Comparative Renal Effects of Dipeptidyl Peptidase-4 Inhibitors and Sodium-Glucose Cotransporter 2 Inhibitors on Individual Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Network Meta-Analysis

Abstract

Background: To compare the renal effects of dipeptidyl peptidase-4 (DPP-4) inhibitors and sodium-glucose cotransporter 2 (SGLT2) inhibitors on individual outcomes in patients with type 2 diabetes.

Methods: We searched electronic databases (MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials) from inception to June 2019 to identity eligible randomized controlled trials of DPP-4 inhibitors or SGLT2 inhibitors that reported at least one kidney outcome in patients with type 2 diabetes. Outcomes of interest were microalbuminuria, macroalbuminuria, worsening nephropathy, and end-stage kidney disease (ESKD). We performed an arm-based network meta-analysis using Bayesian methods and calculated absolute risks and rank probabilities of each treatment for the outcomes.

Results: Seventeen studies with 87,263 patients were included. SGLT2 inhibitors significantly lowered the risks of individual kidney outcomes, including microalbuminuria (odds ratio [OR], 0.64; 95% credible interval [CrI], 0.41 to 0.93), macroalbuminuria (OR, 0.48; 95% CrI, 0.24 to 0.72), worsening nephropathy (OR, 0.65; 95% CrI, 0.44 to 0.91), and ESKD (OR, 0.65; 95% CrI, 0.46 to 0.98) as compared with placebo. However, DPP-4 inhibitors did not lower the risks. SGLT2 inhibitors were considerably associated with higher absolute risk reductions in all kidney outcomes than DPP-4 inhibitors, although the benefits were statistically insignificant. The rank probabilities showed that SGLT2 inhibitors were better treatments for lowering the risk of albuminuria and ESKD than placebo or DPP-4 inhibitors.

Conclusion: SGLT2 inhibitors were superior to DPP-4 inhibitors in reducing the risk of albuminuria and ESKD in patients with type 2 diabetes.

Keywords: Albuminuria; Diabetes mellitus, type 2; Diabetic nephropathies; Dipeptidyl-peptidase IV inhibitors; Kidney failure, chronic; Network meta-analysis; Sodium-glucose transporter 2 inhibitors.

Fig. 1

Network of the treatment comparisons for (A) microalbuminuria, macroalbuminuria, worsening nephropathy, and (B) end-stage kidney disease. Node size is proportional to the number of studies. Lines indicate direct comparisons between the treatments, and their thickness corresponds to the number of studies in each comparison. DPP-4, dipeptidyl peptidase-4; SGLT2, sodium-glucose cotransporter 2.

Fig. 2

Absolute risks and rank probabilities of the treatments for (A) microalbuminuria, (B) macroalbuminuria, (C) worsening nephropathy, and (D) end-stage kidney disease. Ranking (no. 1 to no. 3) represents the best, second best, and third best treatment for reducing the risk of each outcome, respectively. DPP-4i, dipeptidyl peptidase-4 inhibitor; SGLT2i, sodium-glucose cotransporter 2 inhibitor.