 73.3 (9.0) NR | Fair |
| Oldroyd, 2001212 | RCT; Hospital clinical research facility Newcastle upon Tyne, U.K. | Adults aged 24–75 y with IGT |
G1: Behavioral intervention (n=39) G2: Control (n=39) | 0.5 |
G1: 58.2 (NR) G2: 57.5 (NR) |
G1: 19 (54) G2: 10 (32) | NR |
G1: 5.8 (0.7) G2: 5.9 (0.5) |
G1: 108.0 (16.2) G2: 111.6 (16.2) |
G1: 30.4 (5.6) G2: 29.9 (4.9) |
G1: 137.2 (19.9) G2: 132.8 (16.4) G1: 77.0 (12.6) G2: 75.5 (9.8) NR | Fair |
|
Pan, 1997225 Li, 2008226 Li, 2014227 Gong, 2019228 China Da Qing Diabetes Prevention Outcomes Study (CDQDPOS) | Cluster RCT; Health care clinics in Da Qing, China | Adults aged >25 y with IGT |
G1: Combined 6-year lifestyle (diet, exercise, or diet + exercise) intervention: (n=438) G2: Control (n=138) | 30-year followup |
G1: 44.7 (SE 0.4) G2: 46.6 (SE 0.8) |
G1: 205 (47) G2:59 (43) | NR | NR |
G1: 100.8 (SE 14.4) G2: 99.4 (SE 14.4) |
G1: 25.6 (4.0) G2: 26.2 (3.8) |
G1: 131.9 (24.3) G2: 133.4 (26.0) G1: 87.0 (14.1) G2: 87.8 (15.4) G1: 169 (39) G2: 69 (50) | Fair |
| Penn, 2009264 | RCT; Hospital clinical research facility Newcastle upon Tyne, U.K. | Adults ages 40+ y with IGT, no previous diagnosis of DM, and BMI >25 kg/m2 |
G1: Individual behavioral intervention (n=51) G2: Usual care and standard health promotion advice (n=51) | Mean 3.1 |
G1: 56.8 (40-72) G2: 57.4 (38-74) |
G1: 30 (58.8) G2: 31 (60.8) | NR | NR |
G1: 102.6 (10.8) G2: 104.4 (9.0) |
G1: 34.1 (5.5) G2: 33.5 (4.6) | NR | Fair |
| Ramachandran, 2006234 Indian Diabetes Prevention Programme | RCT; India | Adults aged 35-55 y with IGT and no previous diagnosis of DM |
G1: Lifestyle Intervention (n=133) G2: Metformin (n=133) G3: Lifestyle Intervention + Metformin (n=129) G4: Standard health care advice (n=136) | 3 |
G1: 46.1 (5.7) G2: 45.9 (5.9) G3: 46.3 (5.7) G4: 45.2 (5.7) |
G1: 29 (21.8) G2:26 (19.5) G3: 24 (18.6) G4: 32 (23.5) | NR |
G1: 6.1 (0.5) G2: 6.2 (0.6) G3: 6.2 (0.6) G4: 6.2 (0.5) |
G1: 97.2 (12.6) G2: 97.2 (14.4) G3: 97.2 (14.4) G4: 99.0 (14.4) |
G1: 25.7 (3.3) G2: 25.6 (3.7) G3: 25.6 (3.3) G4: 26.3 (3.7) |
G1:121.5 (14.4) G2: 120.7 (15.9) G3: 122.4 (14.3) G4: 124.1 (16.0) G1: 74.4 (8.1) G2: 74.4 (9.2) G3: 74.9 (8.1) G4: 76.2 (8.6) G1: 29 (21.8) G2: 23 (17.3) G3: 27 (20.9) G4: 36 (26.5) | Fair |
|
Saito, 201187 ZPLS | RCT; 38 hospitals and clinics in Japan | Japanese adults aged 30-60 y with IFG, no DM diagnosis, and BMI ≥24 kg/m2 |
G1: Frequent intervention (received individual instructions and followup support for lifestyle modification 9 times over 36 months) (n=311) G2: Control group (received individual instructions and followup support for lifestyle modification 4 times over 12 months). (n=330) | 3 |
G1: 50 (44-54) G2: 48 (41-54) Median and IQR |
G1: 87 (28) G2: 96 (29) | NR |
G1: 5.4 (0.4) G2: 5.4 (0.4) |
G1: 108 (8) G2: 107 (8) |
G1: 26.9 (2.6) G2: 27.1 (2.6) |
G1: 130 (16) G2: 131 (16) G1: 81 (11) G2: 81 (12) G1: 78 (25) G2: 92 (28) | Fair |
| Sakane, 2011266 | RCT; 32 community health care institutions and company clinics across Japan | Adults aged 30-60 with IGT who had not yet begun lifestyle modifications on their own |
G1: Repeated sessions of group and individual lifestyle modification intervention (n=152) G2: one group session at baseline on healthy lifestyle and prevention of DM (n=152) | 3 |
G1: 51 (7) G2: 51 (6) | NR | NR | NR |
G1: 106.2 (9.0) G2: 109.8 (9.0) |
G1: 24.8 (3.6) G2: 24.5 (3.2) | NR | Fair |
|
Sakane, 2015140 The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) | Cluster RCT; 17 community and company healthcare divisions across Japan | Adults aged 25-60 y with IFG but no diagnosis of diabetes |
G1: 1-year telephone-delivered lifestyle support intervention (n=1,240) G2: Control (n=1,367) | Median 4.2 |
G1: 48.9 (7.8) G2: 48.9 (7.5) |
G1: 217 (17.5) G2: 217 (15.9) | NR | NR | Median: 106.2 |
G1: 24.4 (3.2) G2: 24.3 (3.1) |
NR NR NR | Fair |
|
Tuomilehto, 2001232 Uusitupa, 2009233 Finnish Diabetes Prevention Study (FDPS) | RCT; Finland | Adults aged 40-65 y with IGT, no diagnosis of diabetes, and BMI > 25 kg/m2 |
Original Study: G1: physical activity, weight reduction and dietary counseling intervention (n=265) G2: General diet & exercise (n=257) 10-y followup study: G1: same as above (n=257) G2: Same as above (n=248) |
Original study: mean 3.2 10-y followup study: mean 10.6 y |
Original study G1: 55 (7) G2: 55 (7) 10-y followup study G1: 55.4 (7.3) G2: 55.0 (6.9) |
Original study G1: 174 (65.7) G2: 176 (68.5) 10-year followup study G1: 169 (65.8) G2: 170 (68.5) | NR | NR |
Original study G1: 109 (14) G2: 110 (13) 10-year followup study G1: 109.8 (14.4) G2: 111.6 (12.6) |
Original study G1: 31.3 (4.6) G2: 31.0 (4.5) 10-y followup study G1: 31.4 (4.6) G2: 31.2 (4.5) |
Original study G1: 140 (18) G2: 136 (17) G1: 86 (9) G2: 86 (10) NR 10-y followup study: G1: 139.6 (17.7) G2: 136.2 (17.4) G1: 85.7 (9.4) G2: 85.6 (10.0) G1: 18 (7.0) G2: 18 (7.3) | Fair |
| Van Name, 2016141 | RCT; Community Health Center in New Haven, CT, U.S. | Women aged 18 and 65 y with at least one DM risk factor and prediabetes |
G1: Intensive Lifestyle Intervention (modified DPP) (n=65) G2: Usual care (n=65) | 1 |
G1: 43.8 (10.8) G2: 43.0 (9.7) | 122 (100) | 127 (98) |
G1: 5.8 (0.36) G2: 6.0 (0.33) |
G1: 102.6 (9.5) G2: 101.5 (11.1) |
G1: 35.4 (8.5) G2: 35.2 (7.3) |
G1: 119.1 (19.0) G2: 123.0 (16.7) G1: 77.3 (11.3) G2: 79.8 (11.0) NR | Fair |
|
Wong, 2013273 Wong, 2018274 | RCT; Community Health Project Hong Kong | Chinese professional drivers who were identified as pre-diabetics within last 3 months, had a mobile phone, no h/o DM |
G1: Short message service (SMS) intervention (54) G0: Control (usual care) (50) | 5 |
G1: 54.1 (6.1) G2: 55.2 (6.5) |
G1: 5 (9.3%) G2: 2 (4%) | NR | NR |
G1: 105.5 (7.6) G2: 106.2 (8.8) |
G1: 25.55 (2.94) G2: 26.25 (2.95) |
G1: 136.54 (15.88) G2: 133.9 (16.45) G1: 80.32 (10.67) G2: 80.86 (11.04) G1: 9 (17%) G2: 4 (8%) | Fair |
|
Yates, 2009138 The Prediabetes Risk Education and Physical Activity Recommendation and Encouragement (PREPARE) | RCT; Leicester, U.K. | Individuals with BMI ≥25 kg/m2 (or ≥23 kg/m2 if South Asian) and IGT, detected in ongoing population-based diabetes screening programs |
G3: Physical activity intervention without pedometer use (n=29) G2: Physical activity intervention with pedometer use (n=29) G1: Control (usual care) (n=29) | 1 |
G1: 66 (8) G2: 64 (7) G3: 65 (10) |
G1: 9 (31) G2: 9 (31) G3: 12 (41) |
G1: 4 (14) G2: 9 (31) G3: 9 (31) | NR |
G1: 100.8 (9.0) G2: 100.8 (10.8) G3: 102.6 (9.0) |
G1: 28.7 (4.8) G2: 29.5 (4.9) G3: 29.8 (4.4) |
G1: 139 (15) G2: 144 (17) G3: 141 (15) G1: 79 (10) G2: 82 (8) G3: 81 (10) G1: 1 (3) G2: 2 (7) G3: 5 (17) | Fair |
| Studies Evaluating Pharmacological Interventions (not including those that also evaluated lifestyle interventions from above) | ||||||||||||
|
Chiasson, 2002235 Chiasson, 2003236 STOP-NIDDM | RCT; Hospitals in 9 countries | Individuals aged 40-70 y with IGT, and BMI 25- 40 kg/m2 |
G1: Acarbose 100 mg 3x a day (n=714) G2: Placebo (n=715) | Mean 3.3 (1.2) |
G1: 54.3 (7.9) G2: 54.6 (7.9) |
G1: 353 (52) G2: 342 (50) |
G1: 18 (3) G2: 16 (2) | NR |
G1: 112.2 (8.9) G2: 112.5 (9.6) |
G1: 31.0 (4.3) G2: 30.9 (4.2) |
G1: 131.4 (16.3) G2: 130.9 (16.2) G1: 82.8 (9.4) G2: 82.0 (9.3) G1: 79 (12) G2: 99 (14) | Fair |
|
DeFronzo, 2011251 Espinoza, 2016252 Actos Now for Prevention of Diabetes Trial (ACT NOW) | RCT; 8 centers in the U.S. | Patients aged 18+ y with IGT, BMI ≥25 kg/m2 (>22 kg/m2 for Asian Americans), and at least one other risk factor for diabetes |
G1: Pioglitazone 30 mg/day for one month, increased to 45 mg/day (n=303) G2: Placebo (n=299) |
Median: 2.4 Mean: 2.2 | 52.3 (11.8) |
349 (58) OR 252 (41.9) |
G1: 69 (22.8) G2: 55 (18.3) |
G1: 5.5 (0.4) G2: 5.5 (0.4) |
G1: 105 (0.4) G2: 105 (0.4) Mg/dL |
G1: 33.0 (0.4) G2: 34.5 (0.4) |
G1: 127 (0.9) G2: 128 (0.9) G1: 74 (0.6) G2: 74 (0.6) NR | Fair |
|
DREAM Trial Investigators, 2006253 DREAM Trial Investigators, 2006254 DREAM Trial Investigators, 2008255 Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial | Multiple countries | Adults aged >30 years with IFG and/or IGT |
G1: Ramapril 15 mg/day (n=2623) G2: Placebo (n=2646) G3: Rosiglitazone 0.8mg/day (n=2635) G4: Placebo (n=2634) Patients randomized twice, to ramapril or placebo and rosiglitazone or placebo due to 2×2 factorial design | Median: 3 (Range: 2.5-4.7) |
