Semaglutide
Semaglutide is an FDA-approved GLP-1 receptor agonist marketed as Ozempic (type 2 diabetes, cardiovascular risk reduction) and Wegovy (chronic weight management), backed by large phase-3 trial programs (STEP, SUSTAIN).
Semaglutide reconstitution calculator
Open full calculator →Typical dosing
| Goal | Range | Route | Frequency |
|---|---|---|---|
| Initiation (GI tolerability) | 0.25 mg | SubQ, abdomen/thigh/upper arm | Once weekly, weeks 1-4 (not a therapeutic dose) |
| Titration step 1 | 0.5 mg | SubQ weekly | Weeks 5-8 |
| Titration step 2 | 1 mg | SubQ weekly | Weeks 9-12 |
| Titration step 3 (Wegovy only) | 1.7 mg | SubQ weekly | Weeks 13-16 |
| Maintenance — weight management (Wegovy) | 2.4 mg | SubQ weekly | Week 17 onward, ongoing |
| Maintenance — glycemic control (Ozempic) | 0.5-2 mg | SubQ weekly | Per FDA label, after initial titration; max 2 mg/week |
Ranges compiled from research literature — not a prescription.
How it works
Semaglutide is a synthetic analog of human glucagon-like peptide-1 (GLP-1), modified with a fatty-diacid side chain and amino-acid substitutions that confer resistance to DPP-4 degradation and reversible albumin binding, producing an elimination half-life of roughly one week that supports once-weekly dosing. As a GLP-1 receptor agonist, it binds GLP-1 receptors on pancreatic beta cells, the hypothalamus, and the gut.
Pharmacologically, semaglutide increases glucose-dependent insulin secretion, suppresses glucagon release, slows gastric emptying, and acts on hypothalamic appetite centers to reduce hunger and food intake. The combined effect on satiety and gastric emptying is the primary driver of weight loss, while the insulinotropic and glucagonostatic effects drive glycemic control in type 2 diabetes.
The evidence base is unusually large for a peptide drug. In the STEP 1 trial (1,961 adults with overweight/obesity, no diabetes), semaglutide 2.4 mg produced a mean 14.9% body-weight reduction versus 2.4% with placebo at 68 weeks, with 86.4% of treated participants losing at least 5% of body weight. STEP 1 extension data showed most of the lost weight was regained within a year of stopping treatment, underscoring that effects are dependent on continued use. In SUSTAIN-6 (3,297 adults with type 2 diabetes and high cardiovascular risk), semaglutide reduced the composite endpoint of cardiovascular death, nonfatal MI, or nonfatal stroke by 26% versus placebo (HR 0.74, 95% CI 0.58-0.95) over ~2 years, supporting the cardiovascular risk-reduction indication later added to the Ozempic label.
Because of this trial base, semaglutide carries full FDA approval and is legally available only by prescription in FDA-regulated, quality-controlled pen formulations (Ozempic, Wegovy) or tablets (Rybelsus). This is a meaningfully different risk profile from "research" or compounded semaglutide sold outside the pharmacy system, which is not FDA-approved, is not manufactured or tested under the same quality standards, and falls outside the dosing, monitoring, and pharmacovigilance framework established in the trials above.
Side effects & safety
- Gastrointestinal effects are the most common adverse reactions: nausea (~44% vs 16% placebo), vomiting (~25% vs 6%), and diarrhea (~30% vs 16%) in Wegovy weight-management trials; these are the leading cause of discontinuation.
- Boxed warning: in rodent studies semaglutide caused thyroid C-cell tumors; it is unknown whether this occurs in humans, so semaglutide is contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
- Acute pancreatitis has been reported in patients treated with semaglutide and other GLP-1 receptor agonists; discontinue promptly if pancreatitis is suspected.
- Increased risk of gallbladder disease (cholelithiasis, cholecystitis), likely related to rapid weight loss, has been observed in weight-management trials.
- Contraindicated with hypersensitivity to semaglutide or any product component, in addition to the MTC/MEN 2 contraindication above; use with caution alongside insulin or sulfonylureas due to hypoglycemia risk, and monitor renal function and diabetic retinopathy status in patients with type 2 diabetes.
- Legally requires a prescription, medical evaluation, and clinician-supervised dose titration and monitoring — it is not an over-the-counter or self-directed research chemical.
Research
Primary sources — PubMed.
- FDA. Highlights of Prescribing Information: OZEMPIC (semaglutide) injection. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209637s025lbl.pdf
- FDA. Highlights of Prescribing Information: WEGOVY (semaglutide) injection. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215256s024lbl.pdf
- Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). N Engl J Med. 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
- Marso SP, et al. Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6). N Engl J Med. 2016. https://www.nejm.org/doi/full/10.1056/NEJMoa1607141
- Wilding JPH, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542252/
- Overgaard RV, et al. Clinical Pharmacokinetics of Semaglutide: A Systematic Review. Drug Des Devel Ther. 2021. https://www.dovepress.com/clinical-pharmacokinetics-of-semaglutide-a-systematic-review-peer-reviewed-fulltext-article-DDDT
- Husain M, et al. Cardiovascular Safety and Benefits of Semaglutide in Patients With Type 2 Diabetes: Findings From SUSTAIN 6 and PIONEER 6. Front Endocrinol. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8039387/
- Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nat Med. 2022. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556320/