FDA Approves Semaglutide to Cut Heart Risk in Obesity (2024)

Table of Contents

1. What the FDA Did
2. Who the New Use Covers
3. What the Trial Showed
4. The Reasons the FDA Gave
5. Safety Warnings on the Label
6. What the Approval Does Not Do
7. What Published Research Reports on Semaglutide and the Heart
8. Later Steps: Liver Disease, the Shortage and Compounding
9. Dates and Status as of 11 October 2026
10. Primary Documents
11. Key Research Papers
12. Connections

1. What the FDA Did

The FDA news release “FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or Overweight” is dated 8 March 2024. It states that the agency “approved a new indication for use” — a new approved use — for one semaglutide injection already sold for weight management.

The new indication is “to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and either obesity or overweight.” According to the release, the drug is to be used together with a reduced-calorie diet and increased physical activity.

The release states that the drug “received Priority Review designation for this indication.” The action was a decision on one drug’s label announced by press release; no Federal Register document was found for it (see section 9).

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2. Who the New Use Covers

The release limits the new use to adults who have both of the following:

• Cardiovascular disease. The FDA defines this in the release as “a group of diseases of the heart and blood vessels.” The site’s Cardiovascular Disease page covers the condition.
• Obesity or overweight. The release states that obesity or overweight affect approximately 70% of American adults and that both “increase the risk for premature death and a variety of health problems, including heart attack and stroke.” The site’s Obesity page covers the condition.

The release adds that the same injection was already approved “to reduce excess weight and maintain weight reduction long term in certain adults with obesity or overweight and certain children with obesity,” also alongside a reduced-calorie diet and increased physical activity. The 2024 approval added the heart-risk use to that existing weight-management use.

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3. What the Trial Showed

The release describes the study behind the new indication as “a multi-national, multi-center, placebo-controlled double-blind trial.” What it reports about the trial:

• Size: it “randomly assigned over 17,600 participants” to receive either semaglutide or placebo.
• Usual care for everyone: participants in both groups also received standard-of-care medical treatment, which the release gives as, for example, management of blood pressure and cholesterol, plus healthy lifestyle counseling on diet and physical activity.
• Result: major adverse cardiovascular events, which the release defines as cardiovascular death, heart attack and stroke, occurred in 6.5% of participants who received semaglutide compared with 8% of those who received placebo. The FDA states that semaglutide “significantly reduced” this risk.

The release does not name the trial or give its length. The published report of a trial matching this description is summarized in section 7.

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4. The Reasons the FDA Gave

The release quotes John Sharretts, M.D., at the time director of the Division of Diabetes, Lipid Disorders, and Obesity in the FDA’s Center for Drug Evaluation and Research (CDER). He described the drug as “now the first weight loss medication to also be approved to help prevent life-threatening cardiovascular events in adults with cardiovascular disease and either obesity or overweight.”

He continued: “This patient population has a higher risk of cardiovascular death, heart attack and stroke. Providing a treatment option that is proven to lower this cardiovascular risk is a major advance for public health.”

These are the agency’s stated reasons, reported here as the FDA gave them.

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5. Safety Warnings on the Label

The release lists the safety information on the drug’s prescribing information:

• Boxed warning. The label carries a boxed warning, the release says, “to inform health care professionals and patients about the risk of thyroid C-cell tumors.” Because of this risk, the label excludes people with a personal or family history of medullary thyroid carcinoma (a type of thyroid cancer) and people with a rare condition called Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
• Allergy. The label also excludes people with a history of a severe allergic reaction to semaglutide or to any of the other ingredients; the release states that patients are to stop the drug immediately and seek medical help if a severe allergic reaction is suspected.
• Other warnings. Inflammation of the pancreas (pancreatitis), gallbladder problems including gallstones, low blood sugar, acute kidney injury, hypersensitivity reactions, diabetic retinopathy (damage to the eye’s retina), increased heart rate, and suicidal behavior or thinking.
• Low blood sugar with other drugs. The release describes the risk of low blood sugar as a topic for patients to discuss with their health care provider when the drug is used with insulin or with a medicine that causes insulin secretion.
• Monitoring. According to the release, health care professionals are to monitor patients for kidney disease, diabetic retinopathy, and depression or suicidal behaviors or thoughts.
• No doubling up. Because the drug contains semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, the label states it is not for use in combination with other semaglutide-containing products or other GLP-1 receptor agonists.

The release gives the most common side effects as nausea, diarrhea, vomiting, constipation, abdominal (stomach) pain, headache, fatigue, indigestion, dizziness, abdominal distension, belching, low blood sugar in patients with diabetes, gas, and gastroesophageal reflux disease (heartburn).

