Inhaled Formoterol Diminishes Insulin-Induced Hypoglycemia in Type 1 Diabetes

Diabetes Care. 2015 Sep;38(9):1736-41. doi: 10.2337/dc14-2472. Epub 2015 Jul 7.

Abstract

Objective: Hypoglycemia is one of the major factors limiting implementation of tight glycemic control in patients with type 1 diabetes and is associated with increased morbidity and mortality during intensive insulin treatment. β-2 Adrenergic receptor (AR) agonists have been reported to diminish nocturnal hypoglycemia; however, whether long-acting inhaled β-2 AR agonists could potentially be used to treat or prevent hypoglycemia has not been established.

Research design and methods: Seven patients with type 1 diabetes and seven healthy control subjects received inhaled formoterol (48 μg), a highly specific β-2 AR agonist, or a placebo during a hyperinsulinemic-hypoglycemic clamp study to evaluate its capacity to antagonize the effect of insulin. In a second set of studies, five subjects with type 1 diabetes received inhaled formoterol to assess its effect as a preventive therapy for insulin-induced hypoglycemia.

Results: During a hyperinsulinemic-hypoglycemic clamp, compared with placebo, inhaled formoterol decreased the glucose infusion rate required to maintain plasma glucose at a target level by 45-50% (P < 0.05). There was no significant effect on glucagon, epinephrine, cortisol, or growth hormone release (P = NS). Furthermore, in volunteers with type 1 diabetes 1 h after increasing basal insulin delivery twofold, glucose levels dropped to 58 ± 5 mg/dL, whereas hypoglycemia was prevented by inhaled formoterol (P < 0.001).

Conclusions: Inhalation of the β-2 AR-specific agonist formoterol may be useful in the prevention or treatment of acute hypoglycemia and thus may help patients with type 1 diabetes achieve optimal glucose control more safely.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adult
  • Aged
  • Blood Glucose / analysis
  • Diabetes Mellitus, Type 1 / drug therapy*
  • Female
  • Formoterol Fumarate / administration & dosage*
  • Glucose Clamp Technique
  • Growth Hormone / blood
  • Humans
  • Hypoglycemia / chemically induced
  • Hypoglycemia / drug therapy*
  • Hypoglycemic Agents / adverse effects
  • Insulin / adverse effects
  • Male
  • Middle Aged

Substances

  • Adrenergic beta-2 Receptor Agonists
  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin
  • Growth Hormone
  • Formoterol Fumarate