This Article  • Full text  • PDF  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Citation map  • Citing articles on HighWire  • Citing articles on ISI (104)  • Contact me when this article is cited  Related Content  • Related letters  • Similar articles in JAMA  Topic Collections  • Quality of Care  • Evidence-Based Medicine  • Women's Health, Other  • Review  • Drug Therapy, Other  • Diabetes Mellitus  • Alert me on articles by topic  Social Bookmarking   What's this?

Systematic Review and Meta-analysis

Renee E. Amori, MD; Joseph Lau, MD; Anastassios G. Pittas, MD, MSc

JAMA. 2007;298:194-206.

Context  Pharmacotherapies that augment the incretin pathway have recently become available, but their role in the management of type 2 diabetes is not well defined.

Objective  To assess the efficacy and safety of incretin-based therapy in adults with type 2 diabetes based on randomized controlled trials published in peer-reviewed journals or as abstracts.

Data Sources  We searched MEDLINE (1966–May 20, 2007) and the Cochrane Central Register of Controlled Trials (second quarter, 2007) for English-language randomized controlled trials involving an incretin mimetic (glucagonlike peptide 1 [GLP-1] analogue) or enhancer (dipeptidyl peptidase 4 [DPP4] inhibitor). We also searched prescribing information, relevant Web sites, reference lists and citation sections of recovered articles, and abstracts presented at recent conferences.

Study Selection  Randomized controlled trials were selected if they were at least 12 weeks in duration, compared incretin therapy with placebo or other diabetes medication, and reported hemoglobin A_1c data in nonpregnant adults with type 2 diabetes.

Data Extraction  Two reviewers independently assessed trials for inclusion and extracted data. Differences were resolved by consensus. Meta-analyses were conducted for several efficacy and safety outcomes.

Results  Of 355 potentially relevant articles identified, 51 were retrieved for detailed evaluation and 29 met the inclusion criteria. Incretins lowered hemoglobin A_1c compared with placebo (weighted mean difference, –0.97% [95% confidence interval {CI}, –1.13% to –0.81%] for GLP-1 analogues and –0.74% [95% CI, –0.85% to –0.62%] for DPP4 inhibitors) and were noninferior to other hypoglycemic agents. Glucagonlike peptide 1 analogues resulted in weight loss (1.4 kg and 4.8 kg vs placebo and insulin, respectively) while DPP4 inhibitors were weight neutral. Glucagonlike peptide 1 analogues had more gastrointestinal side effects (risk ratio, 2.9 [95% CI, 2.0-4.2] for nausea and 3.2 [95% CI, 2.5-4.4] for vomiting). Dipeptidyl peptidase 4 inhibitors had an increased risk of infection (risk ratio, 1.2 [95% CI, 1.0-1.4] for nasopharyngitis and 1.5 [95% CI, 1.0-2.2] for urinary tract infection) and headache (risk ratio, 1.4 [95% CI, 1.1-1.7]). All but 3 trials had a 30-week or shorter duration; thus, long-term efficacy and safety could not be evaluated.

Conclusions  Incretin therapy offers an alternative option to currently available hypoglycemic agents for nonpregnant adults with type 2 diabetes, with modest efficacy and a favorable weight-change profile. Careful postmarketing surveillance for adverse effects, especially among the DPP4 inhibitors, and continued evaluation in longer-term studies and in clinical practice are required to determine the role of this new class among current pharmacotherapies for type 2 diabetes.

Author Affiliations: Division of Endocrinology, Diabetes and Metabolism (Drs Amori and Pittas) and Institute for Clinical Research and Health Policy Studies (Dr Lau), Tufts-New England Medical Center, Boston, Massachusetts.

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

RELATED LETTERS

Adverse Effects of Incretin Therapy for Type 2 Diabetes
Eric Grouzmann, Michel Monod, Basil N. Landis, and Jean-Silvain Lacroix
JAMA. 2007;298(15):1759-1760.
EXTRACT | FULL TEXT  

Adverse Effects of Incretin Therapy for Type 2 Diabetes—Reply
Anastassios G. Pittas, Renee E. Amori, and Joseph Lau
JAMA. 2007;298(15):1760.
EXTRACT | FULL TEXT  

