The short answer
Semaglutide is a GLP-1 receptor agonist; tirzepatide activates the GLP-1 receptor and the GIP receptor too. Both are FDA-approved weekly shots: semaglutide as Ozempic and Wegovy, tirzepatide as Mounjaro and Zepbound. In the SURMOUNT-5 head-to-head trial, tirzepatide produced 20.2% weight loss at 72 weeks against 13.7% for semaglutide.
Side by side
| Compared | Semaglutide | Tirzepatide |
|---|---|---|
| Category | Metabolic & GLP-1 | Metabolic & GLP-1 |
| Also known as | Ozempic, Wegovy | Mounjaro, Zepbound, LY3298176 |
| What it is | A GLP-1 receptor agonist that mimics a gut hormone your body releases after eating: it reduces appetite and slows stomach emptying. | The first dual GIP/GLP-1 receptor agonist: it activates two gut-hormone pathways at once, and in a head-to-head trial it produced more weight loss than semaglutide (20.2% vs 13.7% at 72 weeks). |
| How it works | GLP-1 receptor agonist that reduces appetite, slows gastric emptying, and improves glucose metabolism. FDA-approved for T2DM and obesity. Titrate dose slowly to minimize GI side effects. | Dual GIP/GLP-1 receptor agonist. Significantly reduces body weight through appetite suppression, slowed gastric emptying, and improved insulin sensitivity. Approved for T2DM and obesity management. |
| Commonly reported | The constant background thoughts about food ("food noise") go quiet and portions shrink without effort, with nausea worst in the first days after each dose step. FDA-approved for type 2 diabetes, weight management, heart-risk reduction and MASH, with about 15% average weight loss at 68 weeks in its main trial. | Very strong appetite suppression and meals ending early, with nausea or tiredness for a day or two after the injection, mostly after dose increases. FDA-approved for diabetes (Mounjaro) and for weight management and sleep apnea (Zepbound). |
| Studied range | FDA label: 0.25–2.4 mg, starting dose 0.25 mg. | FDA label: 2.5–15 mg, starting dose 2.5 mg. |
| How often | Weekly SubQ | Weekly |
| Half-life | ~1 week (FDA label) | ~5 days (FDA label) |
| Route | SubQ injection | SubQ injection |
| Typical run | FDA-approved for ongoing use. Community uses indefinitely or until goal weight reached, then tapers. | FDA-approved for ongoing use. Titrate slowly upward. Community maintains on minimum effective dose. |
| Evidence | Established: clinical trials or FDA-approved use exists | Established: clinical trials or FDA-approved use exists |
| Common side effects | Nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, pancreatitis risk | Nausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite, fatigue |
- Category
- SemaglutideMetabolic & GLP-1
- TirzepatideMetabolic & GLP-1
- Also known as
- SemaglutideOzempic, Wegovy
- TirzepatideMounjaro, Zepbound, LY3298176
- What it is
- SemaglutideA GLP-1 receptor agonist that mimics a gut hormone your body releases after eating: it reduces appetite and slows stomach emptying.
- TirzepatideThe first dual GIP/GLP-1 receptor agonist: it activates two gut-hormone pathways at once, and in a head-to-head trial it produced more weight loss than semaglutide (20.2% vs 13.7% at 72 weeks).
- How it works
- SemaglutideGLP-1 receptor agonist that reduces appetite, slows gastric emptying, and improves glucose metabolism. FDA-approved for T2DM and obesity. Titrate dose slowly to minimize GI side effects.
- TirzepatideDual GIP/GLP-1 receptor agonist. Significantly reduces body weight through appetite suppression, slowed gastric emptying, and improved insulin sensitivity. Approved for T2DM and obesity management.
- Commonly reported
- SemaglutideThe constant background thoughts about food ("food noise") go quiet and portions shrink without effort, with nausea worst in the first days after each dose step. FDA-approved for type 2 diabetes, weight management, heart-risk reduction and MASH, with about 15% average weight loss at 68 weeks in its main trial.
- TirzepatideVery strong appetite suppression and meals ending early, with nausea or tiredness for a day or two after the injection, mostly after dose increases. FDA-approved for diabetes (Mounjaro) and for weight management and sleep apnea (Zepbound).
- Studied range
- SemaglutideFDA label: 0.25–2.4 mg, starting dose 0.25 mg.
- TirzepatideFDA label: 2.5–15 mg, starting dose 2.5 mg.
- How often
- SemaglutideWeekly SubQ
- TirzepatideWeekly
- Half-life
- Semaglutide~1 week (FDA label)
- Tirzepatide~5 days (FDA label)
- Route
- SemaglutideSubQ injection
- TirzepatideSubQ injection
- Typical run
- SemaglutideFDA-approved for ongoing use. Community uses indefinitely or until goal weight reached, then tapers.
- TirzepatideFDA-approved for ongoing use. Titrate slowly upward. Community maintains on minimum effective dose.
- Evidence
- SemaglutideEstablished: clinical trials or FDA-approved use exists
- TirzepatideEstablished: clinical trials or FDA-approved use exists
- Common side effects
- SemaglutideNausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, pancreatitis risk
- TirzepatideNausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite, fatigue
Typical run: Community practice — opinions vary. Not a clinical recommendation.
Week by week
Each entry’s cards by day window, as the compound pages show them. Day 1 is the day you start it.
Semaglutide
- Day 1–28 · 0.25 mg Gut is adapting
- Day 29–56 · 0.5 mg Appetite shifts are real now
- Day 57–112 · 1 mg Clinically useful weight loss kicks in
- Day 113–140 · 1.7 mg Max submaximal step
- Day 141–364 · 2.4 mg Full dose — the working dose
- Day 365+ Plateau territory — new baseline
Tirzepatide
- Day 1–28 · 2.5 mg Getting your gut acclimated
- Day 29–56 · 5 mg First therapeutic dose — weight drops
- Day 57–112 · 7.5 mg Dual agonism in full effect
- Day 113–168 · 12.5 mg Max titration reached
- Day 169–504 Weeks 24 to 72: where most people plateau
- Day 365+ A maintenance medication, not a course
Together or one or the other
The library marks semaglutide and tirzepatide as not combined.
Questions people ask
How long do semaglutide and tirzepatide last?
The half-life of semaglutide is ~1 week (FDA label). The half-life of tirzepatide is ~5 days (FDA label).
How often are semaglutide and tirzepatide taken?
Semaglutide: weekly SubQ. Route: SubQ injection. Tirzepatide: weekly. Route: SubQ injection.
How are semaglutide and tirzepatide dosed in research?
The FDA label range for semaglutide is 0.25–2.4 mg, with a 0.25 mg starting dose. The FDA label range for tirzepatide is 2.5–15 mg, with a 2.5 mg starting dose.
What are the common side effects of semaglutide and tirzepatide?
For semaglutide, the library lists: nausea, vomiting, diarrhea, constipation, decreased appetite, fatigue, pancreatitis risk. For tirzepatide: nausea, diarrhea, vomiting, constipation, abdominal pain, decreased appetite, fatigue.
Are semaglutide and tirzepatide taken together?
No. The library marks semaglutide and tirzepatide as not combined.
Each one in full
PepVault for iPhone
Track either one in PepVault
Log every dose of semaglutide or tirzepatide, with reminders on your schedule. 7 days free on the yearly plan for new subscribers.
