Diabetes Care
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Buse, J. B.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Buse, J. B.
Social Bookmarking
Add to CiteULike   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
Diabetes Care 27:2628-2635, 2004
© 2004 by the American Diabetes Association, Inc.

Emerging Treatments and Technologies
Original Article

Effects of Exenatide (Exendin-4) on Glycemic Control Over 30 Weeks in Sulfonylurea-Treated Patients With Type 2 Diabetes

John B. Buse, MD, PHD1, Robert R. Henry, MD2, Jenny Han, MS3, Dennis D. Kim, MD3, Mark S. Fineman, BS3 and Alain D. Baron, MD3 for the Exenatide-113 Clinical Study Group*

1 Diabetes Care Center, University of North Carolina School of Medicine, Chapel Hill, North Carolina
2 Veterans Administration Medical Center, University of California, San Diego, California
3 Amylin Pharmaceuticals, San Diego, California

Address correspondence and reprint requests to Alain D. Baron, MD, Senior Vice-President, Clinical Research, Amylin Pharmaceuticals, 9360 Towne Centre Dr., Suite 110, San Diego, CA 92121. E-mail: abaron{at}amylin.com

OBJECTIVE—This study evaluated the ability of the incretin mimetic exenatide (exendin-4) to improve glycemic control in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea as monotherapy.

RESEARCH DESIGN AND METHODS—This was a triple-blind, placebo-controlled, 30-week study conducted at 101 sites in the U.S. After a 4-week, single-blind, placebo lead-in period, 377 subjects were randomized (60% men, age 55 ± 11 years, BMI 33 ± 6 kg/m2, HbA1c 8.6 ± 1.2% [±SD]) and began 4 weeks at 5 µg subcutaneous exenatide twice daily (before breakfast and dinner; arms A and B) or placebo. Subsequently, subjects in arm B were escalated to 10 µg b.i.d. exenatide. All subjects continued sulfonylurea therapy.

RESULTS—At week 30, HbA1c changes from baseline were –0.86 ± 0.11, –0.46 ± 0.12, and 0.12 ± 0.09% (±SE) in the 10-µg, 5-µg, and placebo arms, respectively (adjusted P < 0.001). Of evaluable subjects with baseline HbA1c > 7% (n = 237), 41% (10 µg), 33% (5 µg), and 9% (placebo) achieved HbA1c ≤ 7% (P < 0.001). Fasting plasma glucose concentrations decreased in the 10-µg arm compared with placebo (P < 0.05). Subjects in the exenatide arms had dose-dependent progressive weight loss, with an end-of-study loss in the 10-µg exenatide arm of –1.6 ± 0.3 kg from baseline (P < 0.05 vs. placebo). The most frequent adverse events were generally mild or moderate and gastrointestinal in nature. No severe hypoglycemia was observed.

CONCLUSIONS—Exenatide significantly reduced HbA1c in patients with type 2 diabetes failing maximally effective doses of a sulfonylurea. Exenatide was generally well tolerated and was associated with weight loss.

Abbreviations: GLP, glucagon-like peptide • ITT, intent to treat


Add to CiteULike CiteULike   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 Journal of the American Dental AssociationHome page
S. Kidambi and S. B. Patel
Diabetes Mellitus: Considerations for Dentistry
J Am Dent Assoc, October 1, 2008; 139(suppl_5): 8S - 18S.
[Abstract] [Full Text] [PDF]

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

Home page
 DiabetesHome page
K. M. Picha, M. R. Cunningham, D. J. Drucker, A. Mathur, T. Ort, M. Scully, A. Soderman, T. Spinka-Doms, V. Stojanovic-Susulic, B. A. Thomas, et al.
Protein Engineering Strategies for Sustained Glucagon-Like Peptide-1 Receptor-Dependent Control of Glucose Homeostasis
Diabetes, July 1, 2008; 57(7): 1926 - 1934.
[Abstract] [Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
E. Horton, W. T. Cefalu, S. T. Haines, and L. M. Siminerio
Multidisciplinary Interventions: Mapping New Horizons in Diabetes Care
The Diabetes Educator, July 1, 2008; 34(Supplement_4): 78S - 89S.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
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]

