Semaglutide and tirzepatide are associated with weight, but within two years they received four further indications. The US FDA added heart protection, kidney protection, treatment of sleep apnoea and treatment of fatty liver inflammation to their labels. Each of these decisions rests on a large placebo-controlled trial. Below you will find the numbers from these trials, the dates of the agency's decisions and a pointer on which molecule to choose when more than kilograms counts.
Which benefits beyond weight have trials confirmed?
Trials have confirmed benefits for four organs: the heart, the kidneys, the airways during sleep and the liver. Semaglutide has the most such data today. Tirzepatide is catching up in trials on heart failure, sleep apnoea and the liver. The table collects all results in one place.
| Organ | Molecule and weekly dose | Trial | Result against placebo | Status |
|---|---|---|---|---|
| Heart | semaglutide 2.4 mg | SELECT, 17,604 people | heart attack, stroke or cardiac death: 6.5 against 8.0 percent | US indication since 8 March 2024 |
| Heart | tirzepatide up to 15 mg | SUMMIT, 731 people | cardiac death or worsening heart failure: 9.9 against 15.3 percent | phase 3 trial result |
| Kidneys | semaglutide 1 mg | FLOW, 3,533 people | risk of major kidney events 24 percent lower | US indication since 28 January 2025 |
| Sleep | tirzepatide 10 or 15 mg | SURMOUNT-OSA, two trials | 25 to 29 fewer apnoeas per hour against about 5 | US indication since 20 December 2024 |
| Liver | semaglutide 2.4 mg | ESSENCE, 800 people analysed | resolution of inflammation: 62.9 against 34.3 percent | US indication since 15 August 2025 |
| Liver | tirzepatide 5, 10 or 15 mg | SYNERGY-NASH, 190 people | resolution of inflammation: 44 to 62 against 10 percent | phase 2 trial result |
All of these trials lasted at least a year. In each of them the effect was compared with placebo given in the same way.
What did the SELECT trial show about the heart?
The SELECT trial showed that semaglutide lowers the risk of heart attack, stroke and cardiac death by 20 percent. It included 17,604 people aged at least 45. Each of them already had heart or vascular disease. All were overweight or obese, but none had diabetes. Half received semaglutide at 2.4 mg once a week, half received placebo.
Follow-up lasted 39.8 months on average. A heart attack, stroke or cardiac death occurred in 569 of 8,803 people in the semaglutide group, or 6.5 percent. In the placebo group such an event affected 701 of 8,801 people, or 8.0 percent. The results were published in the New England Journal of Medicine in 2023. On this basis the FDA added an indication to reduce the risk of cardiovascular events to Wegovy on 8 March 2024.
It was the first such indication for an obesity drug. Before that, heart protection had been proven for semaglutide only in people with type 2 diabetes.
Does tirzepatide also protect the heart?
Tirzepatide has its own heart trial, SUMMIT, devoted to heart failure with preserved ejection fraction. This is a form of heart failure in which the heart contracts normally but relaxes poorly. Obesity clearly raises the risk of developing it. The trial included 731 people with this condition and a body mass index of at least 30.
Half of the participants received tirzepatide at up to 15 mg a week, half placebo. Median follow-up was 104 weeks. Cardiac death or worsening heart failure occurred in 9.9 percent of people on tirzepatide and 15.3 percent on placebo. The number of worsening events alone fell from 14.2 to 8.0 percent.
There were too few cardiac deaths in both groups to draw conclusions: 8 against 5 cases. The whole difference therefore came from worsening events that needed treatment. After a year the Kansas City quality of life questionnaire score improved by 19.5 points on tirzepatide and by 12.7 points on placebo. The paper was published in the New England Journal of Medicine in 2025.
What does semaglutide do for the kidneys?
Semaglutide slows the loss of kidney function in people with type 2 diabetes and chronic kidney disease. This was shown by the FLOW trial of 3,533 people. Participants received semaglutide at 1 mg a week or placebo. The monitoring committee recommended stopping the trial early after an interim analysis, because the difference was already clear.
