March 29, 2025
3 min learn
Key takeaways:
- Oral semaglutide lowered danger for cardiovascular occasions in individuals with sort 2 diabetes, atherosclerotic CVD and kidney illness.
- It’s now the primary and solely oral GLP-1 receptor agonist with confirmed CV profit.
CHICAGO — Oral semaglutide lowered danger for main antagonistic CV occasions by 14% in high-risk adults with sort 2 diabetes no matter SGLT2 inhibitor use, in response to information introduced on the American Faculty of Cardiology Scientific Session.
Researchers presenting findings from the SOUL trial, concurrently revealed in The New England Journal of Medication, additionally discovered that the general security profile of oral semaglutide 14 mg (Rybelsus, Novo Nordisk), a GLP-1 receptor agonist accredited for individuals with sort 2 diabetes, was just like what has been noticed in earlier semaglutide trials, including to the favorable risk-benefit profile for the category and making this the primary oral GLP-1 to indicate CV profit.
Oral semaglutide lowered danger for cardiovascular occasions in individuals with sort 2 diabetes, atherosclerotic CVD and kidney illness. Picture: Adobe Inventory
“The examine design for SOUL was not terribly totally different from the opposite CV outcomes trials which have targeted on high-risk ASCVD sufferers; nevertheless, we amplified it with prevalent, identified ASCVD, making it a real secondary prevention inhabitants, whereas additionally including to it a power kidney illness cohort,” Healio | Cardiology As we speak Editorial Board Member Darren Okay. McGuire, MD, MHSc, professor of drugs within the division of cardiology, Dallas Coronary heart Ball Chair for Analysis on Coronary heart Illness in Ladies and Distinguished Educating Professor on the College of Texas Southwestern Medical Middle, stated throughout an interview. “We hit the goal we had been anticipating. These findings carry us again to heart and help the truth that oral semaglutide will generate the identical CV advantages as the remainder of the category of GLP-1 receptor agonists.”
SOUL was a double-blind, event-driven, superiority trial together with 9,650 adults aged 50 years or older with longstanding sort 2 diabetes, recognized ASCVD, CKD or each, adopted for a imply of 49.5 months. Researchers randomly assigned sufferers to obtain oral semaglutide steadily titrated to the maximal, 14-mg dose or placebo on high of normal care. Regardless of some having CKD, kidney operate was well-preserved on this cohort, with a imply estimated glomerular filtration charge of 74 mL/min/1.73 m2; greater than half of contributors had been additionally taking SGLT2 inhibitors sooner or later in the course of the trial.
The first end result was a composite of CV loss of life, nonfatal MI or nonfatal stroke; confirmatory secondary outcomes included main renal occasions.
At follow-up, 12% of contributors within the semaglutide group (incidence charge, 3.1 occasions per 100 person-years) and 13.8% of contributors within the placebo group (incidence charge, 3.7 occasions per 100 person-years) skilled a main end result occasion, for an HR of 0.86 (95% CI, 0.77-0.96; P = .0006).
Darren Okay. McGuire
“Importantly, at 3 years that was an absolute distinction of two%, yielding a quantity wanted to deal with of fifty,” McGuire stated in the course of the presentation.
The primary confirmatory secondary end result — a kidney-related composite of CV loss of life, kidney loss of life, persistent eGFR discount of at the least 50%, persistent eGFR of lower than 15 mL/min/1.73 m2 and power kidney alternative remedy — didn’t differ between teams.
Due to that, the opposite two confirmatory secondary outcomes — CV loss of life (HR = 0.93; 95% CI, 0.8-1.09) and main antagonistic limb occasions (HR = 0.71; 95% CI, 0.52-0.96) — weren’t examined for significance, McGuire stated.
Severe antagonistic occasions didn’t differ between the teams.
In a prespecified evaluation concurrently revealed in Circulation, researchers discovered the SOUL outcomes remained constant no matter background SGLT2 remedy (P for interplay = .66), suggesting an impartial remedy profit with oral semaglutide, McGuire stated.
“Supply of this pill is extra sophisticated than ordinary,” McGuire advised Healio. “Due to the mechanism of its supply, oral semaglutide should follow the gastric mucosa. It should be taken in a fasting state with minimal liquid consumption — 4 oz of water after which nothing else orally whereas the pill is delivering the medication. We weren’t certain if a big inhabitants may comply with these guidelines. What this examine reveals is, on common, individuals received the medication. That makes these information very generalizable and prescribable.”
Reference:
For extra data:
Darren Okay. McGuire, MD, MHSc, might be reached at darren.mcguire@utsouthwestern.edu.
Perspective
Again to High
Knowledge from SOUL are additional testomony to the advantages of GLP-1s, notably semaglutide, in sufferers with CV danger, specifically these with diabetes and renal illness. This examine demonstrated an essential discount in a mixed three-point MACE endpoint of cardiac loss of life, nonfatal MI and stroke. I’m not stunned with the extent of influence. The authors did a very good job explaining why their first hierarchical variable — renal illness — didn’t meet statistical significance. These sufferers, regardless of having kidney illness, had a eGFR within the regular vary, versus contributors from the FLOW trial, which enrolled fewer sufferers who additionally had worse renal operate and a a lot decrease eGFR. We all know that sicker individuals typically derive higher advantages with an intervention, and that is one thing that has plagued main prevention trials for years. Nonetheless, if one seems to be on the information for nonfatal MI, there may be not a affected person on the market that may not like to forestall that sort of occasion. That is additionally what we would have anticipated contemplating what we all know concerning the bioavailability of oral semaglutide vs. the injectable model.
Does this examine damper my enthusiasm for GLP-1s, or for semaglutide particularly? The reply is not any. The SUSTAIN and SELECT research drove a number of my medical exercise and the best way I deal with sufferers as a heart specialist. If there’s a affected person who suits the phenotype of this examine and so they simply won’t take an injectable model of this drug, I might don’t have any hesitation prescribing the oral treatment.
There may be nonetheless work to do. We should be certain this data is disseminated to physicians of all specialties, specifically main care physicians, nephrologists and cardiologists. We should be certain they perceive the information in addition to the constraints.
Howard Weintraub, MD
Scientific Director
Middle for the Prevention of Cardiovascular Illness
NYU Langone Coronary heart
Scientific Professor
Division of Medication
Leon H. Charney Division of Cardiology
NYU Grossman Faculty of Medication
Disclosures: Weintraub studies receiving guide charges from Novo Nordisk and serving as a medical investigator for the SELECT trial.
Sources/Disclosures
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McGuire DK, et al. Joint American Faculty of Cardiology/Journal of the American Coronary heart Affiliation late-breaking medical trials III. Introduced at: American Faculty of Cardiology Scientific Session; March 29-31, 2025; Chicago (hybrid assembly).
Disclosures:
McGuire studies receiving guide charges from Altimmune, Alveus Pharma, Amgen, Utilized Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, CSL Behring, Eli Lilly, Esperion, Intercept Prescribed drugs, Kailera, Lexicon, Metsera, Neurotronics, NewAmsterdam, Novo Nordisk, Pfizer and Ventyx Prescribed drugs.
