Glucagon dynamics during hypoglycaemia and food‐re‐challenge following treatment with vildagliptin in insulin‐treated patients with type 2 diabetes. Issue 9 (17th March 2014)

• Record Type: Journal Article
• Authors: Farngren, J.; Persson, M.; Schweizer, A.; Foley, J. E.; Ahrén, B.
• Is Part Of: Diabetes, obesity & metabolism. Volume 16:Issue 9(2014:Sep.)
• Page Start: 812
• Page End: 818
• Publication Date: 2014-03-17
• Subjects: Diabetes -- Periodicals; Obesity -- Periodicals; Metabolism -- Disorders -- Periodicals; Clinical pharmacology -- Periodicals; 616.462
• DOI: 10.1111/dom.12284
• Languages: English
• ISSNs: 1462-8902

Abstract

<abstract abstract-type="main" id="dom12284-abs-0001"> <title>Abstract</title> <sec id="dom12284-sec-0001" sec-type="section"> <title>Aims</title> <p id="dom12284-para-0001">To determine the effects of dipeptidyl peptidase‐4 (DPP‐4) inhibition on glucagon dynamics in patients with insulin‐treated type 2 diabetes (T2D).</p> </sec> <sec id="dom12284-sec-0002" sec-type="section"> <title>Methods</title> <p id="dom12284-para-0002">The study was a single‐centre, double‐blind, randomized, placebo controlled crossover study in patients with T2D, mean age 59 ± 6 (s.d.) years and mean haemoglobin A1c 7.7 ± 0.8%, treated with exogenous insulin with or without oral antihyperglycaemic agents. Patients received vildagliptin (50 mg BID) or placebo as add‐on to insulin for 4 weeks in random order with a 4‐week washout in‐between. On day 28 of the respective treatment, patients were served a standard meal (500 kcal) followed by a hyperinsulinaemic hypoglycaemic clamp (target 2.5 mmol/l) and a subsequent food re‐challenge (700 kcal). The completers population (n = 29) was analysed.</p> </sec> <sec id="dom12284-sec-0003" sec-type="section"> <title>Results</title> <p id="dom12284-para-0003">Glucose levels were lower with vildagliptin than with placebo during the meal [areas under the curve (AUC) 1.23 ± 0.07 vs. 1.46 ± 0.05 mol/l min, P < 0.001] and similar between the groups during the clamp. During the meal, glucagon levels were lower with vildagliptin (AUC 1.98 ± 0.15 vs. 2.15 ± 0.17 nmol/l min, P = 0.016). In contrast, the glucagon counter‐regulation to the insulin‐induced hypoglycaemia was sustained by vildagliptin (6.05 ± 1.20 pmol/l during vildagliptin vs.6.94 ± 1.09 pmol/l during placebo, NS). During the food re‐challenge after hypoglycaemia, glucagon levels were, again, significantly lower after vildagliptin (AUC 1.30 ± 0.11 vs. 1.52 ± 0.12 nmol/l min, P < 0.039). Glucagon‐like peptide‐1 (GLP‐1) and glucose‐dependent insulinotropic polypeptide (GIP) levels were significantly elevated by vildagliptin compared to placebo during meal, hypoglycaemia and food re‐challenge.</p> </sec> <sec id="dom12284-sec-0004" sec-type="section"> <title>Conclusions</title> <p id="dom12284-para-0004">Vildagliptin action to block GLP‐1 and GIP inactivation by DPP‐4 improves glucagon dynamics during hypoglycaemia, hyperglycaemia and food re‐challenge.</p> </sec> </abstract>