SGLT2 Inhibitor Plus DPP-4 Inhibitor as Combination Therapy for Type 2 Diabetes: A Systematic Review and Meta-Analysis

Diabetes Obes Metab. 2018 Aug;20(8):1972-1976. doi: 10.1111/dom.13294. Epub 2018 Apr 14.


To assess the efficacy and safety of sodium-glucose co-transporter 2 (SGLT2) inhibitors plus a dipeptidyl peptidase-4 (DPP-4) inhibitor in patients with type 2 diabetes mellitus (T2DM), we performed a systematic review and meta-analysis of 14 randomized controlled trials (RCTs) involving 4828 patients. Compared with a DPP-4 inhibitor, SGLT2 inhibitor/DPP-4 inhibitor combination therapy was significantly associated with a decrease in glycaemic control (HbA1c, -0.71%; fasting plasma glucose [FPG], -25.62 mg/dL; postprandial plasma glucose, -44.00 mg/dL), body weight (-2.05 kg) and systolic blood pressure (-5.90 mm Hg), but an increase in total cholesterol (TC) of 3.24%, high-density lipoprotein of 6.15% and low-density lipoprotein of 2.55%. Adding a DPP-4 inhibitor to an SGLT2 inhibitor could reduce HbA1c by -0.31%, FPG by -8.94 mg/dL, TC by -1.48% and triglycerides by -3.25%. Interestingly, low doses of an SGLT2 inhibitor in the combination has similar or even better efficacy in some aspects than high doses. Similar adverse events were observed for the combination therapy, with the exception of genital infection vs DPP-4 inhibitor (risk ratio [RR], 5.31) and consistent genital infection vs an SGLT2 inhibitor (RR, 0.61). Further studies are warranted to confirm these results.

Keywords: DPP-4 inhibitor; SGLT2 inhibitor; meta-analysis; type 2 diabetes.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects
  • Dipeptidyl-Peptidase IV Inhibitors / therapeutic use*
  • Drug Monitoring
  • Drug Therapy, Combination / adverse effects
  • Evidence-Based Medicine*
  • Humans
  • Hyperglycemia / prevention & control*
  • Hypoglycemia / chemically induced
  • Hypoglycemia / prevention & control*
  • Randomized Controlled Trials as Topic
  • Sodium-Glucose Transporter 2 Inhibitors / adverse effects
  • Sodium-Glucose Transporter 2 Inhibitors / therapeutic use*


  • Dipeptidyl-Peptidase IV Inhibitors
  • Sodium-Glucose Transporter 2 Inhibitors