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# Tirzepatide

High Evidence 

A dual GIP/GLP-1 receptor agonist FDA-approved for type 2 diabetes, weight management, and MASH with liver fibrosis.

Aliases Mounjaro +1 more 

Evidence High Evidence 

Last Updated  2026-06-30 

Reading Time  4 min 

## Table of Contents

1.  [What It Is](#what-it-is)
2.  [Regulatory Status](#regulatory-status)
3.  [Evidence Snapshot](#evidence-snapshot)
4.  [Commonly Discussed Benefits](#benefits)
5.  [Safety & Cautions](#safety)
6.  [Comparisons](#comparisons)
7.  [Calculator Tools](#calculator)
8.  [Citations](#citations)

## What It Is

Tirzepatide is a first-in-class dual incretin agonist that activates both the GIP and GLP-1 receptors. FDA-approved under the brand names Mounjaro (diabetes) and Zepbound (weight management), it has demonstrated significant weight loss and glycemic control in clinical trials. In 2026, tirzepatide received FDA approval for metabolic dysfunction-associated steatohepatitis (MASH) with liver fibrosis stages F2 or F3 — becoming the second FDA-approved pharmacotherapy for MASH after resmetirom (Rezdiffra). The SYNERGY-NASH Phase 2 trial showed 51.8%, 62.8%, and 73.3% of participants on 5 mg, 10 mg, and 15 mg doses achieved MASH resolution with no worsening of fibrosis at 52 weeks, compared to 13.2% on placebo. Additionally, 59.1%, 53.3%, and 54.2% of participants across doses achieved 1-stage or greater fibrosis improvement without worsening of MASH versus 32.8% on placebo. The FDA granted breakthrough therapy designation for this indication. In a landmark head-to-head trial published in the New England Journal of Medicine (2025), tirzepatide was shown to be superior to semaglutide with respect to body weight reduction: the mean percent change in weight at week 72 was −20.2% with tirzepatide versus −13.7% with semaglutide, with tirzepatide also producing greater waist circumference reductions. The SURMOUNT trial series showed average weight loss of 20–25% of body weight in some cohorts. In the Phase 3 SURMOUNT-OSA trial, tirzepatide demonstrated a reduction of 25.3 to 29.3 events per hour in apnea-hypopnea index versus approximately 5 with placebo, alongside 17–20% body weight reduction — establishing a potential role in treating obesity-related obstructive sleep apnea. Tirzepatide is also in clinical trials for autoimmune conditions in adults with obesity — notably, Phase 3 trials combining tirzepatide with ixekizumab (Taltz) for plaque psoriasis and psoriatic arthritis in patients with obesity are expected to complete in the first half of 2026. Mounjaro is under FDA review for a new indication to reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes, with a decision expected in early-to-mid 2026. Tirzepatide monotherapy is also in clinical trials for type 1 diabetes (estimated completion 2027). The Phase 3 SUMMIT trial demonstrated that tirzepatide reduced the composite risk of cardiovascular death or worsening heart failure by 38% in adults with heart failure with preserved ejection fraction (HFpEF) and obesity over a median follow-up of approximately 2 years. Participants showed significant improvements in physical function, exercise tolerance, weight loss, and reduced systemic inflammation. While tirzepatide is not yet FDA-approved for HFpEF, these results position it as a potential first incretin therapy for obesity-related heart failure, with regulatory submission anticipated. A May 2026 meta-analysis of over 90,000 participants across multiple GLP-1 RA clinical trials confirmed that the GLP-1 receptor agonist class — including both semaglutide and tirzepatide — significantly reduces cardiovascular events including heart attacks, strokes, and heart failure hospitalization, further reinforcing the cardiometabolic benefits of incretin-based therapies. The Medicare GLP-1 Bridge program, launching July 1, 2026, covers Zepbound (KwikPen) for eligible Medicare Part D beneficiaries at a $50/month copayment — representing a major access expansion for one of the most effective obesity treatments available. The program runs through December 31, 2027, and is administered outside the standard Part D benefit, meaning copayments remain flat at $50 regardless of benefit phase. Alongside Foundayo and Wegovy, Zepbound is one of only three medications designated by CMS for the bridge program.

Also known as:  Mounjaro, Zepbound 

## Regulatory Status

FDA-Approved (T2D, obesity, MASH) 

FDA-approved as Mounjaro for type 2 diabetes (May 2022), as Zepbound for chronic weight management (November 2023), and for MASH with moderate-to-advanced fibrosis (early 2026). 73.3% of patients taking 15 mg achieved MASH resolution at 52 weeks in SYNERGY-NASH. SUMMIT trial for HFpEF with obesity submission anticipated.

Effective: 2026

[View FDA Source](https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-was-superior-placebo-mash-resolution-and-more)

## Evidence Snapshot

High Evidence 

Low 

Medium 

High 

Study Type

Model

Outcome

Link

Phase 3 (SURMOUNT)

Dual GIP/GLP-1 agonist

Average weight loss of 20-25% of body weight

[Source](https://pubmed.ncbi.nlm.nih.gov/35658024/)

Phase 3 (SURMOUNT-5)

Tirzepatide vs semaglutide head-to-head

Statistically superior weight loss vs semaglutide 2.4mg

[Source](https://pubmed.ncbi.nlm.nih.gov/)

Phase 3 (SURMOUNT-OSA)

Tirzepatide in obesity-related OSA

25.3–29.3 AHI reduction vs ~5 placebo; 17–20% weight loss

[Source](https://www.nejm.org/doi/full/10.1056/NEJMoa2404881)

