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Peptide profile · Dual GIP/GLP-1 receptor agonist, 39-amino-acid modified peptide

Tirzepatide

Also known as: Mounjaro, Zepbound, Dual GIP/GLP-1 receptor agonist, LY3298176

An FDA-approved dual GIP and GLP-1 receptor agonist with large randomised trials showing the greatest weight loss of any approved incretin therapy, plus approvals for type 2 diabetes and obstructive sleep apnoea.

Established evidenceFDA-approved for this use
Abstract peptide-chain illustration for the tirzepatide profile

Evidence level

Established

SURPASS (diabetes) and SURMOUNT (obesity) phase 3 programmes; SURMOUNT-1 showed up to ~21% mean weight loss at 72 weeks; SURMOUNT-5 showed superiority to semaglutide 2.4 mg head-to-head; SURPASS-CVOT showed cardiovascular non-inferiority to dulaglutide.

Regulatory status (US)

FDA-approved for this use

FDA-approved for type 2 diabetes (Mounjaro, 2022), chronic weight management (Zepbound, 2023) and moderate-to-severe obstructive sleep apnoea with obesity (Zepbound, December 2024). The FDA declared the tirzepatide shortage resolved in late 2024, ending most compounding.

Mechanism (proposed)

Activates both GIP and GLP-1 receptors, enhancing insulin secretion, suppressing glucagon and appetite, and slowing gastric emptying; the GIP component may add metabolic effects beyond GLP-1 alone.

Studied for: Type 2 diabetes (approved), Chronic weight management (approved), Obstructive sleep apnoea with obesity (approved), Heart failure with preserved EF and obesity (SUMMIT), Cardiovascular outcomes (SURPASS-CVOT)

Full research analysis

GLP-1 Peptides: Established Uses Versus Emerging Research

Semaglutide and tirzepatide are the best-evidenced peptides in medicine — for specific uses. We separate the approved indications with large trials from the emerging research (kidney, liver, heart failure, sleep apnoea, Alzheimer's) and the open questions about regain, muscle loss and compounded products.

Read the analysis

What tirzepatide is

Tirzepatide is a single 39-amino-acid peptide engineered to activate two incretin receptors, GIP and GLP-1. It is approved for type 2 diabetes, chronic weight management and, since late 2024, obstructive sleep apnoea in adults with obesity.

Where the evidence stands

The SURMOUNT-1 trial reported mean weight loss of up to about 21% at the highest dose over 72 weeks[1], the largest seen for an approved incretin drug. SURMOUNT-5 then compared it directly with semaglutide 2.4 mg and found greater weight loss with tirzepatide[2]. SURMOUNT-4 showed what happens on stopping: substantial regain[3]. The evidence for its approved uses is established[4].

Regulatory position

FDA-approved under two brand names for three indications. Compounding of copies, permitted during the shortage, lost that basis when the FDA declared the shortage resolved in late 2024. Counterfeit products remain a documented problem.

Safety summary

Gastrointestinal effects are the most common adverse events; boxed warning for thyroid C-cell tumours (rodent); pancreatitis, gallbladder disease, hypoglycaemia with insulin/sulfonylureas, acute kidney injury from dehydration and hypersensitivity are labelled. Weight regain follows discontinuation (SURMOUNT-4). Compounded and counterfeit products carry additional risks.

Frequently asked questions

How is tirzepatide different from semaglutide?
Tirzepatide activates both GIP and GLP-1 receptors; semaglutide activates GLP-1 only. In a head-to-head trial tirzepatide produced more weight loss (about 20% vs 14% at 72 weeks).
Does the weight come back after stopping tirzepatide?
In SURMOUNT-4, people switched to placebo regained about 14% of body weight over a year while those who continued kept losing.
Is compounded tirzepatide legal?
The FDA declared the tirzepatide shortage resolved in late 2024, which ended the shortage-based allowance for compounding copies. Compounded versions are not FDA-approved.

References

Numbered in order of first use. Study type is shown for every source; see our methodology for how we rank evidence.

  1. 1.

    Jastreboff AM, Aronne LJ, Ahmad NN, et al.. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1) New England Journal of Medicine, 2022.

    Randomized controlled trialAdults with BMI ≥30 (or ≥27 with comorbidity), without diabetesn = 2539

    Result: Mean weight change −15.0% (5 mg), −19.5% (10 mg), −20.9% (15 mg) vs −3.1% placebo at 72 weeks.

    Limitations: 72 weeks; regain after stopping shown in SURMOUNT-4.

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  2. 2.

    Aronne LJ, Horn DB, le Roux CW, et al.. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity (SURMOUNT-5) New England Journal of Medicine, 2025.

    Randomized controlled trialAdults with obesity without diabetesn = 751

    Result: Mean weight change −20.2% with tirzepatide vs −13.7% with semaglutide 2.4 mg at 72 weeks.

    Limitations: Open-label; sponsor-run.

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  3. 3.

    Aronne LJ, Sattar N, Horn DB, et al.. Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity — The SURMOUNT-4 Randomized Clinical Trial JAMA, 2024.

    Randomized controlled trialAdults with obesity after 36-week tirzepatide lead-inn = 670

    Result: Switching to placebo led to ~14% weight regain over 52 weeks vs further ~5.5% loss on continued tirzepatide.

    Limitations: Selected responders entered the randomised phase.

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  4. 4.

    FDA Approves New Medication for Chronic Weight Management U.S. Food and Drug Administration, 2023.

    Regulatory source

    Result: Approval of tirzepatide (Zepbound) for chronic weight management.

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Review status: Editorially reviewed against primary sources. This article was fact-checked against the primary sources listed in the references by our editorial team, and it has not been reviewed by a licensed clinician. It is educational content, not medical advice. Read our editorial policy and methodology. Spotted an error? Tell us.

Profile by Tristen Ta. Published August 15, 2026; updated August 15, 2026.

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