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The effects of dipeptidyl peptidase‐4 inhibitors on kidney outcomes
Author(s) -
O'Hara Daniel V.,
Parkhill Thomas R.,
Badve Sunil V.,
Jun Min,
Jardine Meg J.,
Perkovic Vlado
Publication year - 2021
Publication title -
diabetes, obesity and metabolism
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.445
H-Index - 128
eISSN - 1463-1326
pISSN - 1462-8902
DOI - 10.1111/dom.14281
Subject(s) - medicine , placebo , relative risk , confidence interval , renal function , linagliptin , randomized controlled trial , kidney disease , meta analysis , dipeptidyl peptidase 4 , creatinine , vildagliptin , diabetes mellitus , type 2 diabetes , endocrinology , pathology , alternative medicine
Abstract Aims To summarize evidence from randomized controlled trials (RCTs) concerning the effects of dipeptidyl peptidase‐4 (DPP‐4) inhibitors on kidney outcomes in patients with type 2 diabetes mellitus (T2DM). Methods The Medline, EMBASE and Cochrane databases were searched for RCTs comparing DPP‐4 inhibitors with a placebo, active comparator or standard care, with at least 500 person‐years follow‐up in patients with T2DM and with reporting of kidney outcomes. Treatment effects were summarized using random‐effects meta‐analysis. Results Ten trials including 47 955 patients (mean estimated glomerular filtration rate [eGFR] 71 mL/min/1.73m 2 , mean follow‐up 10 762 patient‐years per trial) were eligible for inclusion. DPP‐4 inhibitors were compared with placebo (five trials), active comparator (three trials), and standard care (two trials). Overall, treatment with DPP‐4 inhibitors was associated with a greater decline in eGFR than treatment with the comparators (weighted mean difference −1.12 mL/min/1.73m 2 , 95% confidence interval [CI] −1.61, −0.62; high‐certainty evidence). There were no detectable effects of DPP‐4 inhibitors on rates of doubling serum creatinine (risk ratio [RR] 1.10, 95% CI 0.90, 1.34; high‐certainty evidence), end‐stage kidney disease (RR 0.97, 95% CI 0.77, 1.23; high‐certainty evidence), death from kidney causes (RR 1.81, 95% CI 0.67, 4.93; low‐certainty evidence), or all‐cause mortality (RR 1.01, 95% CI 0.95, 1.09; high‐certainty evidence). DPP‐4 inhibitors significantly reduced the risks of the surrogate kidney outcome of new albuminuria (RR 0.88, 95% CI 0.8, 0.98; moderate‐certainty evidence) and worsening albuminuria (RR 0.88, 95% CI 0.82, 0.94; moderate‐certainty evidence). There was no difference in the safety outcome of acute kidney injury (RR 1.04, 95% CI 0.57, 1.87; high‐certainty evidence). Conclusions Dipeptidyl peptidase‐4 inhibitors are associated with a greater decline in eGFR, despite reducing the development and progression of albuminuria, and have no clear effect on other key kidney outcomes.