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. 2021 Jan 7;20(1):14.
doi: 10.1186/s12933-020-01197-z.

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  1   2 , Mako Wakabayashi  3 , Abhinav Bhalla  1 , Nitin Chopra  1 , Hirotaka Miyashita  1 , Takahisa Mikami  4 , Hiroki Ueyama  1 , Tomohiro Fujisaki  5 , Yusuke Saigusa  6 , Takahiro Yamaji  2 , Kengo Azushima  2 , Shingo Urate  2 , Toru Suzuki  2 , Eriko Abe  2 , Hiromichi Wakui  7 , Kouichi Tamura  2
Affiliations

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 et al. Cardiovasc Diabetol. .

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.

Keywords: Cardiovascular disease; Chronic kidney disease; Diabetes mellitus; GLP-1 receptor agonist; Meta-analysis; Renal outcomes; SGLT2 inhibitors.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow diagram for study selection
Fig. 2
Fig. 2
Quality assessment (Cochrane risk of bias tool) for included RCTs. RCT randomized control study
Fig. 3
Fig. 3
Network plot for MACE. SGLT-2 sodium-glucose cotransporter 2, GLP-1 RA glucagon-like peptide-1 receptor agonist, MACE major adverse cardiovascular events
Fig. 4
Fig. 4
Network meta-analysis reporting risk ratio (RR) for MACE in CKD patients. SGLT-2 sodium-glucose cotransporter 2, GLP-1 RA glucagon-like peptide-1 receptor agonist, MACE major adverse cardiovascular events, CKD chronic kidney disease
Fig. 5
Fig. 5
Network meta-analysis reporting risk ratio (RR) for renal outcomes in CKD patients. SGLT-2 sodium-glucose cotransporter 2, GLP-1 RA glucagon-like peptide-1 receptor agonist, CKD chronic kidney disease
See this image and copyright information in PMC

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