G1:54.7 (10.9) G2:54.7 (10.9) G3:54.6 (10.9) G4:54.8 (10.9) |
G1: 1567 (59.7) G2: 1553 (58.7) G3: 1536 (58.3) G4: 1584 (60.1) | NR | NR |
G1 median (IQR): 106.3 (97.3-113.5) G2 median (IQR): 106.5 (97.3-115.3) G3: 104.4 (12.6) G4: 104.4 (12.6) |
G1:30.9 (5.6) G2:30.9 (5.7) G3:30.8 (5.6) G4:31.0 (5.6) |
G1: 136.1 (18.6) G2: 136.0 (18.1) G3: 135.9 (17.9) G4: 136.3 (18.8) G1: 83.4 (10.8) G2: 83.4 (10.8) G3: 83.3 (10.6) G4: 83.5 (10.9) Current or previous tobacco use G1: 1,158 (44.1) G2: 1,192 (45.0) G3: 1,157 (43.9) G4: 1,193 (45.3) | Good |
| Kaku, 2015218 | RCT; Multicenter, Japan | Japanese patients aged ≥20 y with suspected IGT |
G1: Sitagliptin 25g once daily (n=82) G2: Sitagliptin 50g once daily (n=77) G3: Placebo (n=83) | 0.15 (8 weeks) |
G1: 63.1(9.5) G2: 61.9 (9.3) G3: 61.9 (10.6) |
G1: 38 (46.3) G2: 32 (41.6) G3: 35 (42.2) | NR |
G1: 6.01 (0.25) G2: 6.02 (0.28) G3: 5.98 (0.27) |
G1: 105.5 (9.2) G2: 106.6 (10.1) G3: 105.7 (8.8) |
G1: 26 (3) G2: 25 (4) G3: 25 (3) |
NR NR NR | Fair |
| Kawamori, 2009256 | RCT; Multicenter, Japan | Adults aged 30-79 y with IGT |
G1: Voglibose 0.2 mg 3x/daily (n=897) G2: Placebo (n=883) |
48.1 weeks (SD 36.3 weeks) G1 45.0 weeks (34.7) G2 51.3 weeks (37.6) |
G1: 55.7 (9.1) G2: 55.7 (9.2) |
G1: 356 (39.7) G2: 351 (39.8) | NR | NR |
G1: 104.4 (0.55) G2: 105.3 (10.1) |
G1: 25.76 (3.70) G2: 25.89 (3.82) | NR | Good |
|
le Roux, 2017115 SCALE Obesity and Prediabetes Trial | RCT; 191 clinical research sites in 27 countries in Europe, North America, South America, Asia, Africa, and Australia | Adults aged 18+ y with prediabetes, no diagnosis of DM, and BMI ≥30 kg/m2 (≥27 kg/m2 with dyslipidaemia and/or hypertension) |
G1: Liraglutide (starting at 0.6 mg daily; weekly 0.6 mg increases to 3.0 mg with standardized lifestyle counseling (n=1505) G2: Placebo with standardized lifestyle counseling (n=749) | 3.3 (172 weeks) |
G1: 47.5 (11.7) G2: 47.3 (11.8) |
G1: 1141 (76) G2: 573 (77) |
G1: 249 (17) G2: 121 (16) |
G1: 5.8 (0.3) G2: 5.7 (0.3) |
G1: 99.0 (10.8) G2: 99.0 (9.0) |
G1: 38.8 (6.4) G2: 39.0 (6.3) |
G1: 124.7 (12.9) G2: 125.0 (12.8) G1: 79.4 (8.4) G2: 79.8 (8.3) NR | Fair |
|
Lindblad, 2011258 The Nepi ANtidiabetes StudY (NANSY) | RCT; Primary care, Sweden | Adults aged 40-70 y with IFG |
G1: glimepiride 1 mg/daily (n=136) G2: placebo (n=138) | Mean 3.7 |
G1: 60.4 (6.8) G2: 59.6 (6.7) |
G1: 48 (35.3) G2: 63 (45.7) | NR |
G1: 4.89 (0.54) G2: 4.87 (0.46) | NR |
G1: 29.9 (4.6) G2: 29.6 (4.2) |
G1: 144 (18) G2: 141 (18) G1: 82 (9.1) G2: 82 (9.2) G1: NR (18.0) G2: NR (21.3) | Fair |
| Lu, 2011259 | RCT; Beijing, China | Adults aged 40-80 y with screen-detected impaired glucose regulation, no diagnosis of DM, and BMI ≥19 kg/m2 |
G1: Patients with I-IGT: acarbose (50 mg three times daily) + lifestyle intervention; patients with I-IFG or IFG/IGT: metformin (0.25 g 3x daily) + lifestyle intervention (n=106) G2: Annual diabetes education (n=104) | 2 |
G1: 62.44 (9.16) G2: 64.72 (7.93) |
G1: 45 (47.4) G2: 41 (47.7) | NR |
G1: 5.91 (0.34) G2: 5.98 (0.43) |
G1: 106.0 (7.7) G2: 107.3 (9.2) |
G1: 27.07 (3.30) G2: 26.92 (3.65) |
G1: 129.65 (16.86) G2: 130.06 (19.54) G1: 78.95 (9.49) G2: 78.83 (10.79) NR | Fair |
| Pan, 2003246 | RCT; Five centers in the mainland of China | 35-70 years old with BMI =19-34. Screen-detected IGT (WHO criteria) |
G1: Acarbose (n=125) G2: Placebo (n=127) | 16 weeks |
G1: 53.4 (8.63) G2: 55.6 (8.31) |
G1: NR (60.8) G2: NR (59.1) | NR |
G1: 6.51 (0.72) G2: 6.61 (0.62) | NR |
G1: 25.6 (2.99) G2: 25.8 (3.22) |
G1:125.4 (14.1) G2: 126.8 (14.9) G1: 78 (7.8) G2: 78.1 (8.4) NR | Fair |
|
The NAVIGATOR Study Group, 2010260 The NAVIGATOR Study Group, 2010261 Currie, 2017262 Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial | RCT; 806 clinical centers in 40 countries | Adults with elevated FPG, IGT, and ≥1 CV risk factors (if aged 55+ y) or known CVD (if aged 50+) |
G1: Nateglinide 60 mg/3 times daily (n=4,645) G2: Placebo (n=4,661) G3: Valsartan 160 mg/once daily (n=4,631) G4: Placebo (n=4,675) Patients randomized twice, to nateglinide or placebo and valsartan or placebo due to 2×2 factorial design All patients also required to participate in lifestyle intervention program | Median: 5 y for incidence of diabetes |
G1: 63.7 (6.8) G2: 63.8 (6.9) G3: 63.7 (6.8) G4: 63.8 (6.8) |
G1: 2,368 (51.0) G2: 2,343 (50.3) G3: 2,314 (50.0) G4: 2,397 (51.3) |
G1 791 (17.0) G2 781 (16.8) (7.8) G3 782 (16.9) G4 790 (16.9) |
G1: 5.8 (0.45) G2: 5.8 (0.48) G3: 5.79 (0.47) G4 5.82 (0.46) |
G1: 109.8 (8.1) G2: 109.8 (8.3) G3: 109.8 (8.1) G4: 109.8 (8.1) |
G1: 30.5 (5.4) G2: 30.5 (5.4) G3: 30.4 (5.5) G4: 30.6 (5.3) |
G1: 139.8 (17.5) G2: 139.5 (17.4) G3: 139.4 (17.8) G4: 139.9 (17.1) G1: 82.6 (10.3) G2: 82.5 (10.2) G3: 82.5 (10.4) G4: 82.6 (10.1) G1: 519 (11.2) G2: 506 (10.9) G3: 518 (11.2) G4: 507 (10.8) | Good |
|
Nijpels, 2008263 DAISI | RCT; subjects invited from population register in Hoorn, the Netherlands | Adults aged 45-70 y with IGT, and HbA1c ≤7.0% |
G1: Acarbose 50 mg 3x daily (n=60) G2: Placebo (n=58) | 3 |
G1: 58.5 (7.9) G2: 56.5 (7.0) |
G1: 30 (50.8) G2: 29 (50.0) | NR |
G1: 5.9 (0.5) G2: 5.6 (0.6) |
G1: 118.8 (9.0) G2: 117.0 (10.8) |
G1: 28.4 (3.9) G2: 29.5 (3.8) |
NR NR G1: 15 (24.6) G2: 14 (23.3) | Fair |
|
Ramachandran, 2009265 IDPP-2 | RCT; Community-based, India | Asian Indian adults aged 35 to 55 y with IGT |
G1: Pioglitazone, 30 mg daily plus lifestyle modification (n=204) G2: Placebo plus lifestyle modification (n=203) | 3 |
G1: 45.1 (6.1) G2: 45.5 (6.3) |
G1: 26 (12.7) G2: 28 (13.8) | NR |
G1: 5.8 (0.4) G2: 5.8 (0.4) |
G1: 100.8 (12.6) G2: 102.6 (10.8) |
G1: 26.0 (3.5) G2: 26.2 (3.3) |
G1: 117.7 (10.8) G2: 117.9 (11.1) G1: 75.4 (10.9) G2: 75.6 (11.5) G1: 37 (18.1) G2: 47 (23.2) | Fair |
|
Weber, 2016222 Gokulakrishnan, 2017223 Diabetes Community Lifestyle Improvement Program (D-CLIP) | RCT; Community-based recruitment in Chennai, India | Adults aged 20-65 y with prediabetes and BMI 23 to <27.5 kg/m2 kg/m2 (overweight) or ≥ 27.5 (obese) and/or waist circumference ≥90cm (men) or ≥80cm (women) |
G1: Stepwise intervention of adapted DPP lifestyle classes plus metformin 500 mg twice daily at 4 months if at high risk of developing diabetes (n=283) G2: Standard of care (n=295) |
3 Mean 2.54 (range 4-48 months) |
44.4 (9.3) G1: 44.8 (9.0) G2: 44.0 (9.5) |
212 (36.8) G1: 102 (36.0) G2: 110 (37.5) | NR |
6.0 (0.5) G1: 6.0 (0.5) G2: 6.0 (0.5) |
Overall 102.6 (9.0) G1: 102.6 (9.0) G2: 102.6 (9.0) |
27.9 (3.7) G1: 27.9 (3.7) G2: 27.8 (3.7) | NR | Fair |
|
Zinman, 2010267 CAnadian Normoglycemia Outcomes Evaluation trial (CANOE) | RCT; Clinics in Ontario, Canada | Residents of Ontario Canada aged 18-75 y with >1 diabetes risk factor with screen-detected IGT |
G1: rosiglitazone 2 mg and metformin 500 twice daily and lifestyle intervention (n=103) G2: placebo and lifestyle intervention (n=104) |
3.9 (3.0-4.6 y) Median (IQR) |
G1: 50.0 (44.0-61.0) G2: 55.0 (46.0-61.0) Median (IQR) |
G1: 67 (65.0) G2: 71 (68.3) |
G1: 26 (25.3) G2: 27 (26) | NR |
G1: 97.2 (90.0-104.4) G2: 97.2 (90.0-106.2) Median (IQR) |
G1: 31.3 (27.1-35.7) G2: 32.0 (28.3-36.8) Median (IQR) |
G1: 130.0 (115.5-139.0) G2: 127.5 (118.0-140.8) G1: 80.0 (74.5-87.5) G2: 81.8 (75.3-87.5) Median (IQR) G1: 6 (5.8) G2: 10 (9.6) | Good |
- *
Following the DPP double-blinded phase, participants were unmasked to their treatment assignments and placebo was stopped. All participants, including the origional intensive lifesstyle group were offered a group-administered version of the 16-session lifestyle curriclum. Those previously assigned to metformin continued to receive metforming 850 mg twice daily, unmasked, as appropriate (unless there were safety concerns or they developed diabetes and required management by their own physician).
- †
Followup varies by outcome, although most open-label DPPOS analyses were conducted 10-15 years from randomization (or 7-12 years after participants were unblinded).
- ‡
Three groups: (1) IFG group: fasting plasma glucose of 6.1–7.0 mmol/L (110–126 mg/dL) and a 2-h post-glucose load of <7.8 mmol/L (140 mg/dL); (2) IGT group: fasting plasma glucose of 6.1 mmol/L (110 mg/dL) and a 2-h post-glucose load of 7.8–11.1 mmol/L (140–200 mg/dL); (3) IFG+IGT group.
