Cardiovascular and Renal Outcomes with SGLT-2 Inhibitors versus GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Mellitus and Chronic Kidney Disease: A Systematic Review and Network Meta-analysis

Abstract

BackgroundEmerging evidence suggests that sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are associated with decreased risk of cardiovascular and renal events in type 2 diabetes mellitus (DM) patients. However, no study to date has compared the effect of SGLT-2 inhibitors with that of GLP-1 RAs in type 2 DM patients with chronic kidney disease (CKD). We herein investigated the benefits of SGLT-2 inhibitors and GLP-1 RAs in CKD patients.MethodsWe performed a systematic literature search through October 2020. We selected randomized control trials that compared the risk of major adverse cardiovascular events (MACE) and a composite of renal outcomes. We performed a network meta-analysis to compare SGLT-2 inhibitors with GLP-1 RA indirectly. Risk ratios (RRs) with corresponding 95% confidence interval (CI) were synthesized.ResultsThirteen studies were selected with a total of 24,887 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95 %CI]; 0.86 [0.74-0.99] and 0.68 [0.62-0.75], respectively). However, GLP-1 RAs did not reduce cardiovascular and renal risk (RR 0.91 [0.79-1.05] and 0.91 [0.81-1.02], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.9 [0.75-1.08]), while SGLT-2 inhibitors were associated with. a lower risk of renal events compared to GLP-1 RAs (RR 0.75 [0.64-0.87]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE than placebo (RR 0.81 [0.68-0.97]), while exendin-4 analogues did not (RR 1.03 [0.86-1.23]).ConclusionsIn patients with type 2 DM and CKD, SGLT-2 inhibitors were associated with a decreased risk of cardiovascular and renal events, but GLP-1 RAs were not. SGLT-2 inhibitors significantly decreased the risk of renal events compared to GLP-1 RAs. Among GLP-1 RAs, GLP-1 analogues showed a positive impact, while exendin-4 analogues did not.

In Reply to ‘Glucagon-like Peptide-1 Receptor Agonists and the Risk of Acute Kidney Injury: Alarming, or Not?’

“…5 In 2 very recent metaanalyses, SGLT2 inhibitors were shown to have a lower risk of AKI than both GLP-1 RAs and placebo, and they were associated with a marked decrease in both cardiovascular and kidney events-benefits not seen with GLP-1 RAs. 6,7 In our opinion, SGLT2 inhibitors are preferable to GLP-1 RAs in most patients with CKD and can be used in patients with or without diabetes.…”