Choosing First-Line Drugs for T2DM

Systematic review and meta-analysis of 204 studies.
81% were RCTs
Moderate-strength:  metformin monotherapy -> lower long-term CV-related mortality than SU monotherapy (RR 0.65)
But, low or no evidence for differences in all-cause mortality and macro/microvascular outcomes.
DPP-4 inhibitors < metformin/SU for A1c lowering
Metformin + almost anything -> similar A1c lowering, except DPP-4 + met (not as good) and GLP-1 + met (even less good).
Weight stable or decreased on:  metformin, DPP-4, GLP-1, SGLT-2s.
Weight increased with:  SU, TZDs, insulin
SUs highest risk for hypoglycemia.
SGLT-2s highest risk for vaginal yeast infections.
NO INCREASED RISK for lactic acidosis with metformin!
Conclusion:  metformin is still first line.  Metformin contraindicated if eGFR < 30, use caution if 30-45.
Ann Intern Med 2016 Apr 19
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