Abbreviations: ACT NOW=Actos Now for Prevention of Diabetes; BMI=body mass index; BP=blood pressure; CA=California; CDQDPOS=China Da Qing Diabetes Prevention Outcomes Study’ CV=cardiovascular; CVD=cardiovascular disease; D-CLIP=Diabetes Community Lifestyle Improvement Program; DAISI=Dutch acarbose intervention study in persons with impaired glucose tolerance; DM=diabetes mellitus; DPP=Diabetes Prevention Program; DDPLI=Diabetes Prevention Program lifestyle intervention; DPPOS=Diabetes Prevention Program Outcomes Study; DREAM=Diabetes Reduction Assessment with ramipril and rosiglitazone Medication; FDPS=Finnish Diabetes Prevention Study; FINDRISC=Finnish Diabetes Risk Score; FPG=fasting plasma glucose; G=Group; GDM=gestational diabetes mellitus; HbA1c/HBA1c=hemoglobin A1c; HDL=high density lipoprotein; h/o=history of; IFG=impaired fasting glucose; IGT=impaired glucose tolerance; IQR=interquartile ratio; J-DOIT1=The Japan Diabetes Outcome Intervention Trial-1; NANSY=The Nepi ANtidiabetes StudY; NAVIGATOR=Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research; NR=not reported; PCP=primary care physician; PODOSA=The Prevention of Diabetes and Obesity in South Asians; PREDIAS=Prevention of Diabetes Self-Management Program; PREPARE=The Prediabetes Risk Education and Physical Activity Recommendation and Encouragement; PREVENT-DM=The Promotora Effectiveness Versus Metformin Trial; RAPID=Reaching Out to Prevent Increases in Diabetes; RCT-randomized, controlled trial; SCALE=Satiety and Clinical Adiposity–Liraglutide Evidence; SD=standard deviation; STOP-NIDDM=Study TO Prevent Noninsulin-Dependent Diabetes Mellitus; T2DM=type 2 diabetes mellitus; U.K.=United Kingdom; U.S.=United States; y=year; YDPP=YMCA diabetes prevention program; ZPLS=Zensharen Study for Prevention of Lifestyle Diseases.
Appendix E Table 5Mortality Results From Trials Evaluating Interventions for People With Prediabetes (KQ 4)
|
Source First Author, Year Trial Name |
G1 (N) G2 (N) | Followup (y) |
Mortality G N (%), or G1% vs. G2%; HR (95% CI) |
|---|---|---|---|
|
Diabetes Prevention Program Research Group, 200280 Diabetes Prevention Program Research Group, 2005119 Diabetes Prevention Program Research Group, 201297 DPP |
G1: Intensive lifestyle intervention (n =1079) G2: Standard lifestyle recommendations plus metformin at a dose of 850 mg twice daily (n=1073) G3: Standard lifestyle recommendation plus placebo twice daily (n =1082) | 3.2 |
All-cause deaths (N/100 person years of followup) G1: 0.10 G2: 0.20 G3: 0.16 No significant difference between groups CVD Related Deaths G1:2 G2:1 G3:4 |
| Hellgren, 2014143 |
G1: Intensive physical activity intervention (n=19) G2: Basic intervention (n=18) G3: Usual care (written and verbal information on IGT (n=15) | 1 | One person died from causes not related to the study (group in which the person was assigned is unclear) |
| Juul, 2016145 |
G1: Brief theory-based health promotion intervention (n=63) G2: Control (n=64) | 1 | No deaths during the study period |
|
Morey, 2012120 The Enhancing Fitness in Older Overweight Veterans with Impaired Glucose Tolerance (Enhanced Fitness) Trial |
G1: Counseling intervention focused on physical activity (n=180) G2: Usual care control (n=122) | 1 |
GI: 2 (1.1) G2:1 (0.8) |
|
Pan, 1997225 Li, 2008226 Li, 2014227 Gong, 2019228 China Da Qing Diabetes Prevention Outcomes Study (CDQDPOS) |
G1: Combined 6-year lifestyle (diet, exercise, or diet + exercise) intervention: (n=438) G2: Control (n=138) | 20, 23, 30 |
20-year followup: All-cause mortality: 25% vs. 29%; HR, 0.96 (0.65 to 1.41) CVD mortality: 12% vs. 17%: HR, 0.83 (0.48 to 1.40) 23-year followup: All-cause mortality: 28% vs.38%; HR, 0.71 (0.51 to 0.99) Women: 15% vs. 29%; HR, 0.46 (0.24 to 0.87) Men: 40% vs. 46%; HR, 0.97 (0.65 to 1.46) CVD mortality: 12% vs. 20%; HR, 0.59 (0.36 to 0.96) Women: 6% vs. 17%; HR, 0.28 (0.11 to 0.71) Men: 17% vs. 22%: HR, 0.91 (0.50 to 1.65) 30-year followup: All-cause mortality: 46% vs. 56%; HR, 0.74 (0.61 to 0.89) Women: 24% vs. 41%; HR, 0.59 (0.38 to 0.91) Men: 58% vs. 66%; HR, 0.85 (0.66 to 1.09) CVD mortality: 22% vs. 30%; HR, 0.67 (0.48 to 0.94) Women: 13% vs. 20%; HR, 0.61 (0.36 to 1.02) Men: 27% vs. 35%; HR, 0.73 (0.47 to 1.12) |
|
Ramachandran, 2006234 Indian Diabetes Prevention Programme |
G1: Lifestyle Intervention (n=133) G2: Metformin (n=133) G3: Lifestyle Intervention + Metformin (n=129) G4: Control (n=136) | 3 |
G1: 1 (0.8) G2: 0 (0) G3: 1 (0.8) G4: 1 (0.7) |
|
Saito, 201187 ZPLS |
G1: Frequent lifestyle modification (9 sessions over 3y) (n=311) G2: Control (4 lifestyle modification sessions over 1yr) (n=330) | 3 |
G1: 1 (0.3) G2: 0 (0) |
|
Tuomilehto, 2001232 Uusitupa, 2009233 Finnish Diabetes Prevention Study (FDPS) |
G1: physical activity, weight reduction and dietary counseling intervention (n=257) G2: General diet & exercise (n=248) | 10.6 |
G1: 6 (2.2 per 1000 person years) G2: 10 (3.8 per 1000 person years) HR, 0.57 (0.21-1.58) |
|
DREAM Trial Investigators, 2006253 DREAM Trial Investigators, 2006254 DREAM Trial Investigators, 2008255 Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial |
G1: Ramapril 15 mg/day (n=2623) G2: Placebo (n=2646) G3: Rosiglitazone 0.8mg/day (n=2635) G4: Placebo (n=2634) Patients randomized twice, to ramapril or placebo and rosiglitazone or placebo (2×2 factorial design) | 3 |
All-cause mortality: G1 vs. G2 1.2% (31/2623) vs. 1.2% (32/2646) HR, 0.98 (0.60 to 1.61) G3 vs. G4 1.1% (30/2635) vs. 1.3% (33/2634) HR, 0.91 (0.56 to 1.49) CVD mortality: G1 vs. G2 0.5% (12/2623) vs. 0.4% (10/2646) HR, 1.21 (0.52 to 2.80) G3 vs. G4 0.5% (12/2635) vs. 0.4% (10/2634) HR, 1.20 (CI 0.52 to 2.77) |
| Kawamori, 2009256 |
G1: Voglibose 0.2 mg 3x/daily (n=897) G2: Placebo (n=883) | 0.9 |
G1: 6 (0.7) G2: 0 (0) |
|
le Roux, 2017115 SCALE Obesity and Prediabetes Trial |
G1: Liraglutide (starting at 0.6 mg daily; weekly 0.6 mg increases to 3.0 mg with standardized lifestyle counseling (n=1505) G2: Placebo with standardized lifestyle counseling (n=749) | 3.3 |
All-cause mortality: G1: 2 (0.1) G2: 2 (0.3) CVD mortality: G1: 1 (0.1) G2: 0 (0) |
|
Lindblad, 2011258 The Nepi ANtidiabetes StudY (NANSY) |
G1: glimepiride 1 mg/daily (n=136) G2: placebo (n=138) | 3.7 |
All-cause mortality: G1: 5 (3.7) G2: 2 (1.4) CVD mortality: G1: 1 (0.7) G2: 2 (1.4) |
|
The NAVIGATOR Study Group, 2010260 The NAVIGATOR Study Group, 2010261 Currie, 2017262 Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial* |
G1: Nateglinide 60 mg/3 times daily (n=4645) G2: Placebo (n=4661) G3: Valsartan 160 mg/once daily (n=4631) G4: Placebo (n=4675) | 6 |
All-cause mortality G1 vs. G2: 6.7% (310/4645) vs. 6.7% (312/4661) HR, 1.00 (0.85 to 1.17) G3 vs. G4: 6.4% (295/4631) vs. 7.0% (327/4675) HR, 0.90 (0.77 to 1.05) CVD mortality G1 vs. G2: 2.7% (126/4645) vs. 2.5% (118/4661) HR, 1.07 (0.83 to 1.38) G3 vs. G4: 2.8% (128/4631) vs. 2.5% (116/4675) HR, 1.09 (0.85 to 1.40) Renal mortality G3 vs. G4: 0.1% (4/4631) vs. 0.1% (4/4675) HR, 1.00 (0.25 to 3.98) |
|
Nijpels, 2018263 DAISI |
G1: Acarbose 50 mg 3x daily (n=60) G2: Placebo (n=58) | 3 |
G1: 1 (1.7) G2: 3 (5.2) |
|
Ramachandran, 2009265 IDPP-2 |
G1: Pioglitazone 30 mg daily plus lifestyle modification (n=204; 181 analyzed) G2: Placebo plus lifestyle (n=203;186 analyzed) | 3 |
G1: 2 (1.1) G2: 1 (0.5) |
|
Weber, 2016222 Gokulakrishnan, 2017223 Diabetes Community Lifestyle Improvement Program (D-CLIP) |
G1: Stepwise intervention of adapted DPP lifestyle classes plus metformin 500 mg twice daily at 4 months if at high risk of developing diabetes (n=283) G2: Standard of care (n=295) | 3 | No deaths during the study period |
- *
The NAVIGATOR Trial randomized participants twice, to nateglinide or placebo and valsartan or placebo using a 2×2 factorial design. All participants were also offered a lifestyle intervention program.
Abbreviations: CDQDPOS=China Da Qing Diabetes Prevention Outcomes Study; CI=confidence interval; CVD=cardiovascular disease; D-CLIP=Diabetes Community Lifestyle Improvement Program; DAISI=Dutch acarbose intervention study in persons with impaired glucose tolerance; DPP=Diabetes Prevention Program; DREAM=Diabetes Reduction Assessment with ramipril and rosiglitazone Medication; FDPS=Finnish Diabetes Prevention Study; G=Group; HR=hazard ratio; IDPP-2=Indian Diabetes Prevention Programme-2; IGT=impaired glucose tolerance; NANSY=The Nepi ANtidiabetes StudY; NAVIGATOR=Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research; SCALE=Satiety and Clinical Adiposity–Liraglutide Evidence; ZPLS=Zensharen Study for Prevention of Lifestyle Diseases.
