Compound reference
Semaglutide
Also known as Ozempic, Wegovy, Rybelsus
A once-weekly GLP-1 receptor agonist and the most heavily evidenced compound here — approved for type 2 diabetes and obesity, and shown to cut cardiovascular events even in people without diabetes.
- CAS
- 910463-68-2
- Molar mass
- ≈4,114 g/mol
- Half-life
- About 7 days (once-weekly)
Approved prescription medicine in several jurisdictions for labeled indications including type 2 diabetes and chronic weight management.
Mode of action
Semaglutide is a long-acting GLP-1 receptor agonist — an analogue sharing about 94% homology with human GLP-1, acylated with a C18 fatty-diacid chain that binds albumin and stretches its half-life to roughly a week (once-weekly subcutaneous injection; an oral form is co-formulated with the absorption enhancer SNAC for once-daily dosing).
Through the GLP-1 receptor it enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts in the brain to reduce appetite and energy intake. Those effects together account for both its glycemic and weight-loss benefits, and — as the outcome trials showed — a cardiovascular benefit that is only partly explained by weight loss.
Main intended effect
Glycemic control in type 2 diabetes and weight reduction in obesity, with an established reduction in major cardiovascular events on top of both.
Areas of interest
The core indications are type 2 diabetes and obesity. Beyond them, the evidence has pushed into cardiovascular prevention (including in people without diabetes), heart failure with preserved ejection fraction, and chronic kidney disease, with more speculative interest in metabolic liver disease and neurodegenerative conditions. It is also the GLP-1 partner in combination products such as CagriSema.
Evidence for intended effects
Semaglutide has the deepest evidence base of any compound here, and it is the only one approved. The STEP program established weight loss of roughly 15–17% in adults with obesity without diabetes and about 10% with type 2 diabetes. The SUSTAIN program established glycemic and cardiovascular benefit in type 2 diabetes, and SELECT then showed a ~20% reduction in major cardiovascular events in people with obesity but without diabetes — a landmark result. The oral formulation reproduced the cardiovascular benefit (SOUL), and semaglutide improved symptoms in obesity-related HFpEF. The boundary is real too: a Phase 2 trial in NASH-related cirrhosis did not improve fibrosis or resolve NASH.
| Indication | Strongest evidence | Result |
|---|---|---|
| Obesity (no diabetes) | Phase 3 STEP 1 | ~15% weight loss |
| Type 2 diabetes | SUSTAIN-6 + STEP 2 | glycemic control + ~10% weight loss |
| Cardiovascular (obesity, no diabetes) | SELECT (NEJM 2023) | MACE hazard ratio 0.80 |
| Cardiovascular (T2D, oral) | SOUL (NEJM 2025) | MACE hazard ratio 0.86 |
| NASH-related cirrhosis | Phase 2 (Lancet GH 2023) | no fibrosis/NASH benefit |
Studied amounts (literature dosing context)
Semaglutide is given as a once-weekly subcutaneous injection or a once-daily oral tablet, titrated up to limit gastrointestinal effects. The amounts in the trials and labels are: subcutaneous 2.4 mg weekly for chronic weight management, up to 2.0 mg weekly for type 2 diabetes, and oral 14 mg daily. Because semaglutide is an approved medicine, dosing should follow the prescribing information and a clinician — this page is reference context, not medical advice.
Safety and regulatory status
Semaglutide is an approved prescription medicine — cleared in the United States for type 2 diabetes (Ozempic, 2017), chronic weight management (Wegovy, 2021), and as an oral tablet (Rybelsus), and approved across many other jurisdictions. Its safety is well characterised: gastrointestinal effects (nausea, vomiting, diarrhea) are common and usually transient, with raised rates of gallbladder/biliary events, pancreatitis monitoring, and a class boxed warning for thyroid C-cell tumours based on rodent data.
The caution specific to this platform is sourcing: compounded or online "semaglutide" is not the approved product, and its dose and purity are not assured.
Sources
A Pharmacological and Clinical Overview of Oral Semaglutide for the Treatment of Type 2 Diabetes
Narrative review (Andersen, Knop, and Vilsbøll, Drugs, 2021) of oral semaglutide — a co-formulation of the semaglutide peptide with the absorption enhancer SNAC that enables oral dosing despite the acidic gastric environment. It describes semaglutide as a GLP-1 receptor agonist sharing 94% homology with human GLP-1, and summarizes the PIONEER phase 3 program showing improved glycemic control, weight loss, and reduced systolic blood pressure. Useful for the oral formulation's pharmacology and clinical profile.
Efficacy and safety of semaglutide for weight management: a systematic review and meta-analysis
Systematic review and meta-analysis published in the BMJ evaluating randomized controlled trials of semaglutide for weight management in adults. The review synthesizes evidence across injectable and oral formulations, examining changes in body weight, BMI, and waist circumference alongside safety and tolerability outcomes. Gastrointestinal adverse events were the most frequently reported treatment-related effects, consistent with the GLP-1 receptor agonist drug class. The authors concluded that semaglutide produces clinically meaningful weight reduction but emphasized the need for additional long-term data on cardiovascular and other outcomes beyond weight change.
