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Lixisenatide may reduce glucagon, epinephrine in type 2 diabetes without impairing hypoglycemia response
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Patients with type 2 diabetes treated with lixisenatide as add-on to insulin experienced reduced glucagon and epinephrine levels while maintaining hypoglycemia counter-regulation, according to study findings published in Diabetes Care.
“Lixisenatide is a newly developed [glucagon-like peptide-1] receptor agonist that is based on the structure of exendin-4,” the researchers wrote. “It improves glycemia with low risk for hypoglycemia in monotherapy, in association with metformin, and in combination with insulin.”
Bo Ahrén, MD, PhD, and colleagues from the department of clinical sciences at Lund University in Sweden evaluated 18 adults (mean age, 55 years) with type 2 diabetes treated with basal insulin and metformin. In this crossover study, participants were assigned to lixisenatide (Sanofi) or placebo for 6 weeks in random order with a 4-week washout period in between. After the 6 weeks of treatment, all participants underwent a two-step hyperinsulinemic clamp at 3.5 mmol/L and 2.8 mmol/L. Researchers sought to determine the effect of lixisenatide on the hormonal counter-regulatory responses in insulin-induced hypoglycemia as an add-on to basal insulin therapy.
HbA1c was reduced more with lixisenatide compared with placebo during the 6-week treatment (P < .001). Similarly, fasting blood glucose (P = .046), body weight (P = .043) and daily insulin dose (P = .023) were reduced with lixisenatide compared with placebo.
At the 3.5 mmol/L hypoglycemic level, glucagon was lower during lixisenatide treatment compared with placebo (P = .005). Glucagon levels did not differ between the two groups at the 2.8 mmol/L hypoglycemic level. Epinephrine levels were significantly lower during lixisenatide treatment compared with placebo at the hypoglycemic level of 3.5 mmol/L.
“In summary, we conclude that in insulin-treated patients with type 2 diabetes at a glucose level of 3.5 mmol/L, lixisenatide reduces glucagon and epinephrine levels compared with placebo, whereas the glucagon and epinephrine counter-regulation to deep hypoglycemia at 2.8 mmol/L is sustained,” the researchers wrote. – by Amber Cox
Disclosure: Ahrén reports consulting for and/or receiving lecture fees from AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, GlaxoSmithKline, Merck, Novartis, Novo Nordisk, Sanofi and Takeda.
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