Head-to-head comparison of dipeptidyl peptidase-IV inhibitors and sulfonylureas - a meta-analysis from randomized clinical trials

Diabetes Metab Res Rev. 2014 Mar;30(3):241-56. doi: 10.1002/dmrr.2482.


Background: Dipeptidyl peptidase-IV (DPP-4) inhibitors and sulfonylureas are two important second-line anti-diabetic agents. The objective of this research was to evaluate the efficacy and safety of DPP-4 inhibitors compared with sulfonylureas by meta-analytic approach of available randomized studies.

Methods: We searched MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials databases up to 30 June 2013, collecting all randomized clinical trials with a treatment duration of ≥18weeks. Data on glycated haemoglobin (HbA1c ), body weight, hypoglycaemia, total adverse events, and cardiovascular events were retrieved and analysed.

Results: The analysis included 12 randomized studies comprising 10 982 patients with type 2 diabetes mellitus. On the basis of meta-analysis, sulfonylureas lowered HbA1c significantly more than DPP-4 inhibitors with weighted mean difference (WMD) of 0.105 [95% confidence interval (CI) 0.103 to 0.107]. The results were consistent in trials with longer (>32 weeks) or shorter (≤32 weeks) duration; however, DPP-4 inhibitors showed greater reduction in HbA1c compared with the second-generation sulfonylureas and in patients with baseline eGFR < 50 mL/min/1.73 m(2) . Patients treated with DPP-4 inhibitors are less likely to achieve HbA1c < 7% compared with sulfonylureas [Mantel-Haenszel odds ratio (MH-OR) 0.91; 95% CI 0.84 to 0.99]. DPP-4 xinhibitors were associated with a reduction in body weight (WMD -1.652; 95% CI -1.658 to -1.646) and lower risk of hypoglycaemia (MH-OR, 0.13; 95% CI 0.11 to 0.16), total adverse events (MH-OR, 0.79; 95% CI 0.72 to 0.87), and cardiovascular events (MH-OR, 0.53; 95% CI 0.32 to 0.87) compared with sulfonylureas.

Conclusion: Although DPP-4 inhibitors are less efficacious compared with sulfonylureas, they demonstrate a beneficial effect on body weight, episodes of hypoglycaemia, and total adverse events.

Keywords: body weight; dipeptidyl peptidase-IV; efficacy; hypoglycaemia; safety; sulfonylureas; type 2 diabetes.

Publication types

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

MeSH terms

  • Confidence Intervals
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Glomerular Filtration Rate / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Odds Ratio
  • Randomized Controlled Trials as Topic
  • Sulfonylurea Compounds / adverse effects
  • Sulfonylurea Compounds / therapeutic use*


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