Separate and combined effects of empagliflozin and semaglutide on vascular function: A 32‐week randomized trial
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Aim: Despite the increasing use of combination treatment with sodium‐glucose cotransporter 2 inhibitors and glucagon‐like peptide‐1 receptor agonists, data are limited on the effects of combination treatment on markers of cardiovascular disease. This study aimed to investigate the effect of empagliflozin, semaglutide, and their combination on vascular function. Materials and Methods: In total, 120 patients with type 2 diabetes were randomized into four groups (n = 30 in each) for 32 weeks: placebo, semaglutide, empagliflozin, and their combination. The study had two co‐primary outcomes: change in arterial stiffness and kidney oxygenation. This paper reports on arterial stiffness assessed as carotid‐femoral pulse wave velocity. Secondary outcomes included 24‐h blood pressure (BP), 24‐h central BP, urinary albumin to creatinine ratio and glycaemic control assessed by both continuous glucose monitoring and glycated haemoglobin. Results: The carotid‐femoral pulse wave velocity did not change significantly in any of the groups compared with placebo. Twenty‐four‐hour systolic BP was reduced by 10 mmHg (95% CI 6–14), p < .001 in the combination group, significantly superior to both placebo and monotherapy ( p < .05). Combination treatment increased glycaemic time in range from 72% at baseline to 91% at week 32, p < .001, without increasing time below range. The urinary albumin to creatinine ratio decreased by 36% (95% CI 4–57), p = .03 in the combination group compared with placebo. Conclusions: Empagliflozin, semaglutide, or their combination did not reduce arterial stiffness. Combination treatment showed a substantial and clinically important reduction in 24‐h systolic BP compared with either treatment alone. Combination treatment increased glycaemic time in range without increasing the risk of hypoglycaemia.
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Several smaller short-term trials reported additive effects of GLP-1 receptor agonists and SGLT2 inhibitors on surrogate outcomes such as body weight, blood pressure and HbA1c.
“Several smaller short-term trials reported additive effects of GLP-1 RAs and SGLT2i on surrogate outcomes such as body weight, blood pressure and HbA1c18–21.”
From Effects of semaglutide with and without concomitant SGLT2 inhibitor use in participants with type 2 diabetes and chronic kidney disease in the FLOW trial (2024) · cites this paper as [19]
The Introduction reports an additive systolic blood-pressure reduction in the DURATION-8 trial, and §4 (Discussion) describes additive weight reduction. But the Discussion says most previous combination trials found effects less than additive, while §3.3.1 found no HbA1c difference between combination treatment and semaglutide alone. The source therefore does not support the broad claim that several trials reported additive effects across all three outcomes. Page numbers are unavailable in our copy. (LLM, conf=0.88)
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Mann, J. F. E., Rossing, P., Bakris, G., Belmar, N., Bosch-Traberg, H., Busch, R., Charytan, D. M., Hadjadj, S., Gillard, P., Górriz, J. L., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03133-0 · Cited by 200 · see citing works
- Authors
- Vernstrøm, L., Gullaksen, S., Sørensen, S. S., Funck, K. L., Laugesen, E., & Poulsen, P. L.
- Affiliations
- Aarhus University (DK)
- Aarhus University Hospital (DK)
- Corresponding author
- Vernstrøm, Liv
- Venue
- Diabetes, Obesity and Metabolism
- Publisher
- Wiley
- Published
- 2024-01-19
- Volume
- 26
- Issue
- 5
- Pages
- 1624-1635
- ISSN
- 1462-8902 (ISSN-L)
- 1463-1326
- OpenAlex
- W4391031343
- Cited by
- 30
- References
- 14
- Citations by year
- 2026: 11 · 2025: 12 · 2024: 7
- FWCI
- 9.81
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetes Obesity and Metabolism (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Funders
- Lægeforeningen (2019‐3780/41)
- Novo Nordisk Fonden (NNF170C0029064)
- Sundhedsvidenskabelige Fakultet, Aarhus Universitet
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- empagliflozin, semaglutide, combination therapy, type 2 diabetes, vascular function, arterial stiffness, pulse wave velocity, blood pressure, albumin-creatinine ratio, kidney oxygenation, SGLT2 inhibitors, GLP-1 receptor agonists, HbA1c
- MeSH terms
- Semaglutide, Albumins, Benzhydryl Compounds, Blood Glucose, Creatinine, Diabetes Mellitus, Type 2, Double-Blind Method, Glucagon-Like Peptides, Glucosides, Humans, Hypoglycemic Agents, Blood Glucose Self-Monitoring, Treatment Outcome, Pulse Wave Analysis
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