placebo‐controlled trial of exenatide twice‐daily added to thiazolidinediones alone or in combination with metformin

• Published in: Diabetes, obesity & metabolism obesity & metabolism, 2010-12, Vol.12 (12), p.1058-1065
• Main Authors: Liutkus, J, Rosas Guzman, J, Norwood, P, Pop, L, Northrup, J, Cao, D, Trautmann, M
• Format: Article
• Language: English
• Subjects: Antidiabetics; Body weight; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - complications; Diabetes Mellitus, Type 2 - drug therapy; Double-Blind Method; exenatide; Female; glycaemic control; Glycated Hemoglobin A - analysis; Glycated Hemoglobin A - drug effects; Humans; Hypoglycemia; Hypoglycemic Agents - administration & dosage; Male; Metformin; Metformin - administration & dosage; Metformin - adverse effects; Middle Aged; Nausea - chemically induced; Peptides - administration & dosage; Peptides - adverse effects; Placebos; Placebos - administration & dosage; Thiazolidinediones; Thiazolidinediones - administration & dosage; Thiazolidinediones - adverse effects; Treatment Outcome; type 2 diabetes; Venoms - administration & dosage; Venoms - adverse effects; Vomiting - chemically induced
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/j.1463-1326.2010.01251.x

Aim: To test the hypothesis that glycaemic control with exenatide added to thiazolidinediones (TZDs) with or without metformin was superior to placebo. Methods: A 26‐week, multi‐country (Canada, Mexico, Romania, South Africa and the USA), randomized, double‐blind, placebo‐controlled study compared exenatide twice‐daily vs. placebo in 165 subjects suboptimally controlled with TZDs with or without metformin [HbA₁c 8.2% (s.d. 0.9), fasting serum glucose 9.1 (2.6) mmol/l, body weight 93.9 (17.8) kg, diabetes duration 6.4 (4.3) years]. After a 2‐week, single‐blind, lead‐in period, subjects were randomly assigned (2 : 1) to add exenatide or placebo to current regimens. The primary endpoint was HbA₁c change at endpoint (Week 26 or last‐observation‐carried‐forward). Results: Only 8 subjects were treated with concomitant TZD alone. Exenatide reduced HbA₁c significantly more than placebo [−0.84% (s.e. 0.20) vs. −0.10% (0.23), treatment difference −0.74% (0.16), p < 0.001)]. Mean reductions in body weight were similar in both treatments at endpoint [exenatide, −1.4 (s.e. 0.6) kg vs. placebo, −0.8 (0.7) kg, p = 0.176)]. Nearly 71% of subjects had both a reduction in HbA₁c and body weight with exenatide compared with 54% with placebo. The most common adverse events (exenatide vs. placebo) were nausea (12% vs. 2%, p = 0.037), vomiting (8% vs. 0%, p = 0.031) and headache (4% vs. 4%). Confirmed (blood glucose