A placebo-controlled trial of exenatide twice-daily added to thiazolidinediones alone or in combination with metformin.
OBJECTIVE
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.
Medicine Professional Corporation, Cambridge, Ontario, Canada. jfliutkus@rogers.com
J
J
Liutkus
J
J
Rosas Guzman
P
P
Norwood
L
L
Pop
J
J
Northrup
D
D
Cao
M
M
Trautmann
D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D004311:Double-Blind Method; D000077270:Exenatide; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects*; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000009:adverse effects; D008875:Middle Aged; D009325:Nausea / Q000139:chemically induced; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D010919:Placebos / Q000008:administration & dosage*; D045162:Thiazolidinediones / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014688:Venoms / Q000008:administration & dosage* / Q000009:adverse effects; D014839:Vomiting / Q000139:chemically induced
D000077270:Exenatide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D008687:Metformin; D010455:Peptides; D010919:Placebos; D045162:Thiazolidinediones; D014688:Venoms