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Diabetes Medications as Monotherapy or Metformin-Based Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-analysis

Nisa M. Maruthur, Eva Tseng, Susan M. Hutfless, Lisa M Wilson, Catalina Suarez‐Cuervo, Zackary Dov Berger, Yue Chu, Emmanuel Iyoha et al.

Annals of Internal Medicine, 2016

685 citations

Abstract

BACKGROUND: Clinicians and patients need updated evidence on the comparative effectiveness and safety of diabetes medications to make informed treatment choices. PURPOSE: To evaluate the comparative effectiveness and safety of monotherapy (thiazolidinediones, metformin, sulfonylureas, dipeptidyl peptidase-4 [DPP-4] inhibitors, sodium-glucose cotransporter 2 [SGLT-2] inhibitors, and glucagon-like peptide-1 [GLP-1] receptor agonists) and selected metformin-based combinations in adults with type 2 diabetes. DATA SOURCES: English-language studies from MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials, indexed from inception through March 2015 (MEDLINE search updated through December 2015). STUDY SELECTION: Paired reviewers independently identified 179 trials and 25 observational studies of head-to-head monotherapy or metformin-based combinations. DATA EXTRACTION: Two reviewers independently assessed study quality and serially extracted data and graded the strength of evidence. DATA SYNTHESIS: Cardiovascular mortality was lower for metformin versus sulfonylureas; the evidence on all-cause mortality, cardiovascular morbidity, and microvascular complications was insufficient or of low strength. Reductions in hemoglobin A1c values were similar across monotherapies and metformin-based combinations, except that DPP-4 inhibitors had smaller effects. Body weight was reduced or maintained with metformin, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT-2…

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