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Phase 3 STEP 1 double-blind RCT (Wilding et al., NEJM 2021) randomizing 1,961 adults with BMI ≥30 or ≥27 with comorbidities but without diabetes 2:1 to once-weekly subcutaneous semaglutide 2.4 mg or placebo, both combined with lifestyle intervention, for 68 weeks. Semaglutide produced a mean body-weight reduction of 14.9% versus 2.4% with placebo (difference −12.4 percentage points; 95% CI −13.4 to −11.5; p<0.001). Achievement of ≥5%, ≥10%, and ≥15% weight loss was 86.4% vs 31.5%, 69.1% vs 12.0%, and 50.5% vs 4.9% respectively (all p<0.001). Gastrointestinal events were the most common adverse effects; 4.5% of semaglutide versus 0.8% of placebo participants discontinued due to GI adverse events. The trial established semaglutide 2.4 mg as a highly effective weight-management agent in people without diabetes.
Semaglutide 2.4 mg once a week in adults with overweight or obesity, and type 2 diabetes (STEP 2)
Phase 3, randomized, double-blind, placebo-controlled trial (Davies and colleagues, The Lancet, 2021) of once-weekly subcutaneous semaglutide 2.4 mg in adults with overweight or obesity and type 2 diabetes. Mean body-weight change from baseline to week 68 was −9.6% with semaglutide 2.4 mg versus −3.4% with placebo (and −7.0% with semaglutide 1.0 mg), alongside an HbA1c reduction of about 1.6% and improved cardiometabolic risk factors. Gastrointestinal events were the most common adverse effects.
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6)
Phase 3, randomized, double-blind, placebo-controlled cardiovascular-outcomes trial (Marso and colleagues, New England Journal of Medicine, 2016) of once-weekly subcutaneous semaglutide (0.5 or 1.0 mg) over 104 weeks in 3,297 patients with type 2 diabetes at high cardiovascular risk. Semaglutide significantly reduced the primary composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke and lowered HbA1c versus placebo. This was the foundational cardiovascular-outcomes trial establishing semaglutide's macrovascular benefit in type 2 diabetes.
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes (SELECT)
Phase 3, randomized, double-blind, placebo-controlled cardiovascular-outcomes trial (Lincoff and colleagues, New England Journal of Medicine, 2023) of once-weekly subcutaneous semaglutide 2.4 mg in 17,604 adults aged 45+ with established cardiovascular disease and overweight or obesity but without diabetes. Over a mean 39.8 months, semaglutide reduced the primary composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (hazard ratio 0.80). SELECT was the first trial to show a GLP-1 receptor agonist cuts cardiovascular events in people with obesity but without diabetes; gastrointestinal effects drove more discontinuations than placebo.
Oral Semaglutide and Cardiovascular Outcomes in High-Risk Type 2 Diabetes (SOUL)
Phase 3, randomized, double-blind, placebo-controlled cardiovascular-outcomes trial (McGuire and colleagues, New England Journal of Medicine, 2025) of once-daily oral semaglutide (up to 14 mg) in adults with type 2 diabetes and established atherosclerotic cardiovascular disease and/or chronic kidney disease. Oral semaglutide significantly reduced major adverse cardiovascular events (cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke), hazard ratio 0.86 — a 14% relative risk reduction — extending the injectable cardiovascular benefit to the oral formulation.
Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes (STEP-HFpEF DM)
Randomized, double-blind, placebo-controlled trial (Kosiborod and colleagues, New England Journal of Medicine, 2024) of once-weekly subcutaneous semaglutide 2.4 mg over 52 weeks in patients with obesity-related heart failure with preserved ejection fraction (HFpEF) and type 2 diabetes. Semaglutide produced larger improvements in heart-failure symptoms (KCCQ-CSS 13.7 vs 6.4 points) and greater weight loss (9.8% vs 3.4%) than placebo, with favorable secondary outcomes including 6-minute walk distance and C-reactive protein.
Semaglutide 2.4 mg once weekly in patients with NASH-related cirrhosis: a randomised, placebo-controlled phase 2 trial
Phase 2, randomized, double-blind, placebo-controlled trial (Loomba and colleagues, The Lancet Gastroenterology & Hepatology, 2023) of once-weekly subcutaneous semaglutide 2.4 mg over 48 weeks in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH)-related compensated cirrhosis and BMI ≥27. Semaglutide did not significantly improve liver fibrosis or achieve NASH resolution versus placebo — an important negative result bounding its hepatic claims. The safety profile was consistent with the class (nausea, diarrhea, vomiting), with no new hepatic or renal safety signals.
Safety of semaglutide
Safety review (Smits and Van Raalte, Frontiers in Endocrinology, 2021) drawing on the SUSTAIN (subcutaneous) and PIONEER (oral) phase 3 and cardiovascular-outcome programs. It examines gastrointestinal effects, hypoglycemia, pancreatic safety (pancreatitis, pancreatic cancer), thyroid C-cell tumors, and gallbladder/biliary events. The authors conclude semaglutide mostly causes mild-to-moderate transient gastrointestinal disturbance and a raised risk of biliary disease (cholelithiasis), with an overall favorable risk/benefit profile in type 2 diabetes.
OZEMPIC (semaglutide) injection, for subcutaneous use — Prescribing Information
Official FDA-approved prescribing information for Ozempic (semaglutide injection) for subcutaneous use, originally approved December 5, 2017 and subsequently updated. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. The label carries a boxed warning regarding the risk of thyroid C-cell tumors, including medullary thyroid carcinoma, observed in rodent studies and contraindicates use in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Clinical efficacy and safety are supported by the SUSTAIN phase 3 clinical trial program. The prescribing information provides dosing schedules, drug interaction guidance, and safety monitoring recommendations applicable to clinical use.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209637lbl.pdf