PeptideInjectableIncretin agonistGIP/GLP-1Peptide
Tirzepatide
Also known as Mounjaro · Zepbound · LY3298176
A once-weekly dual GIP/GLP-1 receptor agonist licensed for type 2 diabetes and obesity. Produces the largest mean weight loss of any approved agent to date, at the cost of a dose-limiting gastrointestinal side-effect profile.
01 Overview
Tirzepatide activates two incretin receptors rather than one, which appears to underlie its larger effect on weight and glycaemia than single-agonist GLP-1 drugs.
The headline weight-loss figures are trial-grade and robust; the practical story is tolerability and what happens to lean mass when weight comes off quickly.
02 Mechanism
A synthetic 39-amino-acid peptide that agonises both the GIP and GLP-1 receptors. The combined action slows gastric emptying, enhances glucose-dependent insulin secretion, and reduces appetite through central pathways.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Starting | 2.5 mg/wk | SubQ | Four-week initiation dose; not intended to be therapeutic, it exists to build tolerance. |
| Maintenance | 5–10 mg/wk | SubQ | Titrated upward in 2.5 mg steps no more often than every 4 weeks. |
| Maximum | 15 mg/wk | SubQ | Highest licensed dose; largest effect and highest discontinuation rate. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Weight lossSURMOUNT-1: mean 20.9% at 15 mg — the largest for any approved agent | ~20% at 72 weeks | Clinical | |
| Glycaemic controlSuperior to semaglutide in head-to-head trial (SURPASS-2) | HbA1c −2.0 to −2.3% | Clinical | |
| Appetite reductionCentral mechanism; the proximate cause of the weight effect | Marked | Clinical | |
| Improved cardiovascular markersOutcome trial (SURPASS-CVOT) reported; hard-endpoint data still maturing | BP, lipids | Observational |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal effectsNausea, vomiting, diarrhoea and constipation — the dose-limiting effect and the main driver of discontinuation. | Moderate | Very common | Clinical | |
| Lean mass lossA substantial fraction of rapid weight loss is lean tissue, as with any large calorie deficit. | Moderate | Common | Clinical | |
| Gallbladder diseaseCholelithiasis and cholecystitis, associated with rapid weight loss generally rather than the drug specifically. | Moderate | Uncommon | Clinical | |
| PancreatitisA rare but serious class-associated signal for incretin drugs. | Severe | Rare | Observational |
06 Commonly used with
What tirzepatide is combined with, and why. This is about intent rather than safety — the interactions table below covers what is dangerous. Nothing here is listed without what it costs.
| Compound | Frequency | Purpose & trade-off |
|---|---|---|
| Stacked compounds | ||
| Semaglutide or retatrutideswitch between incretins | Users occasionally switch among incretin agonists (rather than truly co-dosing) seeking a plateau-breaking response or the latest agent's added mechanism.Trade-off: Overlapping two incretins compounds GI side effects and hypoglycaemia risk with insulin/sulfonylureas and offers no established advantage over a clean switch and dose titration. | |
| Support & ancillaries | ||
| Metformininsulin-sensitiser | Combined for additive glycaemic control and weight effect, since metformin's insulin-sensitising action complements tirzepatide's incretin mechanism.Trade-off: The GI burden of both together (nausea, diarrhoea) can be significant, and the compounded appetite loss increases the risk of inadequate protein intake and lean-mass loss. | |
| Resistance training + high-protein dietmuscle preservation | Paired with a tirzepatide cut because its powerful appetite suppression drives a deep deficit that will otherwise cost a meaningful share of lean mass.Trade-off: The drug's strong satiety effect makes eating enough protein difficult, so the intervention needed to protect muscle directly conflicts with how the drug works. | |
| Antiemetic + hydration/fibre supportGI management | Used during dose escalation to control the nausea, vomiting and constipation that are tirzepatide's dose-limiting effects.Trade-off: It manages symptoms rather than the underlying cause and can mask warning signs of more serious issues like pancreatitis or gallbladder disease. | |
07 Legal status
United States
Prescription only
FDA approved · as of Jan 2026
United Kingdom
Prescription only (POM)
as of Jan 2026
Germany
Prescription only (AMG)
as of Jan 2026
08 References
Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1)N Engl J Med, 2022
Tirzepatide versus semaglutide once weekly in type 2 diabetes (SURPASS-2)N Engl J Med, 2021
09 Discussion0 comments
Discussion is moderated. No sourcing, vendor names or price talk — those comments are removed, and repeat posts are banned.
This page is reference information, not medical advice. Doses and protocols are documented as they appear in the clinical literature and in practice — describing them is not a recommendation to use them. Countermeasures listed here are not a substitute for a physician. Legal status varies by jurisdiction and changes.