Hypoglycemics: Comparison of Clinical Outcomes and Adverse Events Associated With Glucose-Lowering Drugs in Patients With Type 2 Diabetes – JAMA July 16, 2016 – Volume 316, No. 3

Meta Analysis – evaluating glucose lowering drugs

  • Primary outcome: cardiovascular mortality
  • Secondary outcomes: all-cause mortality, serious adverse events, myocardial infarction, stroke, hemoglobin A1c (HbA1C) level, treatment failure (rescue treatment or lack of efficacy), hypoglycemia, and body weight
  • Tx time: 24 weeks or longer

Methods – 3o7 trials included

  • 177 monotherapy, 109 dual (metformin + other drug), 29 triple (metformin + sulfonylurea + other drug)


  • No significant differences in associations between any drug class as monotherapy, dual therapy, or triple therapy with odds of cardiovascular or all-cause mortality
  • Compared with metformin, sulfonylurea (standardized mean difference [SMD], 0.18 [95% CI, 0.01 to 0.34]), thiazolidinedione (SMD, 0.16 [95% CI, 0.00 to 0.31]), DPP-4 inhibitor (SMD, 0.33 [95% CI, 0.13 to 0.52]), and α-glucosidase inhibitor (SMD, 0.35 [95% CI, 0.12 to 0.58]) monotherapy were associated with higher HbA1C levels.


  • Monotherapy: Metformin first line, followed by any of the other agents
  • Use patient-centered tx when deciding 2nd line agent
  • ACC perspective: “This is a valuable study, albeit limited by disadvantages inherent to meta-analyses, which established that there are no differences in the associations between glucose-lowering drugs alone or in combination with odds of cardiovascular mortality, all-cause mortality, or myocardial infarction.


JAMA – Comparison of Clinical Outcomes/ADRs w/ Glucose Lowering Agents

ACC – Trial summary & perspective


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