Appendix E Table 6Cardiovascular Disease Events in Trials Evaluating Interventions for People With Prediabetes (KQ 4)
|
Source First Author, Year Trial Name |
G1 (N) G2 (N) | Followup, Years |
CVD Events G: N (%), or G1 vs. G2; HR (95% CI) |
|---|---|---|---|
|
Ackermann, 2015139 Reaching Out to Prevent Increases in Diabetes (RAPID) |
G1: Group-based YMCA DPP intervention (n=257) G2: Usual care plus brief counseling and information on community resources (n=252) | 1 |
Self-reported cardiovascular events* G1: 1 (0.5) G2: 2 (0.9) p=0.99 |
|
Diabetes Prevention Program Research Group, 200280 Diabetes Prevention Program Research Group, 2005119 Diabetes Prevention Program Research Group, 201297 DPP |
G1: Intensive lifestyle intervention (n=1,079) G2: Standard lifestyle recommendations plus metformin at a dose of 850 mg twice daily (n=1,073) G3: Standard lifestyle recommendation plus placebo twice daily (n=1,082) | 3.2 |
Composite nonfatal CVD events G1: 24 (2.2%); 9.7 events per 1,000 patient-years G2: 16 (1.5%); 5.2 events per 1,000 patient-years G3: 18 (1.7%); 7.3 events per 1,000 patient-years No significant differences between placebo and either of the two groups |
|
Morey, 2012120 The Enhancing Fitness in Older Overweight Veterans with Impaired Glucose Tolerance (Enhanced Fitness) Trial |
G1: Counseling intervention focused on physical activity (n=180) G2: Usual care control (n=122) | 1 | One person had a transient ischemic attack that resulted in a hospitalization, and one person was diagnosed with myocardial infarction. Unclear whether events were in intervention or usual care group.† |
| Oldroyd, 2001212 |
G1: Behavioral intervention group (n=39 randomized; 35 analyzed) G2: Control group (n=39 randomized; 32 analyzed) | 0.5 |
Incident severe ischemic heart disease G1: 1 (2.86) G2: 0 (0) |
|
Pan, 1997225 Li, 2008226 Li, 2014227 Gong, 2019228 China Da Qing Diabetes Prevention Outcomes Study (CDQDPOS) |
G1: Combined 6-year lifestyle (diet, exercise, or diet+exercise) intervention: (n=438) G2: Control (n=138) | 20, 30 |
20-year followup Incidence of any first CVD event‡ 41% vs. 44%; HR 0.98 (0.71 to 1.37) 30-year followup Incidence of CVD event 195 (44.5) vs, 80 (58); HR 0.74 (0.59 to 0.92) Women: 73 vs. 29; HR 0.69 (0.51 to 0.92) Men: 122 vs. 51; HR 0.80 (0.60 to 1.06) Stroke 156 (35.6) vs, 62 (44.9); HR 0.75 (0.59 to 0.96) Women: 55 (26.8) vs. 22 (37.3); HR 0.68 (0.48 to 0.96) Men: 101 (43.3) vs. 40 (50.6); HR 0.83 (0.61 to 1.11) Coronary heart disease 61 (13.9) vs, 26 (18.8); HR 0.73 (0.51 to 1.04) Women: 22 (10.7) vs. 7 (11.9); HR 0.92 (0.39 to 2.13) Men: 39 (16.7) vs. 19(24.1); HR 0.68 (0.43 to 1.10) Heart Failure 39 (8.9) vs. 16 (11.6); HR 0.71 (0.48 to 1.04) Women: 14 (6.8) vs. 6 (10.2); HR 0.60 (0.29 to 1.25) Men: 25 (10.7) vs. 10 (12.6); HR 0.81 (0.41 to 1.60) |
| Penn, 2009264 |
G1: Individual behavioral intervention (n=51) G2: Usual care and standard health promotion advice (n=51) | 3.1 |
Cerebral infarction G1: 1 (0.8) G2: 0 (0.0) |
|
Ramachandran, 2006234 Indian Diabetes Prevention Programme |
G1: Lifestyle intervention (n=133) G2: Metformin (n=133) G3: Lifestyle intervention+metformin (n=129) G4: Standard health care advice (n=136) | 3 |
CVD events (not defined): G1: 4 G2: 0 G3: 5 G4: 2 |
|
Sakane, 2015140 The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) |
G1: 1-year telephone-delivered lifestyle support intervention (n=1,240) G2: Control (n=1,367) | 5.5 |
Ischemic heart disease: G1: 1 (0.08) G2: 2 (0.15) Stroke: G1: 3 (0.24) G2: 2 (0.15) |
|
Tuomilehto, 2001232 Uusitupa, 2009233 Finnish Diabetes Prevention Study (FDPS) |
G1: lifestyle intervention with ≥5% weight loss goal, individualized dietary and exercise information (n=257) G2: general information about diet and exercise (n=248) | 10.6 |
Incident fatal and nonfatal CVD events based on hospitalization registry ICD codes (acute coronary events, coronary heart disease, stroke and hypertensive disease): G1: 22.9 per 1,000 person-years (57 events) G2: 22.0 per 1,000 person-years (54 events) HR 1.04 (0.72 to1.51) |
|
Chiasson, 2002235 Chiasson, 2003236 STOP-NIDDM |
G1: Acarbose (n=682) G2: Placebo (n=686) | 3.3 |
Major CVD event (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease): 2.2% (15/682) vs. 4.7% (32/686) HR 0.51 (0.28 to 0.95) |
|
DeFronzo, 2011251 Espinoza, 2016252 Actos Now for Prevention of Diabetes Trial (ACT NOW) |
G1: Pioglitazone 30 mg/day for one month, increased to 45 mg/day (n=303) G2: Placebo (n=299) | 2.4 |
CVD system events 9% (26/303) vs. 8% (23/299) Atypical chest pain 0.33% (1/303) vs. 1.34% (4/299) Cardiac arrhythmia 1.65% (5/303) vs. 0.67% (2/299) Coronary artery bypass/revascularization 0.66% (2/303) vs. 2.01% (6/299) Coronary artery disease without revascularization 0.66% (2/303) vs. 0.33% (1/299) New or worsening angina 1.98% (6/303) vs. 1.34% (4/299) New or worsening CHF 0.33% (1/303) vs. 0.33% (1/299) Nonfatal MI 0.66% (2/303) vs. 0.33% (1/299) Peripheral vascular disease with claudication or revascularization 1.98% (6/303) vs. 0.00% (0/299) TIA 0.33% (1/303) vs. 0.33% (1/299) Malignant hypertension 0.00% (0/303) vs. 0.33% (1/299) |
|
DREAM Trial Investigators, 2006253 DREAM Trial Investigators, 2006254 DREAM Trial Investigators, 2008255 Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial |
G1: Ramapril 15 mg/day (n=2,623) G2: Placebo (n=2,646) G3: Rosiglitazone 0.8mg/day (n=2,635) G4: Placebo (n=2,634) Patients randomized twice, to Ramipril or placebo and rosiglitazone or placebo due to 2×2 factorial design | 3 |
Cardiovascular composite events incidence§ G1 vs.G2 2.6% (69/2623) vs. 2.4% (64/2646); HR 1.09 (0.78 to 1.53) G3 vs. G4 2.9% (77/2635) vs. 2.1% (56/2634); HR 1.38 (CI 0.98 to 1.95) MI: G1 vs. G2 0.5% (14/2623) vs. 0.4% (11/2646); HR 1.29 (0.59 to 2.84) G3 vs. G4 0.6% (16/2635) vs. 0.3% (9/2634); HR 1.78 (0.79 to 4.03) Stroke: G1 vs. G2 0.2% (4/2623) vs. 0.3% (8/2646); HR 0.50 (0.15 to 1.66) G3 vs. G4 0.3% (7/2635) vs. 0.2% (5/2634); HR 1.40 (0.44 to 4.40) Congestive heart failure: G1 vs. G2 0.5% (12/2623) vs. 0.2% (4/2646); HR 3.06 (0.99 to 9.48) G3 vs. G4 0.5% (14/2635) vs. 0.1% (2/2634); HR 7.04 (1.60 to 31.0) New angina: G1 vs. G2 0.9% (24/2623) vs. 0.8% (20/2646); HR 1.21 (0.67 to 2.19) G3 vs. G4 0.9% (24/2635) vs. 0.8% (20/2634); HR 1.20 (CI 0.66 to 2.17) Cardiovascular death, MI, stroke: G1 vs. G2 1% (27/2623) vs. 1.1% (29/2646); HR 0.94 (0.56 to 1.59) G3 vs. G4 1.3% (33/2635) vs. 0.9% (23/2634); HR 1.43 (CI 0.84 to 2.44) |
|
le Roux, 2017115 SCALE Obesity and Prediabetes Trial |
G1: Daily liraglutide intervention with standardized lifestyle counseling (n=1,505) G2: Placebo with standardized lifestyle counseling (n=749) | 3.3 |
Nonfatal myocardial infarctions: G1: 3 (0.2%) G2: 1 (0.1%) Nonfatal strokes: G1: 2 (0.1%) G2: 2 (0.3%) |
|
The NAVIGATOR Study Group, 2010260 The NAVIGATOR Study Group, 2010261 Currie, 2017262 Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial‖ |
G1: Nateglinide 60 mg/3 times daily (n=4,645) G2: Placebo (n=4,661) G3: Valsartan 160 mg/once daily (n=4,631) G4: Placebo (n=4,675) | 6 |
Fatal or nonfatal myocardial infarction G1 vs. G2: 2.9% (135/4645) vs. 3.1% (143/4,661) HR 0.95 (0.75 to 1.20) G3 vs. G4: 3% (138 /4631) vs. 3% (140/4,675) HR 0.97 (0.77 to 1.23) Fatal or nonfatal stroke G1 vs. G2: 2.4% (111/4645) vs. 2.7% (126/4,661) HR 0.89 (0.69 to 1.15) G3 vs. G4: 2.3% (105/4631) vs. 2.8% (132/4,675) HR 0.79 (0.61 to 1.02) Hospitalization for unstable angina G1 vs. G2: 4.8% (222/4645) vs. 5.4% (254/4,661) HR 0.87 (0.73 to 1.05) G3 vs. G4: 5.2% (242/4631) vs. 5.0% (234/4,675) HR 1.02 (0.86 to 1.23) Hospitalization for heart failure G1 vs. G2: 1.8% (85/4645) vs. 2.1% (100/4,661) HR 0.85 (0.64 to 1.14) G3 vs. G4: 2% (91/4631) vs. 2% (94/4,675) HR 0.97 (0.72 to 1.29) Arterial revascularization G1 vs. G2: 7.1% (332/4,645) vs. 6.8% (315/4,661) HR 1.06 (0.91 to 1.24) G3 vs. G4: 6.8% (316/4,631) vs. 7.1% (331/4,675) HR 0.94 (0.80 to 1.10) Hospitalization for a cardiovascular reason G1 vs. G2: 19% (883/4,645) vs. 18.9% (882/4,661) HR 1.00 (0.91 to 1.09) G3 vs. G4: 19.1% (886/4,631) vs. 18.8% (879/4,675) HR 1.00 (0.91 to 1.10) |
|
Ramachandran, 2009265 IDPP-2 |
G1: lifestyle modification plus pioglitazone, 30 mg (n=204; 181 analyzed) G2: lifestyle modification plus placebo (n=203; 186 analyzed) | 3 |
Heart disease requiring hospitalization: G1: 2 (1.1%) G2: 1 (0.5%) |
|
Zinman, 2010267 CAnadian Normoglycemia Outcomes Evaluation trial (CANOE) |
G1: rosiglitazone 2 mg and metformin 500 BID and lifestyle intervention (n=103) G2: placebo and lifestyle intervention (n=104) | 3.9 |
Myocardial infarction: G1: 1 G2: 0 Heart failure: G1: 1 G2: 0 |
- *
No additional details provided, including categories or types of cardiovascular events elicited from participants.
- †
The events were considered adverse events possibly related to the increae in physical activity (per study authors).
- ‡
Defined as first nonfatal or fatal cardiovascular events including myocardial infarction, sudden death, stroke, or amputation; authors also defined myocardial infarction cases on the basis of ECG results obtained during the physical examination on study followup visits.
- §
Defined as first occurrence of CVD death, cardiac resuscitation, nonfatal myocardial infarction, stroke, revascularization procedure, new stable or unstable angina with documented ischemia, or heart failure.
- ‖
The NAVIGTOR Trial randomized participants twice to nateglinide or placebo and valsartan or placebo using a 2×2 factorial design. All participants were also offered a lifestyle intervention program.
Abbreviations: ACT NOW=Actos Now for Prevention of Diabetes Trial; CANOE=CAnadian Normoglycemia Outcomes Evaluation; CDQDPOS=China Da Qing Diabetes Prevention Outcomes Study; CI=confidence interval; CVD=cardiovascular disease; DPP=Diabetes Prevention Program; ECG=electrocardiogram; FDPS=Finnish Diabetes Prevention Study; G=group; HR=hazard ratio; ICD=International Classification of Diseases; IDPP-2=Indian Diabetes Prevention Programme-2; J-DOIT1=The Japan Diabetes Outcome Intervention Trial-1; KQ=key question; N=number; NAVIGATOR=Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research; RAPID=Reaching Out to Prevent Increases in Diabetes.