Home page
 The Diabetes EducatorHome page
R. K. Campbell and J. R. White Jr
More Choices Than Ever Before: Emerging Therapies for Type 2 Diabetes
The Diabetes Educator, May 1, 2008; 34(3): 518 - 534.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
M. Salehi, B. A. Aulinger, and D. A. D'Alessio
Targeting {beta}-Cell Mass in Type 2 Diabetes: Promise and Limitations of New Drugs Based on Incretins
Endocr. Rev., May 1, 2008; 29(3): 367 - 379.
[Abstract] [Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
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]

Home page
 Mol. Interv.Home page
S. R. Bloom, F. P. Kuhajda, I. Laher, X. Pi-Sunyer, G. V. Ronnett, T. M.M. Tan, and D. S. Weigle
The Obesity Epidemic: Pharmacological Challenges
Mol. Interv., April 1, 2008; 8(2): 82 - 98.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Pathol.Home page
L R Ranganath
Incretins: pathophysiological and therapeutic implications of glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1
J. Clin. Pathol., April 1, 2008; 61(4): 401 - 409.
[Abstract] [Full Text] [PDF]

Home page
 CJASNHome page
R. D. Bloom and M. F. Crutchlow
New-Onset Diabetes Mellitus in the Kidney Recipient: Diagnosis and Management Strategies
Clin. J. Am. Soc. Nephrol., March 1, 2008; 3(Supplement_2): S38 - S48.
[Abstract] [Full Text] [PDF]

Home page
 CirculationHome page
S. E. Inzucchi and D. K. McGuire
New Drugs for the Treatment of Diabetes: Part II: Incretin-Based Therapy and Beyond
Circulation, January 29, 2008; 117(4): 574 - 584.
[Abstract] [Full Text] [PDF]

Home page
 Clin. DiabetesHome page
M. J. Fowler
Diabetes Treatment, Part 3: Insulin and Incretins
Clin. Diabetes, January 1, 2008; 26(1): 35 - 39.
[Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
L. M. Siminerio
Approaches to Help People With Diabetes Overcome Barriers for Improved Health Outcomes
The Diabetes Educator, January 1, 2008; 34(1_suppl): 18S - 24S.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
N. A. Sherry, W. Chen, J. A. Kushner, M. Glandt, Q. Tang, S. Tsai, P. Santamaria, J. A. Bluestone, A.-M. B. Brillantes, and K. C. Herold
Exendin-4 Improves Reversal of Diabetes in NOD Mice Treated with Anti-CD3 Monoclonal Antibody by Enhancing Recovery of {beta}-Cells
Endocrinology, November 1, 2007; 148(11): 5136 - 5144.
[Abstract] [Full Text] [PDF]

Home page
 QJMHome page
H. Chahal and T.A. Chowdhury
Gliptins: a new class of oral hypoglycaemic agent
QJM, November 1, 2007; 100(11): 671 - 677.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
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]

Home page
 JAMAHome page
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]

Home page
 Diabetes Spectr.Home page
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]

Home page
 Pharmacol. Rev.Home page
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]

Home page
 Diabetes CareHome page
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]

Home page
 Endocr. Rev.Home page
B. E. Dunning and J. E. Gerich
The Role of {alpha}-Cell Dysregulation in Fasting and Postprandial Hyperglycemia in Type 2 Diabetes and Therapeutic Implications
Endocr. Rev., May 1, 2007; 28(3): 253 - 283.
[Abstract] [Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
S. T. Haines
Emerging Treatments for Patients With Type 2 Diabetes
The Diabetes Educator, May 1, 2007; 33(Supplement_5): 105S - 110S.
[Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
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]

Home page
 Endocr. Rev.Home page
B. L. Wajchenberg
{beta}-Cell Failure in Diabetes and Preservation by Clinical Treatment
Endocr. Rev., April 1, 2007; 28(2): 187 - 218.
[Abstract] [Full Text] [PDF]