Median follow-up was 3.4 years. A major kidney event or cardiac death affected 331 people in the semaglutide group and 410 in the placebo group. The risk was thus 24 percent lower. The risk of cardiac death fell by 29 percent, and the risk of death from any cause by 20 percent. Kidney filtration declined more slowly by 1.16 ml per minute each year.
The FDA added this indication to Ozempic on 28 January 2025. It covers reducing the risk of worsening kidney disease, kidney failure and cardiac death.
How does tirzepatide affect sleep apnoea?
Tirzepatide reduces the number of breathing pauses during sleep and is the first drug approved in the US to treat this condition. Obstructive sleep apnoea means that the airways collapse during sleep. Breathing stops or becomes shallow, often dozens of times an hour. Excess body fat is one of the main causes.
SURMOUNT-OSA consists of two phase 3 trials run over 52 weeks. In the first, participants did not use a CPAP machine, a mask that delivers air under pressure. In the second, they used it throughout. At the start the average number of apnoeas and hypopnoeas was 51.5 and 49.5 per hour of sleep. The average body mass index exceeded 38.
| Trial | Change in apnoeas per hour, tirzepatide | Change, placebo | Difference |
|---|---|---|---|
| Without CPAP | minus 25.3 | minus 5.3 | minus 20.0 |
| With CPAP | minus 29.3 | minus 5.5 | minus 23.8 |
In both trials systolic blood pressure, CRP protein levels and the participants' own rating of sleep also improved. The FDA approved tirzepatide as Zepbound for moderate and severe sleep apnoea in adults with obesity on 20 December 2024. The label gives maintenance doses of 10 mg or 15 mg once a week for this indication.
What happens to the liver?
Both molecules reverse fatty liver inflammation in trials with biopsy. The disease is abbreviated MASH and develops when fat building up in the liver triggers inflammation. Over time the inflammation leads to fibrosis, that is scarring of the organ. Assessment requires a tissue sample, so these trials are among the most demanding.
The ESSENCE trial included 1,197 people with fibrosis of stage 2 or 3. The first analysis was carried out after 72 weeks in 800 of them. Inflammation resolved without worsening fibrosis in 62.9 percent of people on semaglutide and 34.3 percent on placebo. Fibrosis improved in 36.8 against 22.4 percent. Body weight fell by 10.5 percent on average against 2.0 percent. The trial will last 240 weeks in total.
On this basis the FDA approved Wegovy for the treatment of MASH on 15 August 2025. It was an accelerated approval, that is one based on biopsy results, with the condition that further data confirm the clinical benefit.
Tirzepatide has so far completed a phase 2 trial, SYNERGY-NASH, lasting 52 weeks. Inflammation resolved in 44 percent of people on 5 mg, 56 percent on 10 mg and 62 percent on 15 mg. In the placebo group it resolved in 10 percent. An improvement in fibrosis of at least one stage was seen in 51 to 55 percent of those treated and 30 percent on placebo. A similar direction for retatrutide, a fall in liver fat, is described in the guide on retatrutide phase 3 trials.
Semaglutide or tirzepatide, when more than weight counts?
The choice depends on the organ you care about, because each molecule has different strengths in the data. Semaglutide has hard results for the heart, kidneys and liver, confirmed by approvals. Tirzepatide leads in sleep apnoea and in heart failure with preserved ejection fraction. In a direct weight comparison tirzepatide came out ahead, as the guide semaglutide vs tirzepatide vs retatrutide explains.
| Goal | Molecule with the strongest data | In the shop | Price |
|---|---|---|---|
| Heart after a heart attack or stroke | semaglutide | Semaglutide 3 mg Bio-Peptide | 90 EUR |
| Kidneys | semaglutide | Semaglutide 3 mg Bio-Peptide | 90 EUR |
| Sleep apnoea | tirzepatide | Tirzepatide 20 mg Bio-Peptide | 200 EUR |
| Heart failure with obesity | tirzepatide | Tirzepatide 40 mg Quick Pen Nouveaux | 350 EUR |
| Liver | semaglutide, tirzepatide | both molecules | from 90 EUR |
All brands and variants are collected on the molecule pages: semaglutide and tirzepatide. The mechanism behind these results is described in the guide on GLP-1 and incretins. How many weeks one vial lasts on the label schedules is calculated in a separate guide on how long a GLP-1 vial lasts.