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6. What the Approval Does Not Do

• It does not cover people without established cardiovascular disease. The indication is for “adults with cardiovascular disease and either obesity or overweight.” People with excess weight but no cardiovascular disease are covered only by the earlier weight-management use.
• It is not an approval of compounded semaglutide. The decision concerns one FDA-approved product; pharmacy-made copies were not part of it (section 8).
• It does not replace diet and activity. The approved use is in addition to a reduced-calorie diet and increased physical activity, and in the trial it was added on top of standard medical care.
• It does not remove the label’s warnings. The boxed warning and the other warnings in section 5 apply to the new use as well.
• It is not a rule. It is a decision on a single drug’s label, not a regulation that applies to other weight-loss medicines.

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7. What Published Research Reports on Semaglutide and the Heart

The FDA release cites no published studies and does not name its trial. The papers below, each checked on PubMed for this page, report the large trials of semaglutide and the heart. Their funding and conflicts are declared in the papers themselves.

• The heart-outcomes trial in people without diabetes (Lincoff 2023). A published trial whose figures match the FDA’s description enrolled 17,604 patients aged 45 or older with pre-existing cardiovascular disease, a body-mass index of 27 or more and no history of diabetes, and gave them once-weekly semaglutide 2.4 mg or placebo. Over a mean follow-up of 39.8 months, cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 6.5% of the semaglutide group and 8.0% of the placebo group (hazard ratio 0.80). Adverse events leading to permanent discontinuation of the trial drug occurred in 16.6% on semaglutide and 8.2% on placebo.
• The trial’s design (Ryan 2020). The design paper describes the study as a randomized, double-blind trial testing whether semaglutide 2.4 mg once weekly, added to standard care, is superior to placebo for preventing major adverse cardiovascular events in people with established cardiovascular disease and overweight or obesity but without diabetes.
• Weight over four years in the same trial (Ryan 2024). In a prespecified analysis, weight loss on semaglutide continued over 65 weeks and was sustained for up to 4 years; at 208 weeks mean weight fell 10.2% with semaglutide against 1.5% with placebo. Serious adverse events were less frequent with semaglutide in every body-mass-index group, while stopping the trial drug was more common, and more so at lower body-mass index.
• The earlier diabetes heart-safety trial (Marso 2016). In 3,297 patients with type 2 diabetes, most with established cardiovascular disease, chronic kidney disease or both, the combined outcome of cardiovascular death, nonfatal heart attack or nonfatal stroke occurred in 6.6% on weekly semaglutide (0.5 or 1.0 mg) and 8.9% on placebo. Retinopathy complications were significantly more frequent with semaglutide (hazard ratio 1.76). The site’s Cardio-Renal Protection: SGLT2 Inhibitors and GLP-1 Agonists page covers this line of research.
• The weight-loss trial (Wilding 2021). In 1,961 adults with overweight or obesity and no diabetes, mean body weight changed by −14.9% over 68 weeks with semaglutide 2.4 mg plus lifestyle intervention, against −2.4% with placebo. Nausea and diarrhea were the most common adverse events; 4.5% on semaglutide and 0.8% on placebo stopped treatment because of gastrointestinal events. The site’s GLP-1 Weight Loss Studies page covers more of these trials.
• Heart failure with preserved ejection fraction (Kosiborod 2023). In 529 patients with this form of heart failure and a body-mass index of 30 or more, 52 weeks of semaglutide 2.4 mg improved a symptom and physical-limitation score by 16.6 points against 8.7 with placebo, and lowered body weight by 13.3% against 2.6%. Serious adverse events were reported in 13.3% of the semaglutide group and 26.7% of the placebo group. The site’s Heart Failure page covers the condition.

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8. Later Steps: Liver Disease, the Shortage and Compounding

The 2025 liver-disease approval. On 15 August 2025 the FDA’s drug center announced that it had approved the same semaglutide injection to treat metabolic-associated steatohepatitis (MASH) in adults with moderate-to-advanced fibrosis (excessive scar tissue in the liver). The notice describes the injection as approved for obesity or overweight and “to reduce cardiovascular events, such as heart attacks, in individuals at high risk of these events,” the use added in 2024. The MASH approval came under the accelerated approval pathway, which the notice explains lets a therapy for a serious condition reach the market earlier based on a surrogate endpoint (such as a laboratory measure), with more data required after approval to confirm a clinically meaningful effect. At the planned 72-week interim analysis of 800 participants, 63% on semaglutide had MASH resolution with no worsening of liver scarring, against 34% on placebo; the trial is to continue for a total of 240 weeks. The site’s First MASH Liver Drug (2024) page reports the earlier 2024 approval of a different MASH drug, and the MASLD (Fatty Liver Disease) page covers the wider condition.

