An analysis by an international team of researchers has concluded that taking oral semaglutide may reduce heart-related hospitalisations and deaths among those with a history of heart failure and type 2 diabetes.
Data from a trial funded by Novo Nordisk – which produces the glucagon-like peptide-1 (GLP-1) receptor agonist semaglutide for weight loss (Wegovy) and diabetes (Ozempic) – were recently re-analysed by a global team of researchers.
The double-blind study involved 9 650 participants across 33 countries recruited between 2019 and 2021 and followed for almost four years on average.
By the end of the study period, participants with a history of heart failure had 22% fewer adverse cardiovascular events while taking a daily pill of semaglutide than those in a placebo group. No heart health benefits were detected in people without pre-existing heart conditions.
“These data support the potential benefit of oral semaglutide in reducing heart failure events in people with type 2 diabetes and heart conditions,” Oregon Health & Science University diabetologist Rodica Pop-Busui and colleagues wrote in their paper.
“Limitations include those intrinsic to a secondary analysis, such as the small number of participants in some of the subgroups,” the team cautioned.
Still, their findings are backed by previous research, which has also suggested semaglutide can reduce cardiovascular events, including strokes and heart attacks, among certain patients by almost 20% over about three years, apparently regardless of weight loss.
However, animal studies warn that these benefits may come with more serious risks, in addition to common side effects like nausea and vomiting.
In 2024, a study in mice revealed that semaglutide can have a shrinking effect on a type of muscle specific to mammalian hearts. Other studies have also found significant skeletal muscle loss, along with the desired fat loss and anti-diabetic effects of this molecule.
Type 2 diabetes impacts roughly half a billion people globally, and heart failure is one of its most common complications. For people with these risk factors, semaglutide’s benefits may outweigh its risks with appropriate medical guidance.
Other options, though, like bariatric surgery, still perform better for blood sugar control than the use of this drug.
As the mechanism behind semaglutide’s impact on cardiovascular disease is not yet understood, researchers have called for caution when it comes to widespread prescription of this medication for purposes beyond weight loss and diabetes management.
This research was published in JAMA.
Study details
Oral semaglutide and heart failure outcomes in persons with type 2 diabetes: a secondary analysis of the SOUL Randomised Clinical Trial
Rodica Pop-Busui, Søren Rasmussen, John Deanfield et al.
Published in JAMA on 2 February 2026
Abstract
Importance
Heart failure (HF) is a common complication of type 2 diabetes (T2D). Oral semaglutide reduced the risk of major adverse cardiovascular (CV) events (MACE; comprising CV death, nonfatal myocardial infarction, or nonfatal stroke) in people with T2D in the SOUL trial, but the impact on HF outcomes in these participants is unknown.
Objective
To evaluate the effect of oral semaglutide on HF events, MACE, and safety among participants with or without HF at baseline.
Design, Setting, and Participants
This is a secondary analysis of the double-blind, placebo-controlled, event-driven, phase 3b SOUL randomised clinical trial, which was conducted at 444 centres in 33 countries. Participants were enrolled from June 17, 2019, to March 24, 2021, and had T2D and atherosclerotic CV disease and/or chronic kidney disease, stratified according to the presence or absence of HF history at baseline. Data were analysed from December 2024 to August 2025.
Intervention
Once-daily oral semaglutide or placebo in addition to standard of care.
Main Outcomes and Measures
Pre-specified composite HF outcome (time to first occurrence of HF hospitalization, urgent HF visit, or CV death).
Results
Overall, 9650 participants (median [IQR] age, 66.0 [61.0-72.0] years; 2790 [28.9%] female) were randomised, with a mean (SD) follow-up of 47.5 (10.9) months. Of these participants, 2229 (23.1%) had HF history (991 [10.3%] with preserved ejection fraction, 592 [6.1%] with reduced ejection fraction, and 646 [6.7%] with unknown subtype). For participants with HF at baseline, the hazard ratio (HR) for risk of the composite HF outcome with oral semaglutide vs placebo was 0.78 (95% CI, 0.63-0.96) and was 1.01 (95% CI, 0.84-1.20) in those without HF at baseline (P for interaction = .06). Among participants with HF, the HR was 0.59 (95% CI, 0.39-0.86) in those with preserved ejection fraction and 0.98 (95% CI, 0.70-1.38) in those with reduced ejection fraction. There was no heterogeneity in the risk reduction of MACE with oral semaglutide in participants with HF history (HR, 0.83; 95% CI, 0.68-1.01) or without HF history (HR, 0.86; 95% CI, 0.75-0.98) (P for interaction = .77). Serious adverse event occurrence among participants with HF was similar with oral semaglutide (594 [53.8%]) and placebo (642 [57.1%]).
Conclusions and Relevance
In this secondary analysis of the SOUL randomised clinical trial, among individuals with T2D, atherosclerotic CV disease, and/or chronic kidney disease, a reduction of HF events was observed with use of oral semaglutide compared with placebo in those with a history of HF, without increasing the risk of serious adverse events. These data support the potential benefit of oral semaglutide in reducing HF events in people with T2D and HF.
See more from MedicalBrief archives:
Wegovy slashes heart risk by 57% – STEER study
Weight loss drug approved for heart disease prevention