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 Efficacy and Safety of Incretin Therapy in Type 2 Diabetes

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PostSubject: Efficacy and Safety of Incretin Therapy in Type 2 Diabetes   Fri Sep 21, 2007 12:07 am

Efficacy and Safety of Incretin Therapy in Type 2 Diabetes



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 A1c 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 A1c 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.
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