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

Background Emerging 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. Methods We performed a systematic literature search through November 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 RAs indirectly. Risk ratios (RRs) with corresponding 95% confidence intervals (CI) were synthesized. Results Thirteen studies were selected with a total of 32,949 patients. SGLT-2 inhibitors led to a risk reduction in MACE and renal events (RR [95% CI]; 0.85 [0.75–0.96] and 0.68 [0.59–0.78], respectively). However, GLP-1 RAs did not reduce the risk of cardiovascular or renal adverse events (RR 0.91 [0.80–1.04] and 0.86 [0.72–1.03], respectively). Compared to GLP-1 RAs, SGLT-2 inhibitors did not demonstrate a significant difference in MACE (RR 0.94 [0.78–1.12]), while SGLT-2 inhibitors were associated with a lower risk of renal events compared to GLP-1 RAs (RR 0.79 [0.63–0.99]). A sensitivity analysis revealed that GLP-1 analogues significantly decreased MACE when compared to placebo treatment (RR 0.81 [0.69–0.95]), while exendin-4 analogues did not (RR 1.03 [0.88–1.20]). Conclusions In 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 on cardiovascular and renal outcomes, while exendin-4 analogues did not.

Renal hemodynamic effects differ between antidiabetic combination strategies: randomized controlled clinical trial comparing empagliflozin/linagliptin with metformin/insulin glargine

“…Previously, several meta-analyses showed beneficial effects of SGLT2 inhibition in type 2 diabetes over a spectrum of cardiovascular and renal risk [ 9 – 11 ].…”

Systematic review and meta-analysis for prevention of cardiovascular complications using GLP-1 receptor agonists and SGLT-2 inhibitors in obese diabetic patients

“…Recent meta-analyses have shown protective effects of GLP-1 RAs and SGLT-2 inhibitors against CVD in patients with T2DM 26 – 28 . However, no head-to-head trials have compared the use of these drugs for the prevention of MACE in patients with obesity and T2DM.…”

Projection of the health and economic impacts of Chronic kidney disease in the Chilean population

“…These findings show the importance of targeting the progression of CKD as one of the key variables when establishing the treatment’s goals. The evidence shows several options for effective treatments for the management of early stages of CKD to reduce progression of the disease such as the treatment with SGTL2 inhibitors for earlier stages of CKD [ 60 – 63 ] and the multidisciplinary pre-dialysis treatment for stages 4 and 5 [ 25 , 46 ], or conservative management for certain individuals with ESKD as an option instead of RRT [ 28 , 64 ]. These strategies need to be studied in future models with real world data to assess their implementation, cost-effectiveness and the impact on CKD in Chile.…”