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

• Published in: Endocrinology and metabolism (Seoul) Vol. 34; no. 1; pp. 80 - 92
• Main Authors: Bae, Jae Hyun, Kim, Sunhee, Park, Eun Gee, Kim, Sin Gon, Hahn, Seokyung, Kim, Nam Hoon
• Format: Journal Article
• Language: English
• Published: Korea (South) Korean Endocrine Society 01-03-2019; 대한내분비학회
• Subjects: Aged; Albumins - drug effects; Albuminuria; Albuminuria - prevention & control; Diabetes complications; Diabetes Complications - epidemiology; Diabetes Complications - prevention & control; Diabetes mellitus, type 2; Diabetes Mellitus, Type 2 - drug therapy; Diabetic nephropathies; Diabetic Nephropathies - epidemiology; Diabetic Nephropathies - prevention & control; Dipeptidyl-peptidase IV inhibitors; Dipeptidyl-Peptidase IV Inhibitors - administration & dosage; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Dipeptidyl-Peptidase IV Inhibitors - therapeutic use; Glomerular filtration rate; Glomerular Filtration Rate - drug effects; Humans; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Hypoglycemic Agents - therapeutic use; Kidney - drug effects; Kidney - physiopathology; Kidney failure, chronic; Kidney Failure, Chronic - etiology; Meta-analysis; Middle Aged; Original; Placebos - administration & dosage; Randomized Controlled Trials as Topic; Systematic review; 내과학; Diabetes complications; Diabetes mellitus, type 2; Dipeptidyl-peptidase IV inhibitors; Kidney failure, chronic; Diabetic nephropathies; Systematic review; Albuminuria; Glomerular filtration rate; Meta-analysis
• ISSN: 2093-596X; 2093-5978
• DOI: 10.3803/EnM.2019.34.1.80

To investigate the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on renal outcomes in patients with type 2 diabetes.
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.
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 (
=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;
=0.022) and macroalbuminuria (RR, 0.77; 95% CI, 0.61 to 0.97;
=0.027), as well as higher rates of regression of albuminuria (RR, 1.22; 95% CI, 1.10 to 1.35;
<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;
=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;
=0.475).
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.