Appendix E Table 7Quality of Life, Renal Disease, and Other Health Outcome Results From Trials Evaluating Interventions for People With Prediabetes (KQ 4)
|
Source First Author, Year Trial Name |
Groups (N) Followup |
Health Outcome G1 N (%) G2 N (%) |
|---|---|---|
|
Davies, 201686 Gray, 2016118 Let’s Prevent Diabetes |
G1: Let’s Prevent Diabetes lifestyle intervention (n=447) G2: Usual care (all received booklet with DM information) (n=433) 3 years |
Quality of Life Score (15 dimensional), Median (IQR) G1 Baseline: 0.90 (0.82, 0.95) G1 36 months:0.91 (0.84, 0.96) G2 Baseline:0.91 (0.84, 0.96) G2 36 months: 0.89 (0.82, 0.95) Overall Mean Effect* 0.01 (95% CI, 0.001, 0.02) |
|
Diabetes Prevention Program Research Group, 200280 Diabetes Prevention Program Research Group, 2005119 Diabetes Prevention Program Research Group, 201297 DPP |
G1: Intensive lifestyle intervention (n =1079) G2: Standard lifestyle recommendations plus metformin at a dose of 850 mg twice daily (n=1073) G3: Standard lifestyle recommendation plus placebo twice daily (n =1082) 3.2 years |
Difference in Mean Changes from baseline in intervention group compared to placebo group (SD)† Short Form-6D, G1 vs. G2: 0.0084 (0.0041) vs. 0.0019 (0.0041); p<0.05‡ SF-36 Physical component summary (SD), G1 vs. G2: 1.57 (0.30) vs. 0.15 (0.30); p<0.01 SF-36 Mental component summary, G1 vs. G2: −0.29 (0.32) vs. 0.22 (0.32) SF-36 domain scores (SD), G1 vs. G2: Physical function: 3.58 (0.71) vs. 0.13 (0.71); p<0.01 Role Physical : 1.86 (0.99) vs. 1.32 (0.99) Body pain: 1.93 (0.78) vs. 0.50 (0.78); p<0.01 General health: 3.23 (0.66) vs. 0.06 (0.66); p<0.01 Vitality: 2.05 (0.77) vs. 0.09 (0.76); p<0.01 Social functioning: 0.97 (0.66) vs. 0.81 (0.66) Role emotional: 0.20 (0.95) vs. 0.78 (0.95) Mental health: −0.50 (0.57) vs. 0.32 (0.57) |
|
Diabetes Prevention Program Research Group, 2012237 Diabetes Prevention Program Research Group, 2009146 Diabetes Prevention Program Research Group, 201579 Apolzan, 2019238 Diabetes Prevention Program Research Group, 201981 DPPOS |
G1: Standard lifestyle recommendations plus 850 mg metformin twice daily for 3.2 y; then open label metformin for additional 7-8 y and offered original DPP lifestyle intervention (n=924) G2: Standard lifestyle recommendation plus placebo twice daily and offered original DPP lifestyle intervention (n=932) 15 years (double blind phase 3.2 years) |
Participants whose most recent HbA1c was ≥ 6.5%: Retinopathy: G1 vs. G3, RR 0.61 (0.37-1.01), p =0.05 Neuropathy: G1 vs. G3, RR 0.38 (0.19-0.75), p =0.01 Nephropathy: Incidence shown in figure only, difference between intervention groups and placebo not statistically significant |
|
Kulzer, 2009112 Prevention of Diabetes Self-Management Program (PREDIAS) |
G1: PREDIAS group lifestyle intervention based on the Diabetes Prevention Program (n=91) G2: Control (received the PREDIAS written information and patient materials (n=91) 1 year |
World Health Organization-Five Well-Being Index (WHO-5), change from baseline: G1: 1.4 (3.9), p=0.015 G2: 0.0 (4.2), p=0.901 Between group, p=0.101 |
|
Morey, 2012120 The Enhancing Fitness in Older Overweight Veterans with Impaired Glucose Tolerance (Enhanced Fitness) Trial |
G1: Counseling intervention focused on physical activity (n=180) G2: Usual care control (n=122) 1 year |
SF-36 General Health G1 Baseline: 61.39 (39.40) G1 3 Months: 59.84 (42.59) G1 12 Months: 58.12 (42.29) G2 Baseline: 65.78 (39.52) G2 3 Months: 66.37 (42.75) G2 12 Months: 61.68 (41.82) P =0.92 SF-36 Physical Function G1 Baseline: 62.94 (20.97) G1 3 Months: 63.97 (21.30) G1 12 Months: 62.52 (21.79) G2 Baseline: 66.88 (20.60) G2 3 Months: 67.08 (19.86) G2 12 Months: 66.24 (20.91)P =0.09 |
|
le Roux, 2017115 SCALE Obesity and Prediabetes Trial |
G1: Liraglutide (starting at 0.6 mg daily; weekly 0.6 mg increases to 3.0 mg with standardized lifestyle counseling (n=1505) G2: Placebo with standardized lifestyle counseling (n=749) 3.3 year |
SF-36 Physical component summary, mean change from baseline score (SD) G1: 3.1 (7.3) G2: 2.6 (7.6) RD, 0.9 (0.2 to 1.6) p=0.0156 SF-36 Mental component summary, mean change from baseline score (SD) G1: −0.5 (8.7) G2: −1.4 (9.2) RD 0.8 (−0.1 to 1.6) p=0.08 |
|
The NAVIGATOR Study Group, 2010260 The NAVIGATOR Study Group, 2010261 Currie, 2017262 Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial |
G1: Nateglinide 60 mg/3 times daily (n=4645) G2: Placebo (n=4661) G3: Valsartan 160 mg/once daily (n=4631) G4: Placebo (n=4675) Patients randomized twice, to nateglinide or placebo and valsartan or placebo due to 2×2 factorial design 5 years |
NR End-stage renal disease (ESRD) G3: 5 (0.1) G4: 5 (0.1) HR, 0.96 (0.28 to 3.31) Amputations: G1: 1 (<0.1) G2: 6 (0.1) G3: 5 (0.1) G4: 2 (<0.1) |
|
Pan, 1997225 Li, 2008226 Li, 2014227 Gong, 2019228 China Da Qing Diabetes Prevention Outcomes Study (CDQDPOS) |
G1: Combined 6-year lifestyle (diet, exercise, or diet+exercise) intervention: (n=438) G2: Control (n=138) 30 years |
Composite Microvascular Disease§ G1: 76 (17.4) G2: 33 (23.9) HR, 0.65 (0.45 to 0.95) Women: 42 vs. 16; HR, 0.69 (0.37 to 1.32) Men: 34 vs. 17; HR, 0.61 (0.35 to 1.06) Retinopathy‖ G1: 56 (12.8) G2: 26 (18.8) HR, 0.60 (0.38 to 0.95) Women: 34 (16.6) vs. 13 (22.0); HR, 0.71 (0.34 to 1.48) Men: 22 (9.4) vs. 13 (16.4); HR, 0.50 (0.25 to 1.002) Nephropathy¶ G1: 16 (3.6) G2: 7 (5.1) HR, 0.68 (0.36 to 1.28) Women: 8 (3.9) vs. 1(1.7); HR, 2.18 (0.28 to 16.72) Men: 8 (3.4) vs. 6 (7.6); HR, 0.43 (0.18 to 1.04) Neuropathy# G1: 14 (3.2) G2: 7 (5.1) HR, 0.57 (0.24 to 1.36) Women: 4 (2.0) vs. 3 (5.1); HR, 0.35 (0.08 to 1.63) Men: 10 (4.3) vs. 4 (5.1); HR, 0.79 (0.21 to 2.95) |
- *
Adjusted for baseline value and clusters.
- †
Scores worsend from baseline in all groups for the SF-6D and SF-36 PCS and MCS; the decline for SF-6D and PCS was lower in the intensive lifestyle group than placebo or metformin groups but did not meet the minimally important difference of 3% (defined by authors).
- ‡
Difference between grous remains statisically significant when controlling for age, sex, race/ethnicity, baseline weight and physical activity, medical and psychiatric comorbidiy but magnitude is smalle: 0.009 (SD 0.14).
- §
Composite microvascular disease defined as an aggregate of retinopathy, nephropathy, or neuropathy.
- ‖
Retinopathy defined as a history of photocoagulation, blindness from retinal disease, or proliferative retinopathy.
- ¶
Nephropathy defined as a history of end stage renal disease, renal dialysis, renal transplantation, death from chronic kidney disease.
- #
Neuropathy defined as a history of lower extremity ulceration, gangrene, or amputation.
Abbreviations: CI=confidence interval; DM=diabetes mellitus; DPP=Diabetes Prevention Program; DPPOS=Diabetes Prevention Program; ESRD=end-stage renal disease; IQR=interquartile ratio; N=Number; NAVIGATOR=Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research; PREDIAS=Prevention of Diabetes Self-Management Program; SCALE=Satiety and Clinical Adiposity–Liraglutide Evidence; SD=standard deviation; U.K.=United Kingdom; VDT=Vibration Detection Threshold; WHO=World Health Organization.
