In the Journals

Inhaled formoterol may lessen hypoglycemia in adults with type 1 diabetes

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July 10, 2015

Inhalation of the long-acting selective beta 2-adrenergic receptor agonist formoterol can prevent or treat hypoglycemia in adults with type 1 diabetes, according to research in Diabetes Care.

In a study designed to stimulate episodes of insulin-induced hypoglycemia in adults with and without type 1 diabetes, researchers found that inhaled formoterol prevented an acute hypoglycemic episode.

“These findings suggest that inhaled formoterol may have potential value as a preventive therapy for iatrogenic hypoglycemia, particularly in patients with type 1 diabetes with hypoglycemia-associated autonomic failure and frequent episodes of nocturnal hypoglycemia,” the researchers wrote.

Renata D. Belfort De Aguiar, MD, PhD, an endocrinology professor at Yale University School of Medicine, and colleagues analyzed data from seven participants with type 1 diabetes (five women; mean age, 31 years) matched by age, sex and BMI with seven healthy controls without diabetes (four women; mean age, 36 years) randomly assigned to inhaled formoterol or a placebo. Within the diabetes arm, six participants reported using an insulin pump; one reported taking multiple daily insulin injections.

Renata D. Belfort De Aguiar

Renata D. Belfort De Aguiar

After a 10-hour overnight fast, participants attended two separate morning visits to receive 48 µg of inhaled formoterol or an inhaled placebo, followed by a hyperinsulinemic euglycemic-hypoglycemic clamp. Researchers initiated an IV infusion of insulin; a 20% dextrose infusion was also initiated and adjusted based on plasma glucose levels to maintain in the euglycemic range for 30 minutes. After 30 minutes, researchers allowed plasma glucose levels to drop freely for 60 minutes, with vital signs measured every 30 minutes and researchers recording symptoms self-reported by participants.

In a second protocol in the same study, five participants with type 1 diabetes were assigned inhaled formoterol to assess its effect as a preventive therapy for insulin-induced hypoglycemia. Those participants received inhaled formoterol 60 minutes before being exposed to a twofold increase in the basal insulin infusion rate, maintained for 60 minutes until the end of the study. Researchers monitored glucose levels every 5 to 10 minutes and allowed levels to drop freely. Researchers initiated an IV infusion of 20% dextrose if plasma glucose fell to a moderately severe hypoglycemic range.

Researchers found that inhaled formoterol decreased the glucose infusion rate needed to maintain plasma glucose at target levels by 45% to 50% (P < .05). Formoterol had no significant effect on glucagon, epinephrine, cortisol or growth hormone release.

Participants in the second protocol’s placebo group saw glucose levels drop to 58 mg/dL, whereas inhaled formoterol prevented hypoglycemia in the treatment group (P < .001).

“These results imply that the metabolic effects of inhaled formoterol are most likely due to a direct effect of formoterol on beta-2 receptors in the peripheral tissues,” the researchers wrote. “However, it is possible that formoterol may affect peripheral metabolism indirectly by activating beta-2 receptors in the hypothalamus.”

More studies will be needed to define the optimal formoterol dose and time for it to be delivered, the researchers wrote, as well as its long-term effects on glycemic control in patients with type 1 diabetes. by Regina Schaffer

Disclosure: One researcher reports serving on a Merck & Co. data safety monitoring board for a type 2 diabetes medication that is unrelated to formoterol. The other researchers report no relevant financial disclosures.

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