Article    Table of Contents                    Full Text of this article    PDF of this article (PDFs free after 6 months)    Summary for Patients    Summary for Patients (PDF)    Figures/Tables List    Video News Release    Related articles in Annals  Services    Send comment/rapid response letter    Published comments/rapid response letters    Notify a friend about this article    Alert me when this article is cited    Add to Personal Archive    Download to Citation Manager    ACP Search                            Get Permissions  Google Scholar    Search for Related Content  PubMed Articles in PubMed by Author:    Heine, R. J.    Related Articles in PubMed    PubMed Citation    PubMed

ARTICLE

Exenatide versus Insulin Glargine in Patients with Suboptimally Controlled Type 2 Diabetes

A Randomized Trial

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*

18 October 2005 | Volume 143 Issue 8 | Pages 559-569

Background: 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.

Objective: 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.

Design: 26-week multicenter, open-label, randomized, controlled trial.

Setting: 82 outpatient study centers in 13 countries.

Patients: 551 patients with type 2 diabetes and inadequate glycemic control (defined as hemoglobin A_1c level ranging from 7.0% to 10.0%) despite combination metformin and sulfonylurea therapy.

Intervention: 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).

Measurements: Hemoglobin A_1c level, fasting plasma glucose level, body weight, 7-point self-monitored blood glucose, standardized test-meal challenge, safety, and tolerability.

Results: Baseline mean hemoglobin A_1c 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 A_1c 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%).

Limitations: 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).

Conclusions: 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.

Editors' Notes Context Are both exenatide and insulin glargine reasonable additions for patients with type 2 diabetes that is suboptimally controlled despite metformin and sulfonylurea therapy? Contribution This multicenter, 26-week, randomized trial compared the addition of exenatide or insulin glargine to regimens of 551 patients with suboptimally controlled type 2 diabetes. Both additions led to similar reductions in hemoglobin A1c levels. Exenatide best reduced postprandial glucose excursions; insulin glargine best reduced fasting glucose concentrations. Exenatide patients experienced weight loss and increased gastrointestinal symptoms, such as nausea and vomiting. Implications Adding either exenatide or insulin glargine to oral hypoglycemic regimens may improve glycemic control in patients with suboptimally controlled type 2 diabetes. —The Editors

 

Author and Article Information

From VU University Medical Center, Amsterdam, the Netherlands; University Hospital of Antwerp, Antwerp, Belgium; and Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana.

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.

Related articles in Annals:

Articles
Inhaled Insulin Improves Glycemic Control When Substituted for or Added to Oral Combination Therapy in Type 2 Diabetes: A Randomized, Controlled Trial
Julio Rosenstock, Bernard Zinman, Liam J. Murphy, Stephen C. Clement, Paul Moore, C. Keith Bowering, Rosa Hendler, Shu-Ping Lan, AND William T. Cefalu

Annals 2005 143: 549-558. [ABSTRACT][SUMMARY][Full Text]  

Editorials
Treatment of Type 2 Diabetes Mellitus: A Weighty Enigma
Richard J. Comi

Annals 2005 143: 609-610. [Full Text]  

Summaries for Patients
Exenatide or Insulin Glargine for Suboptimally Controlled Diabetes?

Annals 2005 143: I-30. [Full Text]  

This article has been cited by other articles:

				Three new drugs for type 2 diabetes DTB, July 1, 2008; 46(7): 49 - 52. [Abstract] [Full Text] [PDF]

				L. F Van Gaal, S. W Gutkin, and M. A Nauck Exploiting the antidiabetic properties of incretins to treat type 2 diabetes mellitus: glucagon-like peptide 1 receptor agonists or insulin for patients with inadequate glycemic control? Eur. J. Endocrinol., June 1, 2008; 158(6): 773 - 784. [Abstract] [Full Text] [PDF]

				P. Cure, A. Pileggi, R. Alejandro, S. R. Ahmad, J. Swann, G. Bloomgren, D. Braun, and O. Kolterman Exenatide and Rare Adverse Events N. Engl. J. Med., May 1, 2008; 358(18): 1969 - 1972. [Full Text] [PDF]

				C. L. Martin Beyond Glycemic Control: The Effects of Incretin Hormones in Type 2 Diabetes The Diabetes Educator, May 1, 2008; 34(Supplement_3): 66S - 72S. [Abstract] [Full Text] [PDF]

				L. Monnier and C. Colette Glycemic Variability: Should we and can we prevent it? Diabetes Care, February 1, 2008; 31(Supplement_2): S150 - S154. [Abstract] [Full Text] [PDF]

				J. B. Dixon, P. E. O'Brien, J. Playfair, L. Chapman, L. M. Schachter, S. Skinner, J. Proietto, M. Bailey, and M. Anderson Adjustable Gastric Banding and Conventional Therapy for Type 2 Diabetes: A Randomized Controlled Trial JAMA, January 23, 2008; 299(3): 316 - 323. [Abstract] [Full Text] [PDF]

				Management of Type 2 Diabetes N. Engl. J. Med., January 17, 2008; 358(3): 293 - 297. [Full Text] [PDF]

				S. N. Davis, D. Johns, D. Maggs, H. Xu, J. H. Northrup, and R. G. Brodows Exploring the Substitution of Exenatide for Insulin in Patients With Type 2 Diabetes Treated With Insulin in Combination With Oral Antidiabetes Agents Diabetes Care, November 1, 2007; 30(11): 2767 - 2772. [Abstract] [Full Text] [PDF]