Appendix E Table 8Mortality and Cardiovascular Event Outcomes Among Individuals With Newly Diagnosed Type 2 Diabetes (KQ 5)
|
First Author, Year Trial Name Country |
G1 (N) G2 (N) |
Mortality G1 vs. G2; HR (95% CI) |
CVD Events G1 vs. G2; HR (95% CI) |
|---|---|---|---|
|
Yang, 2013276 China |
G1: 75 G2: 75 | NR |
Myocardial Infarction 7-year followup (per protocol) G1: 1//75 (1.3%) G2: .1/75 (1.3%) RR, 1.0 (0.06 to 15.7) Transient Ischemic Attack 7-year followup (per protocol) G1: 0//75 (0%) G2: 2/75 (2.7%) RR, 2.0 (0.01 to 4.1) |
|
UKPDS Group 19981 UK Prospective Diabetes Study (UKPDS) U.K. |
G1: 2729 G2: 619 G3: 615 G4: 911 G5a: 1138 G5b: 896 |
Median 10.0-year followup G1 vs. G5a All-cause mortality: 18% vs. 19%; RR, 0.94 (0.80 to 1.10) Diabetes-related death: 10% vs. 11%; RR, 0.90 (0.73 to 1.11) Fatal myocardial infarction: 7.6% vs. 7.9%; RR, 0.94 (0,68 to 1.30) Fatal stroke: 1.6% vs.1.3%; RR, 1.17 (0.54 to 2.54) Sudden death: 0.88% vs. 1.6%; RR, 0.54 (0.24 to 1.21) Median 11.1-year followup G2 vs. G5b All-cause mortality: 22% vs. 21%; RR, 1.02 (0.82 to 1.27) Diabetes-related death: 12% vs.13%; RR, 0.92 (0.68 to 1.23) Fatal myocardial infarction: 9.0% vs. 8.9%; RR, 0.99 (0.64 to 1.56) Fatal stroke: 1.5% vs.1.3%; RR, 1.06 (0.34 to 3.30) Sudden death: 0.97% vs. 1.7%; RR, 0.57 (0.16 to 1.97) G3 vs. G5b All-cause mortality: 20% vs. 21%; RR, 0.91 (0.73 to 1.15) Diabetes-related death: 12% vs.13%; RR, 0.92 (0.69 to 1.24) Fatal myocardial infarction: 7.5% vs. 8.9%; RR, 0.82 (0,51 to 1.33) Fatal stroke: 2.6% vs.1.3%; RR, 1.90 (0.71 to 5.09) Sudden death: 1.1% vs. 1.7%; RR, 0.67 (0.21 to 2.16) G4 vs. G5b All-cause mortality: 20% vs. 21%; RR, 0.93 (0.76 to 1.14) Diabetes-related death: 12% vs.13%; RR, 0.90 (0.69 to 1.18) Fatal myocardial infarction: 8.7% vs. 8.9%; RR, 0.96 (0,63 to 1.43) Fatal stroke: 1.5% vs. 1.3%; RR, 1.13 (0.41 to 3.12) Sudden death: 0.99% vs. 1.7%; RR, 0.58 (0.19 to 1.70) |
Median 10.0-year followup G1 vs. G5a Myocardial infarction: 14% vs. 16%; RR, 0.84 (0.71 to 1.00) Stroke:5.4 % vs. 4.9%; RR, 1.11 (0.81 to 1.51) Median 11.1-year followup G2 vs. G5b Myocardial infarction: 16% vs. 18%; RR, 0.87 (0.68 to 1.12) Stroke: 5.3% vs. 5.2%; RR, 1.01 (0.65 to 1.58) G3 vs. G5b Myocardial infarction: 15% vs. 18%; RR, 0.78 (0.60 to 1.01) Stroke: 7.3% vs.5.2%; RR, 1.38 (0.52 to 2.08) G4 vs. G5b Myocardial infarction: 16% vs. 18%; RR, 0.87 (0.70 to 1.09) Stroke: 4.6% vs. 5.2%; RR, 0.86 (0.57 to 1.31) |
|
UKPDS Group, 1998277 UKPDS Metformin for overweight substudy U.K. |
G1: 342 G2: 411 |
10-year followup results (G1 vs. G2) All-cause mortality: 50/342 (14.6) vs. 89/411 (21.7); RR, 0.64 (0.45 to 0.91) Diabetes-related death: 28/342 (8.2) vs. (13.4) 55/411; RR, 0.58 (0.37 to 0.91) |
10-year followup results (G1 vs. G2) MI: 39 (11.4) vs. 73 (17.8); RR, 0.61 (0.41 to 0.89) Stroke: 12/342 (3.5) vs. 23/411 (5.6); RR, 0.59 (0.29 to 1.18) |
|
Holman, 2008278 UKPDS U.K. |
G1: 2729 G2: 342 G3: 1138 G4: 411 |
10-years post-trial monitoring results G1 vs. G3 All-cause mortality: 43% (1162/2729) vs. 47% (537/1138); RR, 0.87, (0.79 to 0.96) Diabetes-related death: 23% (618/2729) vs. 26% (297/1138); RR, 0.83 (0.73 to 0.96) G2 vs. G4 All-cause mortality: 44% (152/342) vs. 53% (217/411); RR, 0.73 (0.59 to 0.89) Diabetes-related death: 24% (81/342) vs. 29% (120/411); RR, 0.70 (0.53 to 0.92) |
10-years post-trial monitoring results G1 vs. G3 Myocardial infarction: 25% (678/2729) vs. 28% (319/1138); RR, 0.85 (0.74 to 0.97) Stroke: 9.5% (38/2729) vs. 10.2% (34/1138); RR, 0.91 (0.73 to 1.13) G2 vs. G4 Myocardial infarction: 24% (81/342) vs. 31% (126/411); RR, 0.67 (0.51 to 0.89) Stroke: 9.9% (34/342) vs. 10.2% (42/411); RR, 0.80 (0.50 to 1.27) |
|
Holman, 200892 UKPDS Group, 1998279 Hypertension in diabetes Study embedded in UKPDS |
G1: 758 G2: 390 Post-trial monitoring group (n=884) |
9-year followup G1 vs. G2 All-cause mortality: 17.7% (134/758) vs. 21.3% (83/390); RR, 0.82 (0.63 to 1.08) Diabetes-related death: 10.8% (82/758) vs. 15.9% (62/390) RR, 0.68 (0.49 to 0.94) Post-trial monitoring 10 years results G1 vs. G2 All-cause mortality: 49% (373/758) vs. 54% (211/390); RR, 0.89 (0.75 to 1.06) Diabetes-related death: 27% (203/758) vs. 31% (122/390) RR, 0.84 (0.67 to 1.05) |
9-year followup G1 vs. G2 Myocardial infarction: 14.1% (107/758) vs. 17.7% (69/390) RR, 0.79, (0.59 to 1.07) Stroke: 5.0% (38/758) vs. 8.7% (34/390); RR, 0.56 (0.35 to 0.89) Post-trial monitoring 10 years results G1 vs. G2 Myocardial infarction: 27% (205/758) vs. 29.5% (115/390); RR, 0.90 (0.71 to 1.13) Stroke: 12% (90/758) vs. 15% (58/390); RR, 0.77 (0.55 to 1.07) |
|
Davies, 200893 Khunti, 201294 DESMOND U.K. |
G1: 437 G2: 387 |
G1 vs. G2 All-cause mortality at 4-month: 0% (0/437) vs. 0.5% (2/387) RR, 0.18 (0.01 to 3.68) All-cause mortality at 8-months: 0.5% (2/437) vs. 1% (4/387) RR, 0.44 (0.08 to 2.40) All-cause mortality at 12-months: 0.5% (2/437) vs. 1.3% (5/387) RR, 0.35 (0.07 to 1.82) All-cause mortality at 3-yr f/u: 3.9% (15/437) vs. 2.5% (11/387) RR, 1.21 (0.56 to 2.60) | NR |
Abbreviations: CI=confidence interval; CVD=cardiovascular disease; DESMOND=Diabetes education and self management for ongoing and newly diagnosed programme; G=group; HR=hazard ratio; KQ=key question; NR=not reported; RR=relative risk; U.K.=United Kingdom; UKPDS=United Kingdom Prospective Diabetes Study; vs.=versus.
Appendix E Table 9Quality of Life Outcomes Among Individuals With Newly Diagnosed Type 2 Diabetes (KQ 5)
|
Source First Author, year Trial Name Country |
Groups N | Quality of Life |
|---|---|---|
|
Davies, 200893 Khunti, 201294 DESMOND U.K. |
G1: 437 G2: 387 |
Quality of life, WHOQOL-BREF Median score (IQR) (G1, n=299; G2, n=237) Overall satisfaction with quality of life: G1 3 years: 4.0 (4, 4) G2 3 years: 4.0 (4, 5) Model summary coefficient (95% CI): −0.04 (−0.17 to 0.08) p-value 0.48 Overall satisfaction with health: G1 3 years: 4.0 (3, 4) G2 3 years: 4.0 (3, 4) Model summary coefficient (95% CI): −0.01 (−0.20 to 0.18) p-value 0.94 Physical quality of life: G1 3 years: 26.0 (22, 29) G2 3 years: 25.5 (22,29) Model summary coefficient (95% CI): −0.15 (−0.84 to 0.55) p-value 0.68 Psychological quality of life: G1 3 years: 23.0 (20 to 25) G2 3 years: 23.0 (20 to 25) Model summary coefficient (95% CI): −0.10 (−0.61 to 0.42) p-value 0.71 Social quality of life: G1 3 years: 11.0 (9, 12) G2 3 years: 11.0 (10,12) Model summary coefficient (95% CI): 0.05 (−0.37 to 0.47) p-value 0.81 Environmental quality of life: G1 3 years: 31.0 (28,34) G2 3 years: 31.0 (28, 34) Model summary coefficient (95% CI): −0.01 (−0.67 to 0.65) p-value 0.98 No differences between groups in the WHOQOL-Brief at 4, 8, and 12-months f/u (data not shown) |
Abbreviations: CI=confidence interval; DESMOND=Diabetes education and self management for ongoing and newly diagnosed programme; IQR=interquartile range; N=Number; QoL=quality of life; U.K.=United Kingdom; WHOQOL-BREF=World Health Organization Quality of Life.
Appendix E Table 10Chronic Kidney Disease, Amputations, and Visual Impairment Outcomes Among Individuals With Newly Diagnosed Type 2 Diabetes (KQ 5)
|
Source First Author, Year Trial Name Country |
Groups N |
Chronic Kidney Disease G1 N (%) G2 N (%) HR (95% CI) |
Amputations G1 N (%) G2 N (%) HR (95% CI) |
Visual Impairment G1 N (%) G2 N (%) HR (95% CI) |
|---|---|---|---|---|
|
UKPDS Group 19981 U.K. Prospective Diabetes Study (UKPDS) U.K. |
G1: 2729 G2: 619 G3: 615 G4: 911 G5a: 1138 G5b: 896 |
10-year followup Renal Failure G1 vs. G5a: G1: 16 (0.6) G5a: 9 (0.8) RR, 0.73 (0.25 to 2.14) G2 vs. G5b: G2: 6 (0.2) G5b: 8 (0.9) RR, 1.09 (0.27 to 4.37) G3 vs. G5b: G3: 4 (0.7) G5b: 8 (0.9) RR, 0.72 (0.15 to 3.50) G4 vs. G5b: G4: 5 (0.5) G5b: 8 (0.9) RR, 0.61 (0.14 to 2.64) |
10-year followup G1 vs. G5a: G1: 27 (1.0) G5a: 18 (1.6) RR, 0.61 (0.28 to 1.33) G2 vs. G5b: G2: 5 (0.8) G5b: 15 (1.7) RR, 0.47 (0.12 to 1.77) G3 vs. G5b: G3: 5 (0.8) G5b: 15 (1.7) RR, 0.48 (0.13 to 1.80) G4 vs. G5b: G4: 15 (1.6) G5b: 15 (1.7) RR, 0.95 (0.37 to 2.45) |
10-year followup Retinal photocoagulation G1 vs. G5a: G1: 207 (7.6) G5a: 117 (10.3) RR, 0.71 (0.53 to 0.96) G2 vs. G5b: G2: 55 (8.9) G5b: 101 (11.3) RR, 0.77 (0.50 to 1.18) G3 vs. G5b: G3: 45 (7.3) G5b: 101 (11.3) RR, 0.63 (0.40 to 1.00) G4 vs. G5b: G4: 72 (7.9) G5b: 101 (11.3) RR, 0.67 (0.45 to 0.99) Vitreous Hemorrhage G1 vs. G5a: G1: 19 G5a: 10 RR, 0.77 (0.28 to 2.11) G2 vs. G5b: G2: 8 (1.3) G5b: 10 (1.1) RR, 1.14 (0.34 to 3.86) G3 vs. G5b: G3: 6 (1.0) G5b: 10 (1.1) RR, 0.73 (0.18 to 2.98) G4 vs. G5b: G4: 5 (0.5) G5b: 10 (1.1) RR, 0.48 (0.12 to 1.96) Blind in one eye G1 vs. G5a: G1: 78 (2.8) G5a: 38 (3.2) RR, 0.84 (0.51 to 1.40) G2 vs. G5b: G2: 21 (3.4) G5b: 36 (4.0) RR, 0.64 (0.41 to 1.70) G3 vs. G5b: G3: 15 (2.4) G5b: 36 (4.0) RR, 0.61 (0.27 to 1.34) G4 vs. G5b: G4: 29 (3.2) G5b: 36 (4.0) RR, 0.75 (0.39 to 1.43) Cataract extraction G1 vs. G5a: G1: 149 (2.8) G5a: 80 (3.2) RR, 0.76 (0.53 to 1.08) G2 vs. G5b: G2: 33 (5.3) G5b: 70 (7.8) RR, 0.67 (0.39 to 1.15) G3 vs. G5b: G3: 44 (7.2) G5b: 70 (7.8) RR, 0.91 (0.55 to 1.50) G4 vs. G5b: G4: 50 (5.5) G5b: 70 (7.8) RR, 0.68 (0.42 to 1.10) |
|
UKPDS Group, 1998277 UKPDS* Metformin for overweight substudy U.K. |
G1: 342 G2: 411 | NR |
Median followup 10.7 years G1 vs. G2 6/342 (1.8) vs. 9/411 (2.2); RR, 0.74 (0.19 to 2.89) |
Blindness in one eye G1 vs. G2 12/342 (3.5) vs. 13 (3.2); RR, 1.07 (0.38 to 2.99) |
|
Holman, 200892 UKPDS Group, 1998279 Hypertension in diabetes Study embedded in UKPDS |
G1: 758 G2: 390 Post-trial monitoring group (n=884) |
G1 vs. G2 Renal Failure 9-year followup 1.1% (8/758) vs. 1.8% (7/390) RR, 0.53 (0.15 to 2.21) Urinary albuminuria ≥50 mg/l At 3 years 18.3% (113/618) vs. 23.7% (75/317) RR, 0.77 (0.55 to 1.09) At 6 years 20.3% (110/543) vs. 28.5% (78/274) RR, 0.71 (0.51 to 0.99) At 9 years 28.8% (86/299) vs. 33.1% (55/166) RR, 0.87 (0.60 to 1.26) Urinary albuminuria ≥300 mg/l At 3 years 3.2% (20/618) vs. 5.7% (18/317) RR, 0.57 (0.25 to 1.29) At 6 years 5.3% (29/543) vs. 8.6% (24/274) RR, 0.61 (0.31 to 1.21) At 9 years 7.0% (21/299) vs. 6.6% (11/166) RR, 1.06 (0.42 to 2.67) |
9-year followup G1 vs. G2 1.1% (8/758) vs. 2.1% (8/390) RR, 0.51 (0.14 to 1.86) |
G1 vs. G2 Progression of retinopathy ≥2 steps At Median 1.5 years 20.2% (93/461) vs. 23.1% (56/243) RR, 0.88 (0.60 to 1.29) At Median 4.5 years 27.5% (113/411) vs. 36.7% (76/207) RR, 0.75 (0.55 to 1.02) At Median 7.5 years 34.0% (102/300) vs. 51.3% (78/152) RR, 0.66 (0.50 to 0.89) Deterioration in vision by ≥3 ETDRS lines Median 1.5 years 5.4% (31/575) vs. 6.8% (20/293) RR, 0.79 (0.39 to 1.62) Median 4.5 years 7.5% (39/523) vs. 8.9% (23/257) RR, 0.83 (0.44 to 1.59) Median 7.5 years 10.2% (34/332) vs. 19.4% (35/180) RR, 0.53 (0.30 to 0.93) |
Abbreviations: CI=confidence interval; ETDRS=Early Treatment Diabetic Retinopathy Study; G=group; HR=hazard ratio; KQ=key question; N=Number; NR=not reported; RR=relative risk; U.K.=United Kingdom; UKPDS=United Kingdom Prospective Diabetes Study; vs.=versus.
