Key result
SGLT-2 inhibitors and GLP-1 receptor agonists similarly reduced the risk of major adverse cardiovascular events compared to placebo, while SGLT-2 inhibitors were superior to GLP-1 receptor agonists in reducing hospitalization for heart failure and renal events.
Why the study?
GLP-1 receptor agonists and SGLT-2 inhibitors reduce cardiorenal outcomes, but direct head-to-head comparisons among GLP-1 RAs, SGLT-2 inhibitors, and DPP-4 inhibitors were lacking.
Do GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors reduce cardiorenal outcomes in adult patients with or without type 2 diabetes?
Meta-Analysis (n=181,143)
Yes
Do GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors reduce cardiorenal outcomes in adult patients with or without type 2 diabetes?
In a network meta-analysis of 23 CVOTs, SGLT-2 inhibitors and GLP-1 receptor agonists were superior to DPP-4 inhibitors for reducing MACE, with SGLT-2 inhibitors providing the greatest reduction in heart failure hospitalizations and renal events.
Answers are grounded in this paper and cite their sources.
Supports SGLT-2 inhibitors over GLP-1 agonists for heart failure and renal protection; confirms comparable MACE reduction versus placebo in diabetes.
Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium glucose co-transporter-2 (SGLT-2) inhibitors reduce cardiorenal outcomes. We performed a network meta-analysis to compare the effect on cardiorenal outcomes among GLP-1 RAs, SGLT-2 inhibitors and dipeptidyl peptidase-4 (DPP-4) inhibitors. Methods: We searched the PUBMED, Embase and Cochrane databases for relevant studies published up until 10 December 2021. Cardiovascular and renal outcome trials reporting outcomes on GLP-1RA, SGLT-2 inhibitors and DPP-4 inhibitors in patients with or without type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE); other outcomes were cardiovascular and total death, nonfatal myocardial infarction (MI), nonfatal stroke, hospitalization for heart failure (HHF), and renal outcome. Results: Twenty-three trials enrolling a total number of 181,143 participants were included. DPP-4 inhibitors did not lower the risk of any cardiorenal outcome when compared with placebo and were associated with higher risks of MACE, HHF, and renal outcome when compared with the other two drug classes. SGLT-2 inhibitors significantly reduced cardiovascular (RR = 0.88) and total (RR = 0.87) death, as compared with DPP-4 inhibitors, while GLP-1 RA reduced total death only (RR = 0.87). The comparison between GLP-1RA and SGLT-2 inhibitors showed no difference in their risks of MACE, nonfatal MI, nonfatal stroke, CV and total death; SGLT-2 inhibitors were superior to GLP-1RA in reducing the risk of HHF and the renal outcome (24% and 22% lower risk, respectively). Only GLP-1RA reduced the risk of nonfatal stroke (RR = 0.84), as compared with placebo. There was no head-to-head trial directly comparing these antidiabetic drug classes. Conclusions: SGLT-2 inhibitors and GLP-1RA are superior to DPP-4 inhibitors in reducing the risk of most cardiorenal outcomes; SGLT-2 inhibitors are superior to GLP-1RA in reducing the risk of HHF and renal events; GLP-1RA only reduced the risk of nonfatal stroke. Both SGLT-2 inhibitors and GLP-1RA should be the preferred treatment for type 2 diabetes and cardiorenal diseases.
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Giugliano et al. (2022) conducted a meta-analysis in Type 2 diabetes mellitus and cardiorenal diseases (n=181,143). GLP-1 receptor agonists vs. SGLT-2 inhibitors was evaluated on Major adverse cardiovascular events (MACE) (RR 0.98, 95% CI 0.91-1.07). SGLT-2 inhibitors and GLP-1 receptor agonists similarly reduced the risk of major adverse cardiovascular events compared to placebo, while SGLT-2 inhibitors were superior to GLP-1 receptor agonists in reducing hospitalization for heart failure and renal events.
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