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

Pharmacokinetics of the Dipeptidyl Peptidase 4 Inhibitor Saxagliptin in Rats, Dogs, and Monkeys and Clinical Projections
Fura et al.
Drug Metab. Dispos. 2009;37:1164-1171.
ABSTRACT | FULL TEXT  

Glucagon-like peptide-1 receptor agonists in type 2 diabetes: a meta-analysis of randomized clinical trials
Monami et al.
Eur J Endocrinol 2009;160:909-917.
ABSTRACT | FULL TEXT  

Current Therapeutic Drugs for Type 2 Diabetes, Still Useful After 50 Years?
Hall and Nicholson
Anesth. Analg. 2009;108:1727-1730.
FULL TEXT  

New Therapeutic Agents for Diabetes Mellitus: Implications for Anesthetic Management
Chen et al.
Anesth. Analg. 2009;108:1803-1810.
ABSTRACT | FULL TEXT  

Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes
Nathan et al.
Clin. Diabetes 2009;27:4-16.
FULL TEXT  

Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes
Nathan et al.
Diabetes Spectr. 2009;22:6-17.
FULL TEXT  

Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy: A consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes
Nathan et al.
Diabetes Care 2009;32:193-203.
ABSTRACT | FULL TEXT  

Expanding Treatment Options for Type 2 Diabetes: The Old and the New
Pratley
The Diabetes Educator 2009;35:4S-11S.
ABSTRACT | FULL TEXT  

The Therapeutic Role of Incretin Mimetics and DPP-4 Inhibitors
Funnell
The Diabetes Educator 2009;35:12S-17S.
ABSTRACT | FULL TEXT  

The Role of Incretins in Glucose Homeostasis and Diabetes Treatment
Kim and Egan
Pharmacol. Rev. 2008;60:470-512.
ABSTRACT | FULL TEXT  

Pharmacology of GLP-1-based therapies
Holst
British Journal of Diabetes & Vascular Disease 2008;8:S10-S18.
ABSTRACT  

SERENADE: The Study Evaluating Rimonabant Efficacy in Drug-Naive Diabetic Patients: Effects of monotherapy with rimonabant, the first selective CB1 receptor antagonist, on glycemic control, body weight, and lipid profile in drug-naive type 2 diabetes
Rosenstock et al.
Diabetes Care 2008;31:2169-2176.
ABSTRACT | FULL TEXT  

Incretin-Based Therapies in Type 2 Diabetes Mellitus
Chia and Egan
J. Clin. Endocrinol. Metab. 2008;93:3703-3716.
ABSTRACT | FULL TEXT  

Recent advances in the management of type 2 diabetes mellitus: a review
Srinivasan et al.
Postgrad. Med. J. 2008;84:524-531.
ABSTRACT | FULL TEXT  

Diabetes Mellitus--A Call for Papers
DeAngelis et al.
JAMA 2008;300:441-441.
FULL TEXT  

Three new drugs for type 2 diabetes
DTB 2008;46:49-52.
ABSTRACT | FULL TEXT  

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?
Van Gaal et al.
Eur J Endocrinol 2008;158:773-784.
ABSTRACT | FULL TEXT  

{beta}-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic {beta} cells
Sonoda et al.
Proc. Natl. Acad. Sci. USA 2008;105:6614-6619.
ABSTRACT | FULL TEXT  

Targeting {beta}-Cell Mass in Type 2 Diabetes: Promise and Limitations of New Drugs Based on Incretins
Salehi et al.
Endocr. Rev. 2008;29:367-379.
ABSTRACT | FULL TEXT  

New Drugs for the Treatment of Diabetes: Part II: Incretin-Based Therapy and Beyond
Inzucchi and McGuire
Circulation 2008;117:574-584.
ABSTRACT | FULL TEXT  

Is Dipeptidylpeptidase IV the Missing Link in Angiotensin-Converting Enzyme Inhibitor Induced Angioedema?
Grouzmann and Buclin
Hypertension 2008;51:45-47.
FULL TEXT  

Peptide YY: obesity's cause and cure?
Tschop and Ravussin
Am. J. Physiol. Endocrinol. Metab. 2007;293:E1131-E1133.
FULL TEXT  

Adverse Effects of Incretin Therapy for Type 2 Diabetes
Grouzmann et al.
JAMA 2007;298:1759-1760.
FULL TEXT  

Incretins Prove Comparable to Older Therapies
Stacy
DOC News 2007;4:1-13.
FULL TEXT