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Oral Semaglutide and Cardiovascular Outcomes in Persons With Type 2 Diabetes, According to SGLT2i Use: Prespecified Analyses of the SOUL Randomized Trial
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John E. Deanfield,
Johannes F.E. Mann,
Rosario Arechavaleta,
Steve Bain ,
Harpreet S. Bajaj ,
Katrine Bayer Tanggaard,
Andreas L. Birkenfeld ,
John B. Buse ,
Zaklina Davicevic-Elez,
Cyrus Desouza ,
Scott S. Emerson,
Mads D.M. Engelmann,
G. Kees Hovingh,
Silvio E. Inzucchi ,
Pardeep S. Jhund ,
Sharon L. Mulvagh ,
Rodica Pop-Busui ,
Neil R. Poulter ,
Søren Rasmussen,
Shih-Te Tu,
Darren K. McGuire
Circulation, Volume: 151, Issue: 23, Pages: 1639 - 1650
Swansea University Author:
Steve Bain
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PDF | Version of Record
© 2025 The Authors. Circulation is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial-NoDerivs License.
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DOI (Published version): 10.1161/circulationaha.125.074545
Abstract
Background: Both glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) improve cardiovascular (CV) outcomes in people with type 2 diabetes (T2D) and CV or chronic kidney disease (CKD). However, there are limited data about the effect of combinin...
| Published in: | Circulation |
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| ISSN: | 0009-7322 1524-4539 |
| Published: |
Wolters Kluwer Health, Inc.
2025
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| Online Access: |
Check full text
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa69195 |
| Abstract: |
Background: Both glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter-2 inhibitors (SGLT2i) improve cardiovascular (CV) outcomes in people with type 2 diabetes (T2D) and CV or chronic kidney disease (CKD). However, there are limited data about the effect of combining these agents on CV and safety outcomes.Methods: The SOUL trial (NCT03914326) randomised 9650 participants with T2D and atherosclerotic CV disease and/or CKD to oral semaglutide or placebo. As prespecified, participants were analysed according to baseline use of SGLT2i (Yes: n=2596, No: n=7054) and, subsequently for any use of SGLT2i during the trial (Yes: n=4718, No: n=4932). The primary outcome was time to first major adverse cardiovascular event (MACE), defined as cardiovascular death, non-fatal myocardial infarction or non-fatal stroke. Safety was evaluated by comparing the incidence of serious adverse events.Results: Over a mean follow-up of 47.5±10.9 months, the risk of the primary outcome in the overall trial population was 14% lower for oral semaglutide vs placebo (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.77; 0.96). In those taking SGLT2i at baseline, there were 143/1296 (semaglutide) versus 158/1300 (placebo) primary outcome events (HR 0.89; 95% CI 0.71; 1.11); and 436/3529 versus 510/3525, respectively, in participants not taking SGLT2i at baseline (HR 0.84; 95% CI 0.74; 0.95; P-interaction 0.66). An analysis of MACE by any in-trial SGLT2i use versus no use also showed no evidence of heterogeneity in the effects of oral semaglutide. The adverse event profiles of oral semaglutide with or without concomitant SGLT2i were similar.Conclusions: Oral semaglutide reduced MACE outcomes independently of concomitant SGLT2i treatment and this combination appeared to be safe. |
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| Keywords: |
cardiovascular diseases; cardiovascular system; diabetes mellitus, type 2; glucagon-like peptide-1 receptor agonists; renal insufficiency, chronic; semaglutide; sodium-glucose transporter 2 inhibitors |
| College: |
Faculty of Medicine, Health and Life Sciences |
| Funders: |
The SOUL trial was funded by Novo Nordisk A/S. |
| Issue: |
23 |
| Start Page: |
1639 |
| End Page: |
1650 |