Robert J. Heine, MD, PhD; Luc F. Van Gaal, MD; Don Johns, PhD; Michael J. Mihm, PhD; Mario H. Widel, MS; Robert G. Brodows, MD; for the GWAA Study Group*
ClinicalTrials.gov Identifier: NCT00082381
Acknowledgments: The authors thank the statistical consultants, James Symanowski and Craig Mallinckrodt, for their contributions. They also thank Patricia Johnson, Deborah Wimberley, Ingrid Hensley, and Jude Burger for their contributions to the conduct of the study and development of the manuscript.
Grant Support: By Eli Lilly and Company, Inc., and Amylin Pharmaceuticals, Inc.
Potential Financial Conflicts of Interest: Employment: D. Johns (Eli Lilly and Company, Inc.), M.J. Mihm (Eli Lilly and Company, Inc.), M.H. Widel (Eli Lilly and Company, Inc.), R.G. Brodows (Eli Lilly and Company, Inc.); Consultancies: R.J. Heine (Amylin Pharmaceuticals, Inc.); Stock ownership or options (other than mutual funds): D. Johns (Eli Lilly and Company, Inc.), M.J. Mihm (Eli Lilly and Company, Inc.), M.H. Widel (Eli Lilly and Company, Inc.), R.G. Brodows (Eli Lilly and Company, Inc.); Grants received: R.J. Heine (Amylin Pharmaceuticals, Inc.).
Requests for Single Reprints: Robert J. Heine, MD, PhD, Diabetes Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
Current Author Addresses: Dr. Heine: Diabetes Center, VU University Medical Center, PO Box 7057, 1007 MB Amsterdam, the Netherlands.
Dr. Van Gaal: University Hospital of Antwerp, Wilrijkstraat 10, B-2650 Edegem, Antwerp, Belgium.
Drs. Johns and Mihm, Mr. Widel, and Dr. Brodows: Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, IN 46285.
Author Contributions: Conception and design: R.J. Heine, D. Johns, R.G. Brodows. Analysis and interpretation of the data: R.J. Heine, L.F. Van Gaal, D. Johns, M.J. Mihm, R.G. Brodows. Drafting of the article: R.J. Heine, M.J. Mihm. Critical revision of the article for important intellectual content: R.J. Heine, L.F. Van Gaal, D. Johns, R.G. Brodows. Final approval of the article: R.J. Heine, L.F. Van Gaal, D. Johns, M.J. Mihm, R.G. Brodows. Provision of study materials or patients: L.F. Van Gaal, R.G. Brodows. Statistical expertise: D. Johns. Obtaining of funding: R.J. Heine.Collection and assembly of data: L.F. Van Gaal, D. Johns, R.G. Brodows.
Physicians may use either insulin or exenatide injections for patients with type 2 diabetes mellitus who have poor glycemic control despite taking oral blood glucose–lowering drugs.
To compare effects of exenatide and insulin glargine on glycemic control in patients with type 2 diabetes mellitus that is suboptimally controlled with metformin and a sulfonylurea.
26-week multicenter, open-label, randomized, controlled trial.
82 outpatient study centers in 13 countries.
551 patients with type 2 diabetes and inadequate glycemic control (defined as hemoglobin A1c level ranging from 7.0% to 10.0%) despite combination metformin and sulfonylurea therapy.
Exenatide, 10 µg twice daily, or insulin glargine, 1 daily dose titrated to maintain fasting blood glucose levels of less than 5.6 mmol/L (<100 mg/dL).
Hemoglobin A1c level, fasting plasma glucose level, body weight, 7-point self-monitored blood glucose, standardized test-meal challenge, safety, and tolerability.
Baseline mean hemoglobin A1c level was 8.2% for patients receiving exenatide and 8.3% for those receiving insulin glargine. At week 26, both exenatide and insulin glargine reduced hemoglobin A1c levels by 1.11% (difference, 0.017 percentage point [95% CI, −0.123 to 0.157 percentage point]). Exenatide reduced postprandial glucose excursions more than insulin glargine, while insulin glargine reduced fasting glucose concentrations more than exenatide. Body weight decreased 2.3 kg with exenatide and increased 1.8 kg with insulin glargine (difference, −4.1 kg [CI, −4.6 to −3.5 kg]). Rates of symptomatic hypoglycemia were similar, but nocturnal hypoglycemia occurred less frequently with exenatide (0.9 event/patient-year versus 2.4 events/patient-year; difference, −1.6 events/patient-year [CI, −2.3 to −0.9 event/patient year]). Gastrointestinal symptoms were more common in the exenatide group than in the insulin glargine group, including nausea (57.1% vs. 8.6%), vomiting (17.4% vs. 3.7%) and diarrhea (8.5% vs. 3.0%).
The trial was open-label and did not assess clinical complications related to diabetes. Of the 551 participants, 19.4% of those receiving exenatide and 9.7% of those receiving insulin glargine withdrew from the study. Only 21.6% of the insulin glargine group and 8.6% of the exenatide group achieved the target level for fasting plasma glucose of less than 5.6 mmol/L (<100 mg/dL).
Exenatide and insulin glargine achieved similar improvements in overall glycemic control in patients with type 2 diabetes that was suboptimally controlled with oral combination therapy. Exenatide was associated with weight reduction and had a higher incidence of gastrointestinal adverse effects than insulin glargine.
*For members of the GWAA Study Group, see the Appendix.
Robert J. Heine, Luc F. Van Gaal, Don Johns, Michael J. Mihm, Mario H. Widel, Robert G. Brodows, et al. Exenatide versus Insulin Glargine in Patients with Suboptimally Controlled Type 2 Diabetes: A Randomized Trial. Ann Intern Med. 2005;143:559–569. doi: 10.7326/0003-4819-143-8-200510180-00006
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Published: Ann Intern Med. 2005;143(8):559-569.
Cardiology, Coronary Risk Factors, Diabetes, Endocrine and Metabolism.
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