Where do these data end?
The trials described were run with the approved drugs Wegovy, Ozempic and Zepbound, under medical supervision. Semaglutide and tirzepatide in our shop are material for laboratory research. The same molecule does not carry over the trial results or the drug approval. The difference between a drug and research material is explained in the guide why semaglutide and tirzepatide are prescription only.
The same papers also counted the people who stopped treatment. In SELECT, 16.6 percent of people on semaglutide and 8.2 percent on placebo stopped because of side effects. In SUMMIT the figures were 6.3 against 1.4 percent. Most often these were gastrointestinal complaints. The legal status of these substances is described in the guide on the legal status of peptides.
Frequently asked questions
Does semaglutide protect the heart in people without diabetes?
Yes. The SELECT trial included only people without diabetes and showed a 20 percent lower risk of heart attack, stroke and cardiac death.
Which drug is approved for sleep apnoea?
Tirzepatide as Zepbound, by FDA decision of 20 December 2024, in adults with obesity and moderate or severe sleep apnoea.
Does semaglutide help the kidneys?
In the FLOW trial in people with type 2 diabetes and kidney disease the risk of major kidney events was 24 percent lower.
Do GLP-1 drugs treat fatty liver?
Semaglutide has had accelerated FDA approval for MASH since 15 August 2025. Tirzepatide gave similar results in a phase 2 trial.
Which peptide to choose when the heart matters?
After a heart attack or stroke semaglutide has the strongest data. In heart failure with preserved ejection fraction and obesity tirzepatide was studied.
This is information about published research, not medical advice. The choice of treatment belongs to a doctor.
Sources
- Lincoff AM, Brown-Frandsen K, Colhoun HM et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine, 2023, 389(24): 2221-2232. https://doi.org/10.1056/NEJMoa2307563
- FDA. FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or Overweight, 8 March 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-treatment-reduce-risk-serious-heart-problems-specifically-adults-obesity-or
- Packer M, Zile MR, Kramer CM et al. Tirzepatide for Heart Failure with Preserved Ejection Fraction and Obesity. New England Journal of Medicine, 2025, 392(5): 427-437. https://doi.org/10.1056/NEJMoa2410027
- Perkovic V, Tuttle KR, Rossing P et al. Effects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes. New England Journal of Medicine, 2024, 391(2): 109-121. https://doi.org/10.1056/NEJMoa2403347
- Novo Nordisk. FDA approves Ozempic (semaglutide) as the only GLP-1 RA to reduce the risk of worsening kidney disease and cardiovascular death in adults with type 2 diabetes and chronic kidney disease, 28 January 2025. https://www.prnewswire.com/news-releases/fda-approves-ozempic-semaglutide-as-the-only-glp-1-ra-to-reduce-the-risk-of-worsening-kidney-disease-and-cardiovascular-death-in-adults-with-type-2-diabetes-and-chronic-kidney-disease-302362466.html
- Malhotra A, Grunstein RR, Fietze I et al. Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. New England Journal of Medicine, 2024, 391(13): 1193-1205. https://doi.org/10.1056/NEJMoa2404881
- FDA. FDA Approves First Medication for Obstructive Sleep Apnea, 20 December 2024. https://www.fda.gov/news-events/press-announcements/fda-approves-first-medication-obstructive-sleep-apnea
- FDA. Zepbound (tirzepatide) injection, prescribing information, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/217806s013lbl.pdf
- Sanyal AJ, Newsome PN, Kliers I et al. Phase 3 Trial of Semaglutide in Metabolic Dysfunction-Associated Steatohepatitis. New England Journal of Medicine, 2025, 392(21): 2089-2099. https://doi.org/10.1056/NEJMoa2413258
- FDA. FDA Approves Treatment for Serious Liver Disease Known as MASH, 15 August 2025. https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-treatment-serious-liver-disease-known-mash
- Loomba R, Hartman ML, Lawitz EJ et al. Tirzepatide for Metabolic Dysfunction-Associated Steatohepatitis with Liver Fibrosis. New England Journal of Medicine, 2024, 391(4): 299-310. https://doi.org/10.1056/NEJMoa2401943