| 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
(Affiliation: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, and University of Toronto, Toronto, Ontario, Canada. zinman at mshri.on.ca)
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| Journal | Annals of internal medicine
(Ann Intern Med)
Vol. 146
Issue 7
Pg. 477-85
(Apr 3 2007)
ISSN: 1539-3704 United States |
| PMID | 17404349
(Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
| Chemical References |
- Blood Glucose
- Hemoglobin A, Glycosylated
- Hypoglycemic Agents
- Peptides
- Thiazolidinediones
- Venoms
- exenatide
- 2,4-thiazolidinedione
- Metformin
|
| Topics |
- Adult
- Aged
- Blood Glucose
(metabolism)
- Blood Glucose Self-Monitoring
- Diabetes Mellitus, Type 2
(blood, drug therapy, physiopathology)
- Double-Blind Method
- Drug Therapy, Combination
- Female
- Hemoglobin A, Glycosylated
(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)
|
