Endocrinol Metab.  2019 Mar;34(1):80-92. 10.3803/EnM.2019.34.1.80.

Effects of Dipeptidyl Peptidase-4 Inhibitors on Renal Outcomes in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

• Bae JH
• Kim S
• Park EG
• Kim SG
• Hahn S
• Kim NH

• KMID: 2441682
• DOI: http://doi.org/10.3803/EnM.2019.34.1.80

Abstract

BACKGROUND
To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes.
METHODS
MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched to identify randomized controlled trials (RCTs) of DPP-4 inhibitors from inception to September 2017. We selected eligible RCTs comparing DPP-4 inhibitors with placebo or other antidiabetic agents and reporting at least one renal outcome. A meta-analysis was conducted to calculate standardized mean differences, weighted mean differences (WMDs), relative risks (RRs), and 95% confidence intervals (CIs) for each renal outcome.
RESULTS
We included 23 RCTs with 19 publications involving 41,359 patients. Overall changes in urine albumin-to-creatinine ratio were comparable between DPP-4 inhibitors and controls (P=0.150). However, DPP-4 inhibitors were associated with significantly lower risk of incident microalbuminuria (RR, 0.89; 95% CI, 0.80 to 0.98; P=0.022) and macroalbuminuria (RR, 0.77; 95% CI, 0.61 to 0.97; P=0.027), as well as higher rates of regression of albuminuria (RR, 1.22; 95% CI, 1.10 to 1.35; P<0.001) compared with controls. Although DPP-4 inhibitors were associated with small but significantly lower estimated glomerular filtration rate (WMD, −1.11 mL/min/1.73 m2; 95% CI, −1.78 to −0.44; P=0.001), there was no difference in the risk of end-stage renal disease between two groups (RR, 0.93; 95% CI, 0.76 to 1.14; P=0.475).
CONCLUSION
DPP-4 inhibitors had beneficial renal effects mainly by reducing the risk of development or progression of albuminuria compared with placebo or other antidiabetic agents.

Keyword

Albuminuria; Diabetes complications; Diabetes mellitus, type 2; Diabetic nephropathies; Dipeptidyl-peptidase IV inhibitors; Glomerular filtration rate; Kidney failure, chronic; Meta-analysis; Systematic review

MeSH Terms

Albuminuria
Diabetes Complications
Diabetes Mellitus, Type 2
Diabetic Nephropathies
Dipeptidyl-Peptidase IV Inhibitors
Glomerular Filtration Rate
Humans
Hypoglycemic Agents
Kidney Failure, Chronic
Dipeptidyl-Peptidase IV Inhibitors
Hypoglycemic Agents

Figure

• 

  Fig. 1 Flow diagram of study screening and selection process.

• 

  Fig. 2 Standardized mean differences in changes in urine albumin-to-creatinine ratio (UACR) from baseline (mg/g) for dipeptidyl peptidase-4 (DPP-4) inhibitors versus placebo or other antidiabetic agents, according to non-sodium-glucose cotransporter 2 inhibitors and sodium-glucose cotransporter 2 inhibitors in the control group. Trt, treatment group; Con, control group; SD, standard deviation; ES, effect size; CI, confidence interval; SGLT2, sodium-glucose cotransporter 2; OHA, oral hypoglycemic agent; NR, not reported.

• 

  Fig. 3 Weighted mean differences in changes in estimated glomerular filtration rate from baseline (mL/min/1.73 m2) for dipeptidyl peptidase-4 (DPP-4) inhibitors versus placebo or other antidiabetic agents. Trt, treatment group; Con, control group; SD, standard deviation; ES, effect size; CI, confidence interval; NR, not reported.

• 

  Fig. 4 Relative risks of incident albuminuria, regression of albuminuria, and end-stage renal disease for dipeptidyl peptidase-4 (DPP-4) inhibitors versus placebo or other antidiabetic agents. (A) Microalbuminuria, (B) macroalbuminuria, (C) regression of albuminuria, and (D) end-stage renal disease. Trt, treatment group; Con, control group; RR, relative risk; CI, confidence interval.

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