The shortage and compounded copies. The 2024 approval concerned the FDA-approved product only. Semaglutide injections were on the FDA drug shortage list from 2022, and during a shortage the law lets pharmacies and outsourcing facilities make copies of an approved drug. On 21 February 2025 the FDA declared the semaglutide injection shortage resolved, ending that route after grace periods; the site’s FDA Ends the Semaglutide Shortage and Compounded Copies (2025) page reports that order in full. A 2026 FDA proposal on whether semaglutide and tirzepatide may be compounded from bulk ingredients is covered on FDA Proposal on Compounded Semaglutide and Tirzepatide (2026), and the parallel 2024 tirzepatide shortage decision on Tirzepatide Shortage Ends (2024).

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9. Dates and Status as of 11 October 2026

• 8 March 2024: FDA approves the weight-management semaglutide injection to reduce the risk of cardiovascular death, heart attack and stroke in adults with cardiovascular disease and obesity or overweight.
• 21 February 2025: FDA declares the semaglutide injection shortage resolved, ending the shortage-based route for compounded copies after grace periods.
• 15 August 2025: FDA approves the same injection, under accelerated approval, for MASH with moderate-to-advanced liver fibrosis; the FDA notice restates the cardiovascular use.
• Status as of 11 October 2026: final approval in effect. The 2024 decision was a final drug approval, not a proposal. A query of the Federal Register for documents mentioning semaglutide from 1 January 2024 through 11 October 2026 found nine; none withdraws or changes this indication. They concern the 2026 list of bulk drug substances for outsourcing facilities and its comment-period extension, generic-drug product-specific guidances, a notice that one strength of the separate diabetes semaglutide injection was not withdrawn from sale for reasons of safety or effectiveness, an individual debarment order, and a Medicare and Medicaid proposed rule.

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10. Primary Documents

1. U.S. Food and Drug Administration (2024). FDA Approves First Treatment to Reduce Risk of Serious Heart Problems Specifically in Adults with Obesity or Overweight. FDA News Release, 8 March 2024 — fda.gov press announcement
2. U.S. Food and Drug Administration, Center for Drug Evaluation and Research (2025). FDA Approves Treatment for Serious Liver Disease Known as ‘MASH’. News & Events for Human Drugs, 15 August 2025 — fda.gov CDER notice

Neither action was published in the Federal Register, so there is no FR citation or docket number for either.

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Key Research Papers

1. Lincoff AM, Brown-Frandsen K, Colhoun HM, Deanfield J, Emerson SS, Esbjerg S, et al. (2023). Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. New England Journal of Medicine 389(24):2221-2232 — PubMed PMID: 37952131
2. Ryan DH, Lingvay I, Colhoun HM, Deanfield J, Emerson SS, Kahn SE, et al. (2020). Semaglutide Effects on Cardiovascular Outcomes in People With Overweight or Obesity (SELECT) rationale and design. American Heart Journal 229:61-69 — PubMed PMID: 32916609
3. Ryan DH, Lingvay I, Deanfield J, Kahn SE, Barros E, Burguera B, et al. (2024). Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Nature Medicine 30(7):2049-2057 — PubMed PMID: 38740993
4. Marso SP, Bain SC, Consoli A, Eliaschewitz FG, Jódar E, Leiter LA, et al. (2016). Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. New England Journal of Medicine 375(19):1834-1844 — PubMed PMID: 27633186
5. Wilding JPH, Batterham RL, Calanna S, Davies M, Van Gaal LF, Lingvay I, et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine 384(11):989-1002 — PubMed PMID: 33567185
6. Kosiborod MN, Abildstrøm SZ, Borlaug BA, Butler J, Rasmussen S, Davies M, et al. (2023). Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity. New England Journal of Medicine 389(12):1069-1084 — PubMed PMID: 37622681

PubMed Topic Searches

1. PubMed: semaglutide and cardiovascular outcomes in obesity
2. PubMed: GLP-1 receptor agonists and major adverse cardiovascular events
3. PubMed: semaglutide safety (pancreatitis, gallbladder)

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Connections

• FDA Actions of 2024
• FDA and Regulation
• GLP-1 Receptor Agonists
• GLP-1 Weight Loss Studies
• Cardio-Renal Protection: SGLT2 and GLP-1
• Cardiovascular Disease
• Heart Failure
• Obesity
• MASLD (Fatty Liver Disease)
• Semaglutide Shortage Ends (2025)
• Compounded Semaglutide and Tirzepatide Proposal (2026)
• Tirzepatide Shortage Ends (2024)
• First MASH Liver Drug (2024)
• Over-the-Counter Glucose Monitor (2024)

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