Appendix E Table 11Harms Reported in Included Trials of Interventions for People With Screen-Detected or Newly Diagnosed Type 2 Diabetes Reporting Harms (KQ 6)
|
Author, Year Trial Name Country |
Mortality G1 (N) G2 (N) HR (95% CI) |
Hypoglycemic Events Requiring Medical Attention G1 N (%) G2 N (%) HR (95% CI) |
All Cause Withdrawals G1 N (%) G2 N (%) HR (95% CI) |
Other Adverse Events G1 N (%) G2 N (%) HR (95% CI) |
|---|---|---|---|---|
|
Davies, 200893 Khunti, 201294 DESMOND U.K. | NR | NR |
G1 21/437 (4.8) G2 23/387 (5.9) RR, 0.81 (95% CI 0.45 to 1.44) | NR |
|
van den Donk, 201095 Janssen, 2009117 ADDITION-Netherlands | NR |
G1 1/255 (0.4) G2 0/243 (0) |
G1: 5/255 (2) G2: 2/243 (1) RR, 2.38 (0.47 to 12.16) | |
|
U.K. Prospective Diabetes Study (UKPDS) Group, 19981 U.K. |
Death from hypoglycemia G1 vs. G5a: G1: 1/2729 (0) G5a: 0/1138 (0) G2 vs. G5b: G2: 0/619 (0) G5b: 0/896 (0) G3 vs. G5b: G3: 0/615 (0) G5b: 0/896 (0) G4 vs. G5b: G4: 1/911 (0) G5b: 0/896 (0) |
Major hypoglycemic episodes G1: NR G2: 1.0% (6/619) G3: 1.4% (9/615) G4: 1.8% (16/911) G5a: NR G5b: 0.7% (6/896) G2 vs. G5b RR, 1.45 (0.47 to 4.47) G3 vs. G5b RR, 2.19 (0.78 to 6.11) G4 vs. G5b RR, 2.62 (1.03 to 6.67) | NR | NR |
|
Kumar, 2014208 India |
G1: 0 G2: 0 |
G1: 0 G2: 0 |
G1: 0/107 (0) G2: 0/106 (0) |
Treatment-related AEs: G1: 6/107 (5.6) G2: 8/106 (7.5) RR, 0.74 (0.27 to 2.07) Serious adverse events: G1: 0 G2: 0 |
Abbreviations: AE=adverse events; CI=confidence interval; DESMOND=Diabetes education and self management for ongoing and newly diagnosed programme; G=group; HR=hazard ratio; KQ=key question; NR=not reported; RR=relative risk; UKPDS=United Kingdom Prospective Diabetes Study; vs.=versus.
Appendix E Table 12Harms Reported in Included Trials of Interventions for People With Prediabetes (KQ 6)
|
Source First Author, year Trial Name | Groups (N participants) Followup, y |
Hypoglycemic Events G1 N (%) G2 N (%) |
All Cause Withdrawals Due to Adverse Events G1 N (%) G2 N (%) |
Gastrointestinal Adverse Events G1 N (%) G2 N (%) |
Other Adverse Events G1 N (%) G2 N (%) |
|---|---|---|---|---|---|
|
Ackermann, 2015139 Reaching Out to Prevent Increases in Diabetes (RAPID) |
G1: Group-based YMCA DPP intervention (n=257) G2: Usual care plus brief counseling & information on community resources (n=252) 1 year | NR | NR | NR |
Joint sprains or strains G1: 58 (22.6) G2: 58 (22.9) P = 0.99 Muscle or joint aches G1: 125 (48.6) G2: 127 (50.5) P = 0.7 |
|
Bhopal, 201436 Welsh, 2016220 The Prevention of Diabetes and Obesity in South Asians (PODOSA) study |
G1: Lifestyle intervention with family support and visits to dietician (n=85) G2: Standardized advice with family support (n=86) 3 years | NR | NR | NR |
Total events perceived by participants to be attributable to the intervention: G1: 3 (3.5) G2: 4 (4.7) Moderate events perceived by participants to be attributable to the intervention: G1: 2 (2.3) - arthritis in knee causing pain on walking (n=1), and worries about changing habits (n=2) G2: 0 (0) |
|
Diabetes Prevention Program Research Group, 200280 Diabetes Prevention Program Research Group, 2005119 Diabetes Prevention Program Research Group, 201297 Diabetes Prevention Program Research Group, 201579 DPP |
G1: Intensive lifestyle intervention (n=1079; 910 enrolled in DPPOS) G2: Standard lifestyle recommendations plus metformin 850 mg twice daily (n=1073; 924 enrolled in DPPOS) G3: Standard lifestyle recommendation plus placebo twice daily (n=1082; 932 enrolled in DPPOS) DPP: 2.8 y DPPOS: 15y | NR | NR |
DPP (2.8 years): GI symptoms (events/per 100 person-years) G1: 12.9 G2: 77.8 G3: 30.7 G1 vs. G3, p <0.0167 G2 vs. G3, p <0.0167 |
DPP (2.8 years): No deaths attributed to study intervention Musculoskeletal symptoms (events per 100 person-years) G1: 24.1 G2: 20.0 G3: 21.1 G1 vs. G3, p<0.0167 Hospitalization (% with one or more admissions) G1: 15.6 G2: 15.9 G3: 16.1 DPPOS (DPP + DPPOS, 15 years post-randomization): Risk for sprains or fractures needing medical attention G1: 4.3 events per 100 patient years G2: 4.1 events per 100 patient years G3: 3.7 events per 100 patient years No cases of lactic acidosis were reported in about 40000 patient-years of followup |
|
Diabetes Prevention Program Research Group, 2012237 Diabetes Prevention Program Research Group, 2009146 Diabetes Prevention Program Research Group, 201579 Apolzan, 2019238 DPPOS |
G1: Standard lifestyle recommendations plus 850 mg metformin twice daily for 3.2 y; then open label metformin for additional 7-8 y and offered original DPP lifestyle intervention (n=924) G2: Standard lifestyle recommendation plus placebo twice daily and offered original DPP lifestyle intervention (n=932) Double blind phase: 2 y Open label phase: 9 y |
Non serious hypoglycemia events G1: 7 G2: 8 Serious hypoglycemia events G1: 0 G2: 0 | NR |
% reporting GI symptoms in past year (average during DPP through year 4): G1: 28% G2:16% p = 0.01 Rates of GI symptom reports declined throughout DPPOS and were similar between groups by years 6-9, but remained significantly higher (p<0.10) in G1 vs. G2 over DPP +DPPOS (average per group over 9-years NR) % of participants reporting GI symptoms attributed to study medication over past 3 months (average during DPP through year 4): G1: 9.5% G2: 1.1% p < 0.001 |
Adverse events during DPP (in metformin vs. placebo groups only): Non-serious anemia G1: 50 G2: 38 Serious anemia G1: 2 G2: 1 Lactic acidosis G1: 0 G2: 0 |
| Juul, 2016145 |
G1: Brief theory-based health promotion intervention (n=63) G2: Control (n=64) 1 year | NR | NR | NR | No adverse events were reported |
|
O’Brien, 2017142 The Promotora Effectiveness Versus Metformin Trial (PREVENT-DM) |
G1: Intensive group-based adaptation of the DPP lifestyle intervention delivered by promotoras (community healthcare workers (n=33) G2: Metformin 850 mg twice daily (n=29) G3: Standard care plus written educational materials on diabetes prevention (n=30) 1 year | NR |
Withdrawals due to medication side effects G1: 0 (0) G2: 1 (3.4) G3: 0 (0) |
GI adverse events: G1: 0 (0) G2: 8 (28) G3: 0 (0) |
Any adverse events: G1: 0 (0) G2: 10 (34.4) G3: 0 (0) Adverse events experienced in G2: Gastrointestinal: 8 (27.6) Dizziness/vertigo: 1 (3.4) Headache: 1 (3.4) |
|
Pan, 1997225 Li, 2008226 Li, 2014227 Gong, 2019228 China Da Qing Diabetes Prevention Outcomes Study (CDQDPOS) |
G1: Combined 6-year lifestyle (diet, exercise, or diet + exercise) intervention (n=438) G2: Control (n=138) 6 years (intervention); 23 years post-intervention followup; 30 years post-intervention followup | NR | NR | NR | No adverse events were recorded. |
|
Saito, 201187 ZPLS |
G1: Frequent intervention (received individual instructions and followup support for lifestyle modification 9 times over 36 months) (n=311) G2: Control group (received individual instructions and followup support for lifestyle modification 4 times over 12 months). (n=330) 3 years | NR | NR | NR | Authors report that there were no serious adverse events reported from any study center |
|
Sakane, 2015140 The Japan Diabetes Outcome Intervention Trial-1 (J-DOIT1) |
G1: 1-year telephone-delivered lifestyle support intervention (n=1,240) G2: Control (n=1,367) 4.2 years | NR | NR | NR |
All adverse events: G1: 24 (1.9) G2: 25 (1.8) Cancer: G1: 5 (0.4) G2: 8 (0.6) Musculoskeletal problems: G1: 6 G2: 3 Four cases of musculoskeletal problems in the intervention arm and one in the control arm might have been related to study treatment, per authors Other adverse events: G1: 9 (0.7) G2: 9 (0.7) |
|
Chiasson, 2002235 Chiasson, 2003236 STOP-NIDDM |
G1: Acarbose 100 mg 3x a day (n=714) G2: Placebo (n=715) 3.3 years | NR |
Medication discontinuation due to adverse events: G1: 136(19) G2: 37 (5) |
Any GI adverse events: G1: 597 (83) G2: 426 (60) p<0.001 Flatulence: G1: 486 (68) G2: 196 (27) Diarrhea: G1: 229 (32) G2: 123 (17) |
Patients with any adverse events: G1: 698 (98) G2: 675 (95) |
|
DeFronzo, 2011251 Espinoza, 2016252 Actos Now for Prevention of Diabetes Trial (ACT NOW) |
G1: Pioglitazone 30 mg/day for one month, increased to 45 mg/day (n=303) G2: Placebo (n=299) 2.4 years (median) | NR |
Withdrawals due to weight gain: G1: 9 G2: 3 |
Digestive system G1: 13 (4.29) G2: 12 (4.01) |
Patients experiencing any adverse event: G1: 141 (47) G2: 121 (40) p=0.03 Specific adverse events: Bone fractures G1: 8 (2.64) G2: 7 (2.34) Central nervous system G1: 6 (2.0) G2: 5 (1.67) Edema* G1: 39 (12.87) G2: 19 (6.27) p=0.007 Cancer: G1: 3 (1) G2: 8 (3) Endocrine system G1: 1 (0.33) G2: 3 (1.00) Immune system G1: 2 (0.66) G2: 4 (1.34) Musculoskeletal system G1: 12 (3.96) G2: 13 (4.35) Ophthalmologic system G1: 0 (0.00) G2: 1 (0.33) Respiratory system G1: 9 (2.97) G2: 6 (2.01) Reproductive system G1: 4 (1.32) G2: 4 (1.34) Skin G1: 6 (2.0) G2: 3 (1.00) Urogenital system G1: 5 (1.65) G2: 3 (1.00) Weight gain > 1 kg G1: 205 (67.66) G2: 128 (42.81) |