Home page
 J EndocrinolHome page
T. H Claus, C. Q Pan, J. M Buxton, L. Yang, J. C Reynolds, N. Barucci, M. Burns, A. A Ortiz, S. Roczniak, J. N Livingston, et al.
Dual-acting peptide with prolonged glucagon-like peptide-1 receptor agonist and glucagon receptor antagonist activity for the treatment of type 2 diabetes
J. Endocrinol., February 1, 2007; 192(2): 371 - 380.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
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]

Home page
 Proc. Natl. Acad. Sci. USAHome page
K. G. Murphy and S. R. Bloom
Nonpeptidic glucagon-like peptide 1 receptor agonists: A magic bullet for diabetes?
PNAS, January 16, 2007; 104(3): 689 - 690.
[Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
S. A. McKennon and R. K. Campbell
The Physiology of Incretin Hormones and the Basis for DPP-4 Inhibitors
The Diabetes Educator, January 1, 2007; 33(1): 55 - 66.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
C. G. Parkin and J. A. Davidson
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: Response to Nathan et al.
Diabetes Care, January 1, 2007; 30(1): 192 - 193.
[Full Text] [PDF]

Home page
 Diabetes Spectr.Home page
L. E. John, M. P. Kane, R. S. Busch, and R. A. Hamilton
Expanded Use of Exenatide in the Management of Type 2 Diabetes
Diabetes Spectr, January 1, 2007; 20(1): 59 - 63.
[Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
R K. Campbell
Rationale for Dipeptidyl Peptidase 4 Inhibitors: A New Class of Oral Agents for the Treatment of Type 2 Diabetes Mellitus
Ann. Pharmacother., January 1, 2007; 41(1): 51 - 60.
[Abstract] [Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
A. L. Peters and D. Miller
Case Study 2: New Insights: Clinical Pearls for Using Incretin Mimetics in Type 2 Diabetes
The Diabetes Educator, January 1, 2007; 33(Supplement_1): 14S - 19S.
[Full Text] [PDF]

Home page
 Endocr. Rev.Home page
K. G. Murphy, W. S. Dhillo, and S. R. Bloom
Gut Peptides in the Regulation of Food Intake and Energy Homeostasis
Endocr. Rev., December 1, 2006; 27(7): 719 - 727.
[Abstract] [Full Text] [PDF]

Home page
 J Am Board Fam MedHome page
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]

Home page
 The Diabetes EducatorHome page
C. Carver
Insulin Treatment and the Problem of Weight Gain in Type 2 Diabetes
The Diabetes Educator, November 1, 2006; 32(6): 910 - 917.
[Abstract] [Full Text] [PDF]

Home page
 DOC NewsHome page
Overweight Patients a Good Fit for exenatide
DOC News, October 1, 2006; 3(10): 4 - 4.
[Full Text]

Home page
 J Clin PharmacolHome page
D. Soon, P. A. Kothare, H. Linnebjerg, S. Park, E. Yuen, K. F. Mace, and S. D. Wise
Effect of exenatide on the pharmacokinetics and pharmacodynamics of warfarin in healthy asian men.
J. Clin. Pharmacol., October 1, 2006; 46(10): 1179 - 1187.
[Abstract] [Full Text] [PDF]

Home page
 The Annals of PharmacotherapyHome page
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]

Home page
 The Diabetes EducatorHome page
P. S. Odegard, S. M. Setter, and J. L. Iltz
Update in the pharmacologic treatment of diabetes mellitus: focus on pramlintide and exenatide.
The Diabetes Educator, September 1, 2006; 32(5): 693 - 712.
[Abstract] [Full Text] [PDF]

Home page
 Diabetes CareHome page
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]

Home page
 Diabetes CareHome page
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]

Home page
 British Journal of Diabetes & Vascular DiseaseHome page
R. E Pratley, A. Salsali, and G. Matfin
Review: Inhibition of dipeptidyl peptidase-4 with vildagliptin: a potential new treatment for type 2 diabetes
The British Journal of Diabetes & Vascular Disease, July 1, 2006; 6(4): 150 - 156.
[Abstract] [PDF]

