Cardiovascular Diabetology (Jan 2021)

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

  • Takayuki Yamada,
  • Mako Wakabayashi,
  • Abhinav Bhalla,
  • Nitin Chopra,
  • Hirotaka Miyashita,
  • Takahisa Mikami,
  • Hiroki Ueyama,
  • Tomohiro Fujisaki,
  • Yusuke Saigusa,
  • Takahiro Yamaji,
  • Kengo Azushima,
  • Shingo Urate,
  • Toru Suzuki,
  • Eriko Abe,
  • Hiromichi Wakui,
  • Kouichi Tamura

DOI
https://doi.org/10.1186/s12933-020-01197-z
Journal volume & issue
Vol. 20, no. 1
pp. 1 – 13

Abstract

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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.

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