				M. H. Tschop and E. Ravussin Peptide YY: obesity's cause and cure? Am J Physiol Endocrinol Metab, November 1, 2007; 293(5): E1131 - E1133. [Full Text] [PDF]

				Z. T. Bloomgarden Exploring Treatment Strategies for Type 2 Diabetes Diabetes Care, October 1, 2007; 30(10): 2737 - 2745. [Full Text] [PDF]

				R. J. Heine, R. Brodows, E. G. Maderazo, D. Tarsy, and M. Camilleri Diabetic Gastroparesis N. Engl. J. Med., July 26, 2007; 357(4): 418 - 420. [Full Text] [PDF]

				R. E. Amori, J. Lau, and A. G. Pittas Efficacy and Safety of Incretin Therapy in Type 2 Diabetes: Systematic Review and Meta-analysis JAMA, July 11, 2007; 298(2): 194 - 206. [Abstract] [Full Text] [PDF]

				P. Hollander Anti-Diabetes and Anti-Obesity Medications: Effects on Weight in People With Diabetes Diabetes Spectr, July 1, 2007; 20(3): 159 - 165. [Abstract] [Full Text] [PDF]

				G. A. Bray and F. L. Greenway Pharmacological Treatment of the Overweight Patient Pharmacol. Rev., June 1, 2007; 59(2): 151 - 184. [Full Text] [PDF]

				D. Kim, L. MacConell, D. Zhuang, P. A. Kothare, M. Trautmann, M. Fineman, and K. Taylor Effects of Once-Weekly Dosing of a Long-Acting Release Formulation of Exenatide on Glucose Control and Body Weight in Subjects With Type 2 Diabetes Diabetes Care, June 1, 2007; 30(6): 1487 - 1493. [Abstract] [Full Text] [PDF]

				C. N. Andrews, A. E. Bharucha, M. Camilleri, P. A. Low, B. Seide, D. Burton, K. Baxter, and A. R. Zinsmeister Nitrergic contribution to gastric relaxation induced by glucagon-like peptide-1 (GLP-1) in healthy adults Am J Physiol Gastrointest Liver Physiol, May 1, 2007; 292(5): G1359 - G1365. [Abstract] [Full Text] [PDF]

				B. Zinman, B. J. Hoogwerf, S. Duran Garcia, D. R. Milton, J. M. Giaconia, D. D. Kim, M. E. Trautmann, and R. G. Brodows The Effect of Adding Exenatide to a Thiazolidinedione in Suboptimally Controlled Type 2 Diabetes: A Randomized Trial Ann Intern Med, April 3, 2007; 146(7): 477 - 485. [Abstract] [Full Text] [PDF]

				D. F. Kruger Tying It All Together: Matching Insulin Regimens to Individual Patient Needs The Diabetes Educator, April 1, 2007; 33(Supplement_4): 91S - 95S. [Full Text] [PDF]

				M. Camilleri Diabetic Gastroparesis N. Engl. J. Med., February 22, 2007; 356(8): 820 - 829. [Full Text] [PDF]

				J. de Heer and J. J. Holst Sulfonylurea Compounds Uncouple the Glucose Dependence of the Insulinotropic Effect of Glucagon-Like Peptide 1 Diabetes, February 1, 2007; 56(2): 438 - 443. [Abstract] [Full Text] [PDF]

				R J Heine, M Diamant, J-C Mbanya, and D M Nathan Management of hyperglycaemia in type 2 diabetes: the end of recurrent failure? BMJ, December 9, 2006; 333(7580): 1200 - 1204. [Full Text] [PDF]

				D. Hinnen, L. L. Nielsen, A. Waninger, and P. Kushner Incretin Mimetics and DPP-IV Inhibitors: New Paradigms for the Treatment of Type 2 Diabetes J Am Board Fam Med, November 1, 2006; 19(6): 612 - 620. [Abstract] [Full Text] [PDF]

				B. K. Yoo, D. M. Triller, and D. J. Yoo Exenatide: A New Option for the Treatment of Type 2 Diabetes Ann. Pharmacother., October 1, 2006; 40(10): 1777 - 1784. [Abstract] [Full Text] [PDF]

				D. M. Nathan, J. B. Buse, M. B. Davidson, R. J. Heine, R. R. Holman, R. Sherwin, and B. Zinman Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes Diabetes Care, August 1, 2006; 29(8): 1963 - 1972. [Full Text] [PDF]

				A. B. King, G. Wolfe, and S. Healy Clinical Observations of Exenatide Treatment Diabetes Care, August 1, 2006; 29(8): 1984 - 1984. [Full Text] [PDF]

				M. C. Riddle and D. J. Drucker Emerging Therapies Mimicking the Effects of Amylin and Glucagon-Like Peptide 1 Diabetes Care, February 1, 2006; 29(2): 435 - 449. [Full Text] [PDF]

				E. T. Beckley Exenatide Rivals Glargine for A1C Control DOC News, December 1, 2005; 2(12): 7 - 7. [Full Text]

				Endocrinology & Metabolism News, December 2005 J. Clin. Endocrinol. Metab., December 1, 2005; 90(12): 17a - 17a. [Full Text] [PDF]

				New Treatments for Uncontrolled Diabetes Journal Watch (General), October 25, 2005; 2005(1025): 1 - 1. [Full Text]

				R. J. Comi Treatment of Type 2 Diabetes Mellitus: A Weighty Enigma Ann Intern Med, October 18, 2005; 143(8): 609 - 610. [Full Text] [PDF]

Rapid Responses: