A review of the latest evidence regarding type 2 diabetes treatment, supports current guidelines which recommend metformin as a first-line therapy.  The study, published online in the Annals of Internal Medicine, looked at 179 trials and 25 observational studies to evaluate the comparative effectiveness and safety of the most common monotherapies and combination therapies used in the treatment of type 2 diabetes. Therapies included in this investigation included metformin, thiazolidinediones, sulfonylureas, dipeptidyl peptidase (DPP-4) inhibitors, sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. Treatments were assessed for both efficacy and safety outcomes.

All-Cause Mortality, Macrovascular and Microvascular Outcomes

  • Compared to sulfonylurea monotherapy, metformin monotherapy was associated with lower long-term cardiovascular mortality (Moderate strength)
  • Compared to sulfonylureas, metformin was associated with lower risk of all-cause mortality and cardiovascular morbidity (Low strength)
  • Insufficient or low strength evidence for all other drug comparisons

Hemoglobin A1C

  • In the short term, metformin, thiazolidinedione, and sulfonylurea monotherapy lowered HbA1C to a similar degree
  • DPP-4 inhibitors were less effective than metformin or sulfonylureas
  • Metformin + GLP-1 receptor agonist reduced HbA1C more than metformin + DPP-4 inhibitors, otherwise most combinations had no clinically meaningful between-group differences

Body Weight

  • Metformin decreased weight more than DPP-4 inhibitors
  • SGLT-2 inhibitors reduced weight more than metformin or DPP-4 inhibitors
  • Increases in weight were seen with sulfonylureas, thiazolidinediones, and insulin