Comparison
Semaglutide vs Tirzepatide
Side-by-side of Semaglutide and Tirzepatide. Every row below is pulled from the compound schema and will update as our data grows. For deeper reads, follow through to each compound page.
Semaglutide
Semaglutide for weight loss: GLP-1 agonist (Ozempic, Wegovy) drives 15-17% mean loss at 2.4 mg/week in STEP trials. Watch lean-mass loss.
Tirzepatide
Tirzepatide for weight loss: dual GIP/GLP-1 agonist sold as Mounjaro and Zepbound. SURMOUNT-1 showed 22.5% mean body-weight loss at 15 mg over 72 weeks.
Effects at a glance
Semaglutide
- •Long-acting GLP-1 receptor agonist with a ~7-day half-life that supports once-weekly subcutaneous dosing
- •STEP trials reported ~15 to 17% mean body-weight loss at 2.4 mg/week over 68 weeks in adults with obesity
- •Lowers HbA1c by ~1.0 to 1.8 percentage points in type 2 diabetes versus placebo
- •SELECT trial showed reduced major cardiovascular events in adults with prior CVD and overweight or obesity
- •Up to 25 to 40% of weight lost can be lean mass; pairing with resistance training and protein intake mitigates this
- •GI effects (nausea, vomiting, constipation) drive most discontinuations and ease with slow titration
Tirzepatide
- •Dual GIP plus GLP-1 receptor agonist with a ~5-day half-life supporting once-weekly subcutaneous dosing
- •SURMOUNT-1 reported ~22.5% mean body-weight loss at 15 mg over 72 weeks versus 2.4% on placebo
- •Lowers HbA1c by ~1.9 to 2.6 percentage points in type 2 diabetes across SURPASS trials
- •Outperformed semaglutide 1.0 mg head-to-head on weight loss and HbA1c in SURPASS-2
- •GI effects (nausea, diarrhea, vomiting) drive most discontinuations and ease with slow titration
- •Lean-mass loss observed in body-composition substudies; resistance training and protein intake mitigate this
Side-by-side
| Attribute | Semaglutide | Tirzepatide |
|---|---|---|
| Category | pharmaceutical | pharmaceutical |
| Also known as | Ozempic, Wegovy, Rybelsus | Mounjaro, Zepbound, LY3298176 |
| Half-life (hr) ↗ | 168 | 120 |
| Typical dose (mg) ↗ | 2.4 | 10 |
| Dosing frequency | weekly (SC); daily (oral Rybelsus) | weekly |
| Routes | subcutaneous, oral | subcutaneous |
| Onset (hr) | 24 | 24 |
| Peak (hr) | 72 | 72 |
| Molecular weight | 4113.58 | 4813.45 |
| Molecular formula | - | C225H348N48O68 |
| Mechanism | Long-acting GLP-1 receptor agonist; potentiates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts on hypothalamic satiety centers. | Synthetic 39-amino-acid peptide that activates both GIP and GLP-1 receptors. Potentiates glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and acts on hypothalamic and brainstem satiety circuits. |
| Legal status | Prescription only (FDA-approved, EMA-approved) | Prescription only; FDA-approved 2022 (T2DM, Mounjaro) and 2023 (chronic weight management, Zepbound) |
| WADA status | allowed | allowed |
| DEA / Rx | Rx only (not a controlled substance); FDA-approved for type 2 diabetes (2017) and chronic weight management (2021) | Rx only (not a controlled substance) |
| Pregnancy | Not recommended; discontinue 2 months before planned pregnancy | Not recommended; discontinue 2 months before planned pregnancy |
| CAS | 910463-68-2 | 2023788-19-2 |
| PubChem CID | 56843331 | 156588324 |
| Wikidata | Q27089394 | Q105099794 |
Safety profile
Semaglutide
Common side effects
- nausea
- vomiting
- diarrhea
- constipation
- decreased appetite
- injection-site reactions
- fatigue
Contraindications
- personal or family history of medullary thyroid carcinoma
- multiple endocrine neoplasia type 2
- pregnancy
- history of pancreatitis (use caution)
Interactions
- insulin: additive hypoglycemia risk; insulin dose typically reduced(major)
- sulfonylureas (glipizide, glyburide): hypoglycemia risk, sulfonylurea dose often reduced(major)
- oral medications (general): delayed gastric emptying can alter absorption kinetics(moderate)
- warfarin: monitor INR due to altered absorption(moderate)
Tirzepatide
Common side effects
- nausea
- diarrhea
- vomiting
- constipation
- decreased appetite
- injection-site reactions
- fatigue
- abdominal pain
Contraindications
- personal or family history of medullary thyroid carcinoma
- multiple endocrine neoplasia type 2
- pregnancy
- history of pancreatitis (use caution)
- severe gastroparesis
Interactions
- insulin: additive hypoglycemia risk; insulin dose typically reduced(major)
- sulfonylureas (glipizide, glyburide): hypoglycemia risk, sulfonylurea dose often reduced(major)
- oral medications (general): delayed gastric emptying can alter absorption kinetics(moderate)
- oral contraceptives: reduced exposure after first dose; backup contraception recommended for 4 weeks after initiation and each dose escalation(moderate)
- warfarin: monitor INR due to altered absorption(moderate)
Which Should You Take?
Semaglutide and Tirzepatide score evenly on the criteria we weight (goal breadth, legal accessibility, evidence depth). The conditionals below should drive the decision more than any aggregate score.
- → If your priority is glycemic control, pick Tirzepatide.
- → If your priority is metabolic health and glucose control, pick Semaglutide.
- → If your priority is fat loss, pick Semaglutide.
Edge case: If you cannot self-administer injections, Semaglutide is the only oral option in this pair.
Default choice: either is defensible. Semaglutide edges out on goal breadth + legal accessibility; Tirzepatide is the right call if your priority sits in the goals listed above.
This verdict is generated from each compound's schema (goals, legal status, evidence outcomes, dosing route). It updates automatically as our compound data evolves; the deeper read sits on each individual compound page.
Common questions
What is the difference between Semaglutide and Tirzepatide?
Semaglutide and Tirzepatide differ in category (pharmaceutical vs pharmaceutical), mechanism, and typical dosing. See the side-by-side table for full details.
Which has a longer half-life, Semaglutide or Tirzepatide?
Semaglutide half-life is 168 hours; Tirzepatide half-life is 120 hours.
Can you stack Semaglutide with Tirzepatide?
Stack compatibility depends on mechanism overlap, legal status, and individual response. Check each compound page for specific interactions and contraindications before combining.
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