Pleiotropic effects of antidiabetic agents on renal and cardiovascular outcomes: a meta-analysis of randomized controlled trials

Background: This meta-analysis was conducted to examine the pleiotropic effects of all available antidiabetic agents except insulin for type 2 diabetes on renal and cardiovascular outcomes.

Methods: A systematic literature search was performed in PubMed, EMBASE, and Cochrane database to identify randomized-controlled trials which compared the effectiveness between all antidiabetic agents apart from insulin regarding all aspects of renal and cardiovascular outcomes. Random effect model was utilized to compute for hazard ratio.

Results: Nineteen articles with 140,851 participants were included in this meta-analysis. When compared with placebo, SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors exhibited significantly lower hazard ratios of progression of albuminuria. SGLT-2 inhibitors and DPP-4 inhibitors showed a significantly higher hazard ratio of regression of albuminuria. Only SGLT-2 inhibitors illustrated significantly lower hazard ratios of doubling of serum creatinine and incidence of renal replacement therapy (RRT). A significantly lower hazard ratio of composite renal outcome was detected in both SGLT-2 inhibitors and GLP-1 agonists. A significantly lower hazard ratio of all-cause mortality was identified in SGLT-2 inhibitors and GLP-1 agonist. Furthermore, a significantly lower hazard ratio of cardiovascular mortality was found in both SGLT-2 inhibitors and GLP-1 agonists.

Conclusion: Comparing across all antidiabetic agents apart from insulin, SGLT-2 inhibitors provided extensively renoprotective effects among diabetic patients as well as reduced hazard ratios of heart failure, cardiovascular mortality, and all-cause mortality. GLP-1 agonists yielded benefits regarding progression of albuminuria, composite renal outcome, and cardiovascular and all-cause mortalities. DPP-4 inhibitors offered only renal protection including progression and regression of albuminuria.