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A placebo‐controlled trial of exenatide twice‐daily added to thiazolidinediones alone or in combination with metformin
Author(s) -
Liutkus J.,
Rosas Guzman J.,
Norwood P.,
Pop L.,
Northrup J.,
Cao D.,
Trautmann M.
Publication year - 2010
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/j.1463-1326.2010.01251.x
Subject(s) - exenatide , placebo , metformin , medicine , clinical endpoint , type 2 diabetes , nausea , adverse effect , gastroenterology , diabetes mellitus , randomized controlled trial , endocrinology , insulin , alternative medicine , pathology
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 [HbA 1c 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 HbA 1c change at endpoint (Week 26 or last‐observation‐carried‐forward). Results: Only 8 subjects were treated with concomitant TZD alone. Exenatide reduced HbA 1c 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 HbA 1c 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 <3.0 mmol/l) minor hypoglycaemia was experienced by 4 and 2% of subjects treated with exenatide and placebo, respectively. Incidence of hypoglycaemia was not significantly different between groups. Conclusions: Exenatide added to TZDs alone or in combination with metformin significantly improved glycaemic control as determined by significant improvement in HbA 1c without associated hypoglycaemia.