Semaglutide
GLP-1 Receptor Agonist · Ozempic · Wegovy · Rybelsus
What is Semaglutide?
Semaglutide is a 94% homologous analog of human GLP-1 with a C18 fatty acid chain that enables albumin binding, extending the half-life from minutes (native GLP-1) to ~7 days. Approved as Ozempic (2017, T2D), Wegovy (2021, obesity), and Rybelsus (oral, 2019, T2D), it is one of the most commercially successful drugs in pharmaceutical history.
Semaglutide reduces appetite centrally, slows gastric emptying, and stimulates glucose-dependent insulin secretion. Unlike older weight loss drugs, it works through an incretin-based mechanism that also provides direct cardiovascular benefits.
Research Evidence
STEP 1: 14.9% average weight loss at 2.4 mg/week vs 2.4% placebo over 68 weeks. STEP 5 (2-year): 15.2% sustained weight loss.
HbA1c reductions of 1.5–1.8% across SUSTAIN trials. Superior to sitagliptin, exenatide, and insulin glargine in head-to-head trials.
20% relative risk reduction in major adverse cardiovascular events in overweight/obese adults without diabetes.
~25–35% of weight lost is lean mass. Active resistance training and protein ≥1.2g/kg significantly attenuates this. Some clinicians add ipamorelin/CJC-1295 for GH-mediated muscle preservation.
Wegovy Titration Schedule
| Weeks | Dose | Notes |
|---|---|---|
| 1–4 | 0.25 mg/wk | Always start here |
| 5–8 | 0.5 mg/wk | |
| 9–12 | 1.0 mg/wk | Meaningful weight loss begins |
| 13–16 | 1.7 mg/wk | |
| 17+ | 2.4 mg/wk | Target therapeutic dose |
Frequently Asked Questions
What is semaglutide?
A once-weekly GLP-1 receptor agonist FDA-approved as Ozempic (T2D) and Wegovy (weight loss). Reduces appetite, slows gastric emptying, improves insulin sensitivity.
How much weight does semaglutide cause you to lose?
Average 14.9% body weight at 2.4 mg/week over 68 weeks (STEP 1). ~34 lbs for a 230 lb person. Individual results vary.
Semaglutide vs tirzepatide?
Tirzepatide produces ~47% more weight loss (22.5% vs 14.9%) due to its additional GIP receptor activity. Semaglutide is generally more available and less expensive.
How do I preserve muscle on semaglutide?
Resistance training 3–4x/week, protein ≥1.2–1.6g/kg body weight, adequate calories above 1,200 kcal/day. Some clinicians add ipamorelin/CJC-1295 for GH-mediated muscle preservation.
This profile was prepared using AI-assisted research synthesis. Citations are provided where applicable — verify with primary sources before clinical application.