Home page
 Diabetes Spectr.Home page
R. Hood, V. Valentine, S. Mac, and W. H Polonsky
Use of Exenatide in Patients With Type 2 Diabetes
Diabetes Spectr, July 1, 2006; 19(3): 181 - 186.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. L. Baggio, D. Holland, J. Wither, and D. J. Drucker
Lymphocytic Infiltration and Immune Activation in Metallothionein Promoter-Exendin-4 (MT-Exendin) Transgenic Mice
Diabetes, June 1, 2006; 55(6): 1562 - 1570.
[Abstract] [Full Text] [PDF]

Home page
 Am J Health Syst PharmHome page
G. M. Bray
Exenatide
Am. J. Health Syst. Pharm., March 1, 2006; 63(5): 411 - 418.
[Abstract] [Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
D. J. Drucker
The evidence for achieving glycemic control with incretin mimetics.
The Diabetes Educator, March 1, 2006; 32(2 Suppl): 72S - 81S.
[Full Text] [PDF]

Home page
 The Diabetes EducatorHome page
L. Siminerio
Challenges and strategies for moving patients to injectable medications.
The Diabetes Educator, March 1, 2006; 32(2 Suppl): 82S - 90S.
[Full Text] [PDF]

Home page
 Diabetes CareHome page
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]

Home page
 J. Clin. Endocrinol. Metab.Home page
F. Fehse, M. Trautmann, J. J. Holst, A. E. Halseth, N. Nanayakkara, L. L. Nielsen, M. S. Fineman, D. D. Kim, and M. A. Nauck
Exenatide Augments First- and Second-Phase Insulin Secretion in Response to Intravenous Glucose in Subjects with Type 2 Diabetes
J. Clin. Endocrinol. Metab., November 1, 2005; 90(11): 5991 - 5997.
[Abstract] [Full Text] [PDF]

Home page
 ANN INTERN MEDHome page
R. J. Heine, L. F. Van Gaal, D. Johns, M. J. Mihm, M. H. Widel, R. G. Brodows, and for the GWAA Study Group*
Exenatide versus Insulin Glargine in Patients with Suboptimally Controlled Type 2 Diabetes: A Randomized Trial
Ann Intern Med, October 18, 2005; 143(8): 559 - 569.
[Abstract] [Full Text] [PDF]

Home page
 PhysiologyHome page
E. M Sinclair and D. J. Drucker
Proglucagon-Derived Peptides: Mechanisms of Action and Therapeutic Potential
Physiology, October 1, 2005; 20(5): 357 - 365.
[Abstract] [Full Text] [PDF]

Home page
 J Clin PharmacolHome page
P. A. Kothare, D. K. W. Soon, H. Linnebjerg, S. Park, C. Chan, A. Yeo, M. Lim, K. F. Mace, and S. D. Wise
Effect of Exenatide on the Steady-State Pharmacokinetics of Digoxin
J. Clin. Pharmacol., September 1, 2005; 45(9): 1032 - 1037.
[Abstract] [Full Text] [PDF]

Home page
 DOC NewsHome page
J. Hendry
FDA Approves Exenatide
DOC News, July 1, 2005; 2(7): 1 - 6.
[Full Text]

Home page
 British Journal of Diabetes & Vascular DiseaseHome page
C. A Schnabel
The incretin mimetic, exenatide: a novel treatment option for type 2 diabetes
The British Journal of Diabetes & Vascular Disease, July 1, 2005; 5(4): 227 - 235.
[Abstract] [PDF]

Home page
 JWatch GastroenterologyHome page
Exenatide, a New Drug for Type 2 Diabetes
Journal Watch Gastroenterology, June 14, 2005; 2005(614): 12 - 12.
[Full Text]

Home page
 Journal Watch CardiologyHome page
Exenatide, a New Drug for Type 2 Diabetes
Journal Watch Cardiology, June 10, 2005; 2005(610): 7 - 7.
[Full Text]

Home page
 JWatch GeneralHome page
Exenatide, a New Drug for Type 2 Diabetes
Journal Watch (General), May 24, 2005; 2005(524): 1 - 1.
[Full Text]