Saurav Chatterjee, MD
In adults with type 2 diabetes mellitus, are dipeptidyl peptidase-4 (DPP-4) inhibitors, alone or combined with metformin, effective and safe for glycemic control compared with metformin alone or combined with other hypoglycemic drugs?
Included studies compared DPP-4 inhibitors with metformin monotherapy, or DPP-4 inhibitors plus metformin with other hypoglycemic drugs (a sulfonylurea, basal insulin, pioglitazone, or a glucagon-like peptide [GLP]-1 agonist) plus metformin for ≥ 12 weeks in patients > 18 years of age with type 2 diabetes mellitus, and reported glycated hemoglobin (HbA1c) levels. Exclusion criteria were studies of rosiglitazone and hypoglycemic drugs not widely adopted in clinical practice (α-glucosidase inhibitors, glinides, amylin agonists), and pregnancy. Outcomes included changes in HbA1c levels and body weight, and adverse events.
MEDLINE, EMBASE/Excerpta Medica, Cochrane Library (all to 2011); conference abstracts from 3 professional associations (2009 and 2010); pharmaceutical company Web sites; ClinicalTrials.gov; and ClinicalStudyResults.org were searched for published and unpublished randomized controlled trials (RCTs). 27 reports of 19 RCTs (n = 13 881) met the selection criteria. 16 reports had adequate randomization, and 10 had adequate allocation concealment. Overall risk for bias for the primary outcome was low in 3 reports, unclear in 9, high in 14, and not assessed in 1.
DPP-4 inhibitor monotherapy resulted in smaller reductions in HbA1c than did metformin alone or than metformin plus a sulfonylurea or a GLP-1 agonist (Table). DPP-4 inhibitors increased weight compared with metformin alone or metformin plus a GLP-1 agonist but reduced weight compared with metformin plus a sulfonylurea or pioglitazone (Table). DPP-4 inhibitors plus metformin had a lower risk for serious adverse events than did metformin plus pioglitazone (relative risk reduction 53%, 95% CI 18 to 73) but did not differ from metformin plus a sulfonylurea or GLP-antagonist.
In adults with type 2 diabetes mellitus, dipeptidyl peptidase-4 (DPP-4) inhibitor monotherapy is less effective than metformin monotherapy for reducing HbA1c levels, and DPP-4 inhibitors plus metformin are less effective than metformin plus a sulfonylurea or a GLP-1 agonist.
DPP-4 inhibitors vs metformin (met) alone or DPP-4 inhibitors plus metformin vs metformin plus a sulfonylurea, pioglitazone, or a GLP-1 agonist in type 2 diabetes*
*DPP = dipeptidyl peptidase; GLP-1 = glucagon-like peptide-1; HbA1c = hemoglobin A1c; WMD = weighted mean difference; other abbreviations defined in Glossary. WMD based on a random-effects model.
†Values > 0 favor comparators.
Chatterjee S. Review: DPP-4 inhibitors are less effective than metformin for reducing HbA1c in type 2 diabetes. Ann Intern Med. ;157:JC1–13. doi: 10.7326/0003-4819-157-2-201207170-02013
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Published: Ann Intern Med. 2012;157(2):JC1-13.
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