The efficacy and safety of DPP4 inhibitors compared to sulfonylureas as add-on therapy to metformin in patients with Type 2 diabetes: A systematic review and meta-analysis

Diabetes Res Clin Pract. 2015 Aug;109(2):378-88. doi: 10.1016/j.diabres.2015.05.025. Epub 2015 May 14.


There is no consensus on the selection of specific drug therapies when metformin fails in Type 2 diabetes (T2D). This meta-analysis was performed to determine the efficacy and safety of Dipeptidyl peptidase-4 inhibitors (DPP4-I) compared to sulfonylurea (SU) as add-on therapy to metformin in inadequately controlled T2D patients. We searched MEDLINE, CENTRAL, EMBASE, and CINAHL for randomized trials comparing DPP4-I to SU as add-on therapy to metformin and reported a change in hemoglobin A1c (HbA1c). Sixteen articles were included. There was a significantly greater reduction in HbA1c from baseline to 12 weeks with SU versus DPP4-I (MD[95% CI]=0.21%(2 mmol/mol) [0.06, 0.35]) but no significant difference at 52 and 104 weeks (MD[95% CI]=0.06%(-1 mmol/mol) [-0.03, 0.15] and 0.02%(-1 mmol/mol) [-0.13,0.18] respectively). SU was associated with weight gain and DPP4-I with weight loss at all time-points. The incidence of hypoglycemia at 12, 52, and 104 weeks was significantly greater with SU (20%, 24%, and 27% respectively) compared to DPP4-I (6%, 3%, and 4% respectively). The proportion of patients with HbA1c<7%(53 mmol/mol) without hypoglycemia was significantly higher at 52 and 104 weeks among patients on DPP4-I (RR[95% CI]=1.20 [1.05, 1.37] and 1.53 [1.16, 2.02] respectively). There was no significant difference between the two groups in the incidence of other side effects. While both SU and DPP4-I can be considered as options for add-on therapy to metformin in inadequately controlled T2D, SU results in a significantly increased risk of hypoglycemia and weight gain. By contrast, DPP4-I produce 0.4-0.6% (4-7 mmol/mol) reduction in HbA1c, lower risk of hypoglycemia, and weight loss.

Keywords: DPP4-I; Meta-analysis; Metformin; Sulfonylurea; Type 2 diabetes.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Therapy, Combination
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Metformin / therapeutic use*
  • Sulfonylurea Compounds / therapeutic use*


  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • Metformin