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Aims  Glucagon‐like peptide‐1 ( GLP ‐1) receptor agonists improve blood glucose control by enhancing glucose‐sensitive insulin release, delaying gastric emptying and reducing postprandial glucagon secretion. The studies reported here investigated the insulin response to an intravenous (iv) glucose challenge after injection of lixisenatide (LIXI) 20 µg or placebo.    Methods  Two single‐centre, double‐blind, randomized, placebo‐controlled, single‐dose, crossover studies were performed in healthy subjects ( HS ) and people with type 2 diabetes mellitus ( T2DM ). Participants received subcutaneous LIXI or placebo 2 h before an iv glucose challenge. Study endpoints included first‐ and second‐phase insulin response, insulin concentration (INS), glucagon response and glucose disposal rate ( K  glucose ). LIXI exposure was measured over 12 h.    Results  LIXI 20 µg reached maximum concentration after 2 h and resensitized first‐phase insulin secretion by 2.8‐fold in  T2DM  to rates comparable with those in  HS  on placebo, and raised second‐phase insulin secretion by 1.6‐fold in  T2DM . INS rose correspondingly and glucose disposal was accelerated by 1.8‐fold in  T2DM . First‐phase insulin secretion and glucose disposal were also augmented by LIXI in  HS , whereas second‐phase insulin secretion reduced blood glucose concentrations to below fasting levels and then ceased, accompanied by a rapid, short‐lasting rise in glucagon. Otherwise, suppression of glucagon release subsequent to augmentation of insulin release was unaffected in  T2DM  and in  HS .    Conclusions  LIXI resensitized the insulin response to an iv glucose challenge in people with  T2DM , thereby accelerating glucose disposal to nearly physiological intensity, and did not impair counter‐regulation to low glucose levels by glucagon.

diabetes, obesity and metabolism

Lixisenatide resensitizes the insulin‐secretory response to intravenous glucose challenge in people with type 2 diabetes – a study in both people with type 2 diabetes and healthy subjects