Dr. Pep

Peptides · GLP-1 receptor agonist

Semaglutide: what the studies show

Every line below comes from a study, label or regulator record, checked by two models, with the source linked. Information, not medical advice. For adults 18+.

What it is

  • Semaglutide is a GLP-1 receptor agonist. It comes as a weekly injection (Ozempic for type 2 diabetes; Wegovy for weight and heart risk) and as daily tablets (Rybelsus and Ozempic tablets for type 2 diabetes; Wegovy tablets for weight and heart risk).[1][2][3]
  • The Ozempic injection label (June 2026) lists three uses in adults with type 2 diabetes: blood-sugar control, fewer major heart events in those with heart disease, and slower kidney decline in those with chronic kidney disease.[1]
  • The Wegovy label (June 2026) covers the injection and the tablets. Both are for fewer major heart events in adults with heart disease plus obesity or overweight, and for weight loss and long-term maintenance, alongside a reduced-calorie diet and more activity. The injection is also for children 12 and older with obesity, and for the liver disease MASH with moderate-to-advanced fibrosis in adults, under accelerated approval that depends on a confirmatory trial.[2]

Bottom line

  • Semaglutide is an approved prescription drug with large randomised trials showing weight loss and fewer heart events, but the benefit is tied to staying on it, nausea and vomiting are common, and compounded or 'research' vials are not FDA-reviewed products.[4][5][6][2][7]

What the human studies found

  • STEP 1 (double-blind RCT, 1,961 adults with obesity or overweight and no diabetes, with lifestyle support): after 68 weeks on semaglutide 2.4 mg weekly, body weight fell 14.9% versus 2.4% on placebo. 69.1% lost 10% or more versus 12.0% on placebo.[4]
  • STEP 5 (RCT, 304 adults without diabetes): weight change at 104 weeks was -15.2% on semaglutide 2.4 mg, so the loss held over two years while treatment continued.[8]
  • STEP 8 (RCT, 338 adults without diabetes, 68 weeks): weekly semaglutide gave -15.8% body weight versus -6.4% for daily liraglutide. Gastrointestinal side effects were reported by 84.1% on semaglutide and 82.7% on liraglutide.[9]
  • Stopping matters. In the STEP 1 extension (327 people), those who stopped semaglutide and lifestyle support regained 11.6 percentage points of body weight within a year, about two-thirds of what they had lost. In STEP 4 (803 people), switching to placebo after a 20-week run-in gave +6.9% weight change, versus -7.9% for those who continued.[6][10]
  • SELECT (RCT, 17,604 adults with heart disease and overweight or obesity but no diabetes, mean follow-up 39.8 months): heart death, non-fatal heart attack or non-fatal stroke occurred in 6.5% on semaglutide 2.4 mg versus 8.0% on placebo (hazard ratio 0.80). Stopping the drug because of side effects was twice as common: 16.6% versus 8.2%.[5]
  • SUSTAIN 6 (RCT, 3,297 adults with type 2 diabetes at high heart risk, semaglutide 0.5 or 1 mg weekly): the main heart outcome occurred in 6.6% versus 8.9% on placebo (hazard ratio 0.74). Eye complications of diabetic retinopathy were more common on semaglutide (hazard ratio 1.76).[11]

Known risks and side effects

  • Boxed warning on both labels: risk of thyroid C-cell tumours, including medullary thyroid cancer. Not for anyone with a personal or family history of medullary thyroid cancer or MEN 2.[2][1]
  • In the Wegovy label's adult injection trials, nausea was 44% versus 16% on placebo, diarrhoea 30% versus 16%, vomiting 24% versus 6%, constipation 24% versus 11%. 6.8% stopped because of side effects versus 3.2% on placebo.[2]
  • Other label warnings: acute pancreatitis, gallbladder disease, low blood sugar with insulin or sulfonylureas, acute kidney injury (often after vomiting or diarrhoea), serious allergic reactions, worsening diabetic retinopathy, and higher heart rate. The Ozempic label adds pulmonary aspiration during anaesthesia or deep sedation.[2][1]
  • A meta-analysis of GLP-1 drugs found no clear rise in bowel obstruction or ileus overall (odds ratio 1.95, 95% CI 0.43-8.79). It found a higher risk with liraglutide than with semaglutide.[12]
  • FDA has received reports of overdoses, some needing hospital care, from dosing errors with compounded semaglutide vials. Patients drew up the wrong dose or mixed up mL, mg and 'units'. Overdose can cause severe nausea, vomiting and low blood sugar, and semaglutide's half-life is about one week.[13]

Legal status

  • FDA approved: Ozempic and Wegovy injections and Rybelsus tablets (FDA alert on dosing errors, 2026; labels dated 2026).[13][1][2]
  • On 2025-02-21 FDA declared the semaglutide injection shortage resolved. FDA's page dated 2026-04-01 says compounders must meet the section 503A and 503B conditions. A 503A compounder generally cannot make routine essential copies of a commercially available drug. FDA says it does not intend to act if a compounder fills four or fewer such prescriptions a month.[14][15]
  • FDA says compounded GLP-1 drugs are not reviewed for safety, effectiveness or quality, and should be used only when an approved drug cannot meet the patient's need (page updated 2026).[7]

Sources

  1. [1] Ozempic (Semaglutide) Injection, Solution prescribing information
  2. [2] Wegovy (Semaglutide) Injection, Solution Wegovy (Semaglutide) Tablet prescribing information
  3. [3] Ozempic (Oral Semaglutide) Tablet Rybelsus (Oral Semaglutide) Tablet prescribing information
  4. [4] Once-Weekly Semaglutide in Adults with Overweight or Obesity.
  5. [5] Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes.
  6. [6] Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension.
  7. [7] FDA: FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss (updated 2026)
  8. [8] Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial.
  9. [9] Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial.
  10. [10] Effect of Continued Weekly Subcutaneous Semaglutide vs Placebo on Weight Loss Maintenance in Adults With Overweight or Obesity: The STEP 4 Randomized Clinical Trial.
  11. [11] Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes.
  12. [12] Evaluating bowel obstruction and ileus events in patients on GLP-1 receptor agonists: a systematic review and meta-analysis.
  13. [13] FDA: FDA alerts health care providers, compounders and patients of dosing errors associated with compounded injectable semaglutide products
  14. [14] FDA: Declaratory Order, Resolution of Shortages of Semaglutide Injection Products (2025-02-21)
  15. [15] FDA: FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize (shortage resolution, end of enforcement discretion)