The effect of adding exenatide to a thiazolidinedione in suboptimally controlled type 2 diabetes: a randomized trial.

Abstract

BACKGROUND:

Exenatide therapy is effective in combination with metformin or sulfonylureas for treating type 2 diabetes. Thiazolidinediones (TZDs) also are commonly used, but the efficacy of exenatide with a TZD has not been reported.

OBJECTIVE:

To compare the effects of exenatide versus placebo on glycemic control.

DESIGN:

Placebo run-in, randomized, double-blind, placebo-controlled trial conducted from May 2004 to August 2005.

SETTING:

49 sites in Canada, Spain, and the United States.

PATIENTS:

233 (exenatide group, n = 121; placebo group, n = 112) patients with type 2 diabetes that was suboptimally controlled with TZD treatment (with or without metformin). Mean (+/-SE) baseline glycated hemoglobin A1c level was 7.9% +/- 0.1%.

INTERVENTIONS:

Subcutaneous abdominal injections of 10 microg of exenatide or placebo twice daily, added to a TZD (with or without metformin) for 16 weeks.

MEASUREMENTS:

The primary outcome was change from baseline in hemoglobin A1c level. Other outcomes were fasting serum glucose level, body weight, self-monitored blood glucose level, and any adverse events.

RESULTS:

Exenatide treatment reduced hemoglobin A(1c) level (mean difference, -0.98% [95% CI, -1.21% to -0.74%]), serum fasting glucose level (mean difference, -1.69 mmol/L [-30.5 mg/dL] [CI, -2.22 to -1.17 mmol/L {-40.0 to -21.1 mg/dL}]), and body weight (mean difference, -1.51 kg [CI, -2.15 to -0.88 kg]). Sixteen percent of patients in the exenatide group and 2% of patients in the placebo group discontinued treatment because of adverse events. In the exenatide group, 40% (n = 48) of patients experienced nausea (mostly mild [n = 21] or moderate [n = 19]), 13% experienced vomiting, and 11% experienced hypoglycemia. In the placebo group, 15% of patients experienced nausea, 1% experienced vomiting, and 7% experienced hypoglycemia.

LIMITATIONS:

Combinations with TZDs and sulfonylureas were not tested. Trial duration was relatively short. Only 71% and 86% of patients in the exenatide and placebo groups, respectively, completed the study.

CONCLUSIONS:

Exenatide therapy improved glycemic control, reduced body weight, and caused gastrointestinal symptoms more than placebo in patients with type 2 diabetes that was suboptimally controlled with TZD therapy. ClinicalTrials.gov registration number: NCT00099320. For more information on exenatide click here.

• Authors: Bernard Zinman, Byron J Hoogwerf, Santiago Durán García, Denái R Milton, Joseph M Giaconia, Dennis D Kim, Michael E Trautmann, Robert G Brodows
• Journal: Annals of internal medicine (Ann Intern Med) Vol. 146 Issue 7 Pg. 477-85 (Apr 03 2007) ISSN: 1539-3704 [Electronic] United States
• PMID: 17404349 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Blood Glucose
• Glycated Hemoglobin A
• Hypoglycemic Agents
• Peptides
• Thiazolidinediones
• Venoms
• Metformin
• Exenatide
• 2,4-thiazolidinedione

Topics

• Adult
• Aged
• Blood Glucose (metabolism)
• Blood Glucose Self-Monitoring
• Diabetes Mellitus, Type 2 (blood, drug therapy, physiopathology)
• Double-Blind Method
• Drug Therapy, Combination
• Exenatide
• Female
• Glycated Hemoglobin (metabolism)
• Humans
• Hypoglycemia (chemically induced)
• Hypoglycemic Agents (adverse effects, therapeutic use)
• Injections, Subcutaneous
• Insulin-Secreting Cells (physiology)
• Male
• Metformin (therapeutic use)
• Middle Aged
• Nausea (chemically induced)
• Peptides (adverse effects, therapeutic use)
• Thiazolidinediones (therapeutic use)
• Venoms (adverse effects, therapeutic use)
• Vomiting (chemically induced)
• Weight Loss (drug effects)