|
DREAM Trial Investigators, 2006253 DREAM Trial Investigators, 2006254 DREAM Trial Investigators, 2008255 Diabetes Reduction Assessment with ramipril and rosiglitazone Medication (DREAM) Trial |
G1: Ramipril 15 mg/day (n=2623) G2: Placebo (n=2646) G3: Rosiglitazone 0.8mg/day (n=2635) G4: Placebo (n=2634) Patients randomized twice, to ramipril or placebo and rosiglitazone or placebo due to 2×2 factorial design 3 years | NR |
Primary reasons for discontinuation of ramipril and placebo: Participant’s decision to stop medication G1: 456 (17.4) G2: 468 (17.7) Cough G1: 254 (9.7) G2: 48 (1.8) Physician’s advice G1: 60 (2.3) G2: 66 (2.5) Peripheral edema G1: 26 (1.0) G2: 29 (1.1) Angioedema G1: 3 (0.1) G2: 4 (0.2) Most common reasons for stopping rosiglitazone and placebo: Participant refusal G3: 503 (18.9) G4: 439 (16.7) Edema G3: 127 (4.8) G4: 41 (1.6) Physician’s advice G3: 50 (1.9) G4: 39 (1.5) Weight gain G3: 50 (1.9) G4: 15 (0.6) Hypoglycemia G3: 1 (0.04) G4: 3 (0.11) | NR | NR |
| Kaku, 2015218 |
G1: Sitagliptin 25g once daily (n=82) G2: Sitagliptin 50g once daily (n=77) G3: Placebo (n=83) 8 weeks |
Hypoglycemia requiring medical attention NR Any Hypoglycemia G1: 7 (8.6) G2: 5 (6.1) G3: 4 (5.1) Symptomatic hypoglycemia G1: 2 (2.5) G2: 0 (0.0) G3: 0 (0.0) | No participants withdrew due to adverse effects of study treatment |
GI disorders G1: 5 (6.2) G2: 4 (4.9) G3: 7 (9.0 |
No deaths occurred during the study Any drug-related adverse event G1: 10 (12.3) G2: 5 (6.1) G3: 7 (9.0) Other AEs classified by system organ classes with incidence ≥4 in one or more treatment groups: Infections and infestations G1: 8 (9.9) G2: 11 (13.4) G3: 12 (15.4) Metabolism and nutrition disorders G1: 7 (8.6) G2: 5 (6.1) G3: 4 (5.1) Respiratory, thoracic and mediastinal disorders G1: 3 (3.7) G2: 5 (6.1) G3: 1 (1.3) |
| Kawamori, 2009256 |
G1: Voglibose 0.2 mg TID 3x/daily (n=897) G2: Placebo (n=883) 48 weeks | NR |
Discontinuations due to any adverse events: G1: 62 (7%) G2: 55 (6%) p=0.57 Discontinuations due to adverse events attributable to intervention: G1: 46 (5%) G2: 24 (3%) p=0.01 | NR | NR |
|
le Roux, 2017115 SCALE Obesity and Prediabetes Trial |
G1: Liraglutide (starting at 0.6 mg daily; weekly 0.6 mg increases to 3.0 mg with standardized lifestyle counseling (n=1505) G2: Placebo with standardized lifestyle counseling (n=749) 3.3 years |
Severe hypoglycemic events requiring third-party assistance G1: 0 (0) G2: 0 (0) |
Withdrawals due to adverse events G1: 199 (13) G2: 46 (6) |
Nausea: G1: 614 (41) G2: 125 (17) Diarrhea: G1: 379 (41) G2: 107 (14) Pancreatitis G1:10 (0.6) G2: 2 (0.2) |
Total number of participants reporting any adverse events: G1: 1421 (95) G2: 668 (89) Total number of participants reporting any serious adverse events: G1: 227 (15) G2: 96 (13) Other specific adverse events: Malignant breast neoplasms in females G1: 7 (0.5) G2: 0 (0) Malignant thyroid neoplasms G1: 1 (0.1) G2: 0 (0) |
| Lu, 2011259 |
G1: Patients with I-IGT: acarbose (50 mg three times daily) + lifestyle intervention; patients with I-IFG or IFG/IGT: metformin (0.25 g 3x daily) + lifestyle intervention (n=106) G2: Annual diabetes education (n=104) 2 years | NR |
Withdrawal due to Adverse Event G1: 1 (0.9) G2: 0 (0) | NR | NR |
|
The NAVIGATOR Study Group, 2010260 The NAVIGATOR Study Group, 2010261 Currie, 2017262 Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) Trial |
G1: Nateglinide 60 mg/3 times daily (n=4645) G2: Placebo (n=4661) G3: Valsartan 160 mg/once daily (n=4631) G4: Placebo (n=4675) Patients randomized twice to nateglinide or placebo and valsartan or placebo due to 2×2 factorial design All patients also required to participate in lifestyle intervention program 5 years |
All hypo-glycemia adverse events G1: 911 (20) G2: 527 (11) G3: 731 (15.8) G4: 707 (15.1) Mild (maximum severity) G1: 676 G2: 411 Moderate (maximum severity) G1: 214 G2: 104 Severe (maximum severity) G1: 21 G2: 12 |
Discontinuation of the study drug due to an adverse event: G1: 520 (11.2) G2: 485 (10.4) G3: 556 (12.0) G4: 531 (11.4) |
Diarrhea G1: 593 (13) G2: 586 (13) G3: 612 (13.2) G4: 567 (12.1) |
Initiation of dialysis G3: 4 (0.1) G4: 4 (0.1) HR 0.97 (0.24 to 3.88) Serum creatinine >530 µmol/L G3: 1 (0) G4: 1 (0) HR 0.93 (0.06 to 4.9) Doubling of serum creatinine G3: 18 (0.4) G4: 18 (0.4) HR 1.00 (0.52 to 1.92) Hospitalization for renal failure G3: 34 (0.7) G4: 35 (0.7) HR 0.96 (0.6 to 1.54) Renal dysfunction adverse event G3: 118 (2.5) G4: 126 (2.7) HR 0.93 (0.73 to 1.20) Hypotension related G1: 1855 (40) G2: 1789 (38) G3: 1964 (42.4) G4: 1680 (35.9) p<0.001 for G3 vs. G4 Back pain G1: 752 (16) G2: 705 (15) G3: 775 (16.7) G4: 682 (14.6) Nasopharyingitis G1: 807 (17) G2: 798 (17) G3: 808 (17.4) G4: 797 (17.0) Arthralgia G1: 759 (16) G2: 762 (16) G3: 758 (16.4) G4: 763 (16.3) Hypertension G1: 797 (17) G2: 846 (18) G3: 693 (15.0) G4: 950 (20.3) Renal dysfunction G3: 136 (2.9) G4: 146 (3.1) Hyperkalemia G3: 35 (0.8) G4: 35 (0.7) Hypokalemia G3: 45 (1.0) G4: 83 (1.8) Angioedema G3: 89 (1.9) G4: 123 (2.6) Influenza G1: 602 (13) G2: 630 (14) G3: 615 (13.3) G4: 617 (13.2) Pain in extremity G1: 568 (12) G2: 530 (11) G3: 567 (12.2) G4: 531 (11.4) Osteoarthritis G1: 576 (12) G2: 578 (12) G3: 554 (12.0) G4: 600 (12.8) Upper respiratory tract infection G1: 525 (11) G2: 556 (12) G3: 546 (11.8) G4: 535 (11.4) Headache G1: 559 (12) G2: 604 (13) G3: 537 (11.6) G4: 626 (13.4) Cough G1: 478 (10) G2: 450 (10) G3: 462 (10.0) G4: 466 (10.0) Fatigue G1: 462 (10) G2: 432 (9) Peripheral edema G1: 500 (11) G2: 486 (10) G3: 431 (9.3) G4: 555 (11.9) Bronchitis G1: 477 (10) G2: 477 (10) G3: 463 (10.0) G4: 491 (10.5) |
|
Nijpels, 2008263 DAISI |
G1: Acarbose 50 mg 3x daily (n=60) G2: Placebo (n=58) 3 years | NR |
Withdrawals due to adverse events: G1: 22 (36.7) G2: 8 (13.8) | NR | NR |
|
Ramachandran, 2009265 IDPP-2 |
G1: Pioglitazone, 30 mg daily plus lifestyle modification (n=204) G2: Placebo plus lifestyle modification (n=203) 3 years | NR | NR | NR |
Other major events (not defined), excluding death or CVD: G1: 4 G2: 10 Minor adverse events (hypoglycemic symptoms, joint pain, fracture, fever, renal stone, hypothyroidism, breathlessness, elevated liver enzymes): G1: 28 G2: 22 |
| Pan, 2003246 |
G1: Acarbose 50 mg 3x daily (n=125) G2: Placebo (n=127) 16 weeks | NR |
Withdrawn due to adverse events G1: 2 (1.6) G2: 3 (2.4) |
Flatulence G1: NR (15.9) G2: NR (6.1) Enlarged abdomen G2: NR (13.5) G1: NR (3.8) Diarrhea G2: NR (9.5) G1: NR (2.3) Hepatitis: G1: 1 (0.8) G2: 0 (0.0) |
Drug-related adverse events with a ‘possible’ or ‘probable’ relation to the study drug G1: NR (35.7) G2: NR (18.2) Tenosynovitis G1: 0 (0.0) G2 1 (0.8) Glaucoma: G1: 1 (0.8) G2: 0 (0.0) Cerebral infarction G1: 1 (0.8) G2: 0 (0.0) |
|
Weber, 2016222 Gokulakrishnan, 2017223 Diabetes Community Lifestyle Improvement Program (D-CLIP) |
G1: Stepwise intervention of adapted DPP lifestyle classes plus metformin 500 mg twice daily at 4 months if at high risk of developing diabetes (n=283) G2: Standard of care (n=295) 3 years | NR | NR | NR |
No severe adverse events (e.g., hospitalization, severe injury or illness) related to participation in the study, no injuries related to the exercise program, and no adverse events from diet changes Some participants reported mild or moderate gastritis related to taking metformin, but none of these cases were severe enough to stop taking the medication One participant developed a rash after taking metformin, which resolved after metformin was discontinued. |
|
Zinman, 2010267 CAnadian Normoglycemia Outcomes Evaluation trial (CANOE) |
G1: rosiglitazone 2 mg and metformin 500 twice daily and lifestyle intervention (n=103) G2: placebo and lifestyle intervention (n=104) 3.9 years |
Hypoglycemia (severity NR): G1: 2 (2) G2: 1 (1) |
Stopped study medication due to concerns about side-effects from rosiglitazone: G1: 4 (4) G2: 7 (7) |
Any GI event (diarrhea, nausea/vomiting, abdominal pain, constipation, flatulence, frequent/soft stools): G1: 37 G2: 19 Diarrhea G1: 16 (16) G2: 6 (6) p=0.025 |
Any adverse effect potentially related to study or study drug (diarrhea, nausea/vomiting, abdominal pain, constipation, flatulence, frequent/soft stools, swollen ankles, bloating/water retention, allergic reaction, vertigo) G1: 42 (41) G2: 27 (26) |
- *
Edema was defined as an increase above baseline by two or more grades on one or more distinct study visits.
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