Compound reference
Tirzepatide
Also known as LY3298176, Mounjaro, Zepbound
A once-weekly dual GIP/GLP-1 receptor agonist — approved for type 2 diabetes and obesity, and the most effective single approved agent for weight loss to date, having beaten semaglutide head-to-head.
- CAS
- 2023788-19-2
- Formula
- C225H348N48O68
- Molar mass
- ≈4,813 g/mol
- Half-life
- About 5 days (once-weekly)
Approved prescription medicine in several jurisdictions for labeled indications including type 2 diabetes and chronic weight management.
Mode of action
Tirzepatide is a single engineered peptide that activates two incretin receptors at once — GIP and GLP-1. It is a 39-amino-acid acylated peptide with a C20 fatty-diacid chain that binds albumin and gives it a half-life near five days, supporting once-weekly subcutaneous dosing.
The GLP-1 arm enhances glucose-dependent insulin secretion, suppresses glucagon, slows gastric emptying, and reduces appetite centrally. The GIP arm adds further insulinotropic activity and is thought to contribute central effects on appetite and energy balance. Engaging both pathways together produces larger glycemic and weight effects than a GLP-1 receptor agonist alone — a difference borne out when tirzepatide was tested head-to-head against semaglutide.
Main intended effect
Glycemic control in type 2 diabetes and weight reduction in obesity. On the weight side it is currently the most effective single approved agent.
Areas of interest
Type 2 diabetes and obesity are the approved indications. The evidence and label have since extended toward obstructive sleep apnea, with active interest in heart failure with preserved ejection fraction, metabolic liver disease, and kidney outcomes. It is also the active comparator that newer agents (retatrutide, CagriSema) are measured against.
Evidence for intended effects
Tirzepatide has a deep, approval-grade evidence base across two phase 3 programs. In type 2 diabetes, the SURPASS trials showed dose-dependent HbA1c and weight reductions, and SURPASS-2 demonstrated superiority over semaglutide 1 mg head-to-head. In obesity, the SURMOUNT trials showed weight loss up to about 21% at the top dose (SURMOUNT-1), and the SURMOUNT-4 withdrawal trial reached a mean 25.3% with continued treatment — while those switched to placebo regained weight, showing the effect depends on staying on the drug. A SURPASS-4 kidney analysis suggested possible renoprotection that still needs dedicated outcome trials.
| Setting | Strongest evidence | Result |
|---|---|---|
| Type 2 diabetes | SURPASS-2 vs semaglutide (NEJM 2021) | superior HbA1c + weight reduction |
| Obesity | SURMOUNT-1 (NEJM 2022) | up to ~21% weight loss |
| Weight maintenance | SURMOUNT-4 (JAMA 2024) | 25.3% with continued use; regain on stopping |
| Kidney (T2D) | SURPASS-4 analysis (Lancet D&E 2022) | slower eGFR decline (hazard ratio 0.58) |
Studied amounts (literature dosing context)
Tirzepatide is a once-weekly subcutaneous injection, started at 2.5 mg and titrated (5, 10, 15 mg) to limit gastrointestinal effects. Those are the labeled and trial-studied amounts. Because tirzepatide is an approved medicine, dosing should follow the prescribing information and a clinician — this page is reference context, not medical advice.
Safety and regulatory status
Tirzepatide is an approved prescription medicine — cleared in the United States for type 2 diabetes (Mounjaro, 2022) and chronic weight management (Zepbound, 2023), with additional indications following. Its safety profile is the incretin-class norm: dose-dependent, mostly mild-to-moderate gastrointestinal effects (nausea, diarrhea, vomiting, constipation) concentrated during dose escalation, without increased hypoglycemia, plus the class thyroid C-cell boxed warning from rodent data.
As with semaglutide, the platform-specific caution is sourcing: compounded or online "tirzepatide" is not the approved product, and its dose and purity are not assured.
Sources
Tirzepatide, a dual GIP/GLP-1 receptor co-agonist for the treatment of type 2 diabetes
Review (Nauck and D'Alessio, Cardiovascular Diabetology, 2022) summarizing the SURPASS 1–5 phase 3 program, in which once-weekly tirzepatide 5–15 mg reduced HbA1c by about 1.2–2.6% and body weight by 5.4–11.7 kg, with effects generally exceeding selective GLP-1 receptor agonists and basal insulin. It explains tirzepatide as an acylated 39-amino-acid linear peptide engineered as a dual GIP/GLP-1 receptor co-agonist, and reviews the dose-dependent gastrointestinal tolerability profile.
Dose-Dependent Efficacy and Safety of Tirzepatide for Weight Loss in Non-diabetic Adults With Obesity: A Systematic Review and Meta-analysis of Randomized Controlled Trials
Systematic review and meta-analysis in Cureus pooling 4 randomized controlled trials (n=3,553) of tirzepatide in non-diabetic adults with obesity. Tirzepatide produced a mean body weight reduction of 16.54% versus placebo (95% CI −15.59 to −17.48), with a clear dose-response of −0.72% per 1 mg dose increment (p=0.0014); participants were 23-fold more likely to achieve ≥15% weight loss (OR 23.25; 95% CI 18.06–29.94). BMI fell 7.09 kg/m², waist circumference 12.77 cm, and HbA1c 0.42%; quality-of-life scores improved across both SF-36v2 and IWQOL-Lite-CT instruments. Gastrointestinal adverse events were substantially more frequent (nausea OR 4.20, vomiting OR 6.93, diarrhoea OR 3.80) though serious adverse events were comparable to placebo (OR 0.97).
Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1)
Phase 3, double-blind, randomized, placebo-controlled monotherapy trial (Rosenstock and colleagues, The Lancet, 2021) of once-weekly subcutaneous tirzepatide (5, 10, 15 mg) in patients with type 2 diabetes inadequately controlled by diet and exercise. All doses were superior to placebo for reducing HbA1c and body weight, with mild-to-moderate transient gastrointestinal events (nausea 12–18%, diarrhea 12–14%). The trial established tirzepatide — a 39-amino-acid dual GIP/GLP-1 receptor agonist — as effective monotherapy and anchored the SURPASS program.
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes (SURPASS-2)
Phase 3, open-label, randomized 40-week trial (Frías and colleagues, New England Journal of Medicine, 2021) comparing once-weekly subcutaneous tirzepatide (5, 10, or 15 mg) against semaglutide 1 mg in patients with type 2 diabetes on metformin. All tirzepatide doses were superior to semaglutide for reducing HbA1c and produced greater body-weight reductions. The most common adverse events were mild-to-moderate gastrointestinal effects. SURPASS-2 is the key head-to-head establishing tirzepatide's edge over a GLP-1 receptor agonist in type 2 diabetes.
Effects of tirzepatide versus insulin glargine on kidney outcomes in type 2 diabetes (SURPASS-4 post-hoc)
Pre-specified/post-hoc kidney analysis of the SURPASS-4 phase 3 trial (Heerspink and colleagues, The Lancet Diabetes & Endocrinology, 2022) comparing tirzepatide with insulin glargine in people with type 2 diabetes at high cardiovascular risk. Tirzepatide reduced a composite kidney endpoint (hazard ratio 0.58) and slowed the rate of eGFR decline (−1.4 vs −3.6 mL/min/1.73 m² per year) versus glargine, with reduced albuminuria — signals of possible renoprotection that warrant dedicated outcome trials.
Tirzepatide Once Weekly for the Treatment of Obesity
Phase 3 SURMOUNT-1 double-blind RCT (Jastreboff et al., NEJM 2022) enrolling 2,539 adults with BMI ≥30 or ≥27 with weight-related complications but without diabetes; mean baseline weight 104.8 kg, BMI 38.0. Participants received once-weekly subcutaneous tirzepatide 5 mg, 10 mg, or 15 mg, or placebo, for 72 weeks including a 20-week dose-escalation period. Mean weight reductions were −15.0% (5 mg; 95% CI −15.9 to −14.2), −19.5% (10 mg; 95% CI −20.4 to −18.5), and −20.9% (15 mg; 95% CI −21.8 to −19.9) versus −3.1% with placebo (all p<0.001). Weight loss ≥5% was achieved by 85%, 89%, and 91% of the three tirzepatide groups versus 35% with placebo. GI adverse events were most common and generally mild to moderate; discontinuation due to AEs occurred in 4.3%, 7.1%, 6.2%, and 2.6% across groups.
Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2)
Phase 3, double-blind, randomized, placebo-controlled 72-week trial (Garvey and colleagues, The Lancet, 2023) of once-weekly subcutaneous tirzepatide (10 or 15 mg) for weight management in adults with obesity and type 2 diabetes. Tirzepatide produced least-squares mean body-weight reductions of 12.8% (10 mg) and 14.7% (15 mg) versus 3.2% with placebo. The most frequent adverse events were mild-to-moderate gastrointestinal effects that rarely led to discontinuation.
Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity (SURMOUNT-4)
Phase 3 randomized withdrawal trial (Aronne and colleagues, JAMA, 2024) testing whether continuing tirzepatide maintains weight loss. After an open-label lead-in, participants continuing the maximum tolerated dose (10 or 15 mg) reached a mean weight reduction of 25.3% from week 0 to 88, versus 9.9% in those switched to placebo (who regained weight). The result quantifies how much of tirzepatide's weight loss depends on continued treatment. Adverse events were predominantly mild-to-moderate gastrointestinal.
ZEPBOUND (tirzepatide) injection, for subcutaneous use — Prescribing Information
Official FDA-approved prescribing information for Zepbound (tirzepatide injection) for subcutaneous use, approved November 8, 2023. Tirzepatide is a dual GIP and GLP-1 receptor agonist indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index of 30 kg/m² or greater (obesity), or 27 kg/m² or greater (overweight) in the presence of at least one weight-related comorbidity such as hypertension, dyslipidemia, or obstructive sleep apnea. The label carries a boxed warning regarding the risk of thyroid C-cell tumors observed in rodent studies and contraindicates use in patients with a personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2. Clinical evidence is drawn from the SURMOUNT phase 3 program. The label also provides dosing escalation guidance, contraindications, and warnings for pancreatitis, gallbladder disease, and hypoglycemia in combination with insulin or secretagogues.
https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/217806s000lbl.pdf