Glucose-Lowering Medications and Angina Burden in Patients with Stable Coronary Disease: results from the Type 2 Diabetes Evaluation of Ranolazine in Subjects With Chronic Stable Angina (TERISA) Trial

Background: Different classes of glucose-lowering medications have been associated with varying risks of myocardial infarction and cardiovascular death, but their effect on angina is unknown. Therefore, we sought to determine the association of different glucose-lowering medication classes with angina frequency and nitroglycerin (NTG) use.

Methods: We performed a secondary, observational analysis of the TERISA multinational trial, which evaluated the antianginal effect of ranolazine versus placebo in patients with type 2 diabetes mellitus, documented coronary disease, and a 3-month history of stable angina. Patients recorded angina and NTG use in a daily dairy for 3 weeks prior to randomization, to establish their baseline angina burden for the trial. We then examined the association of different glucose-lowering medication classes with baseline angina and NTG use using multivariable linear regression.

Results: Among 952 patients enrolled, 494 were taking metformin, 504 taking a sulfonylurea, 186 taking insulin, 29 taking DPP-4 inhibitors, 22 taking other glucose-lowering medications, and 68 were diet-controlled only. After adjustment for demographic and clinical factors, patients taking versus not taking sulfonylureas had 1.02 more episodes of angina and used 0.93 more doses of NTG per week (P = .002 and .011, respectively). The weekly angina burden or NTG use was not different for those taking versus not taking metformin (P > .7 for both). Patients taking versus not taking insulin had 0.83 more episodes of angina and used 1.40 more NTG doses per week, increases evident only in those taking insulin without concomitant metformin (Pinteraction < .05 for both).

Conclusion: Different classes of glucose-lowering medications were associated with varying angina burden in patients with type 2 diabetes mellitus and stable coronary disease. Patients taking sulfonylureas or insulin had more angina and used more NTG, while metformin was not associated with angina burden. Given the increasing prevalence of glucose abnormalities in patients with coronary disease, a better understanding of the relationship between glucose-lowering medications and angina is needed.