Phase 3 (NEJM 2025)

Tirzepatide vs semaglutide head-to-head, 72 weeks

−20.2% weight loss (tirzepatide) vs −13.7% (semaglutide); superior waist circumference reduction

[Source](https://www.nejm.org/doi/full/10.1056/NEJMoa2416394)

Phase 2 (SYNERGY-NASH)

Tirzepatide 5/10/15 mg vs placebo in MASH with fibrosis F2-F3, 52 weeks

73.3% MASH resolution at 15 mg vs 13.2% placebo; 54.2% achieved ≥1-stage fibrosis improvement without worsening of MASH; led to FDA breakthrough therapy designation and 2026 MASH approval

[Source](https://www.nejm.org/doi/abs/10.1056/NEJMoa2401943)

Phase 3 (SUMMIT)

Tirzepatide in HFpEF with obesity (n=731), median ~2 years follow-up

38% reduction in cardiovascular death or worsening heart failure; improved exercise tolerance and physical function; significant weight loss and reduced inflammation

[Source](https://www.nature.com/articles/s41591-024-03374-z)

## Commonly Discussed Benefits

[Weight Management](/benefits/weight-management)[Appetite Regulation](/benefits/appetite-regulation)[Metabolism](/benefits/metabolism)[Fat Loss](/benefits/fat-loss)[Cardiovascular](/benefits/cardiovascular)

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## Safety & Cautions

-   FDA-approved prescription medication requiring medical supervision
-   Common side effects include nausea, diarrhea, and decreased appetite
-   Contraindicated in patients with personal/family history of medullary thyroid carcinoma
-   Not for use with other GLP-1 receptor agonists
-   On May 1, 2026, the FDA proposed excluding tirzepatide (along with semaglutide and liraglutide) from the 503B Bulks List. Public comment period closes June 29, 2026.
-   Medicare GLP-1 Bridge launches July 1, 2026: eligible Part D beneficiaries can access Zepbound (KwikPen) at $50/month through December 31, 2027

## Comparisons

See how Tirzepatide compares to related peptides:

[Tirzepatide vs Cagrilintide](/compare/tirzepatide-vs-cagrilintide) [Tirzepatide vs CagriSema](/compare/tirzepatide-vs-cagrisema) [Tirzepatide vs CT-388](/compare/tirzepatide-vs-ct-388) [Tirzepatide vs Efocipegtrutide](/compare/tirzepatide-vs-efocipegtrutide) [Tirzepatide vs Efpeglenatide](/compare/tirzepatide-vs-efpeglenatide) [Tirzepatide vs Efruxifermin](/compare/tirzepatide-vs-efruxifermin) [Tirzepatide vs Glepaglutide](/compare/tirzepatide-vs-glepaglutide) [Tirzepatide vs Insulin Efsitora Alfa](/compare/tirzepatide-vs-insulin-efsitora-alfa) [Tirzepatide vs Maridebart Cafraglutide (MariTide)](/compare/tirzepatide-vs-maridebart-cafraglutide) [Tirzepatide vs MariTide](/compare/tirzepatide-vs-maritide) [Tirzepatide vs Mazdutide](/compare/tirzepatide-vs-mazdutide) [Tirzepatide vs NA-931 (Bioglutide)](/compare/tirzepatide-vs-na-931) [Tirzepatide vs Pegozafermin](/compare/tirzepatide-vs-pegozafermin) [Tirzepatide vs Retatrutide](/compare/tirzepatide-vs-retatrutide) [Tirzepatide vs Ribupatide](/compare/tirzepatide-vs-ribupatide) [Tirzepatide vs Semaglutide](/compare/tirzepatide-vs-semaglutide) [Tirzepatide vs Survodutide](/compare/tirzepatide-vs-survodutide) [Tirzepatide vs UBT251](/compare/tirzepatide-vs-ubt251) [Tirzepatide vs WVE-007](/compare/tirzepatide-vs-wve-007)

## Calculator Tools

Use our research tools to explore dosing and reconstitution data:

[Reconstitution Calculator](/calculators)

## Citations

1.  \[1\]  Jastreboff AM. et al. — Tirzepatide once weekly for the treatment of obesity. N Engl J Med. 2022 [PubMed](https://pubmed.ncbi.nlm.nih.gov/35658024/)
2.  \[2\]  Genetic predictors of GLP1 receptor agonist weight loss and side effects — Nature 2026 [PubMed](https://www.nature.com/articles/s41586-026-10330-z)
3.  \[3\]  Tirzepatide as Compared with Semaglutide for the Treatment of Obesity — NEJM 2025 [PubMed](https://www.nejm.org/doi/full/10.1056/NEJMoa2416394)
4.  \[4\]  FDA Proposes to Exclude Semaglutide, Tirzepatide, and Liraglutide on 503B Bulks List — FDA. May 2026 [PubMed](https://www.fda.gov/news-events/press-announcements/fda-proposes-exclude-semaglutide-tirzepatide-and-liraglutide-503b-bulks-list)
5.  \[5\]  Tirzepatide for Metabolic Dysfunction–Associated Steatohepatitis with Liver Fibrosis — NEJM 2024 [PubMed](https://www.nejm.org/doi/abs/10.1056/NEJMoa2401943)
6.  \[6\]  Eli Lilly — SYNERGY-NASH Phase 2 results: MASH resolution and fibrosis improvement [PubMed](https://investor.lilly.com/news-releases/news-release-details/lillys-tirzepatide-was-superior-placebo-mash-resolution-and-more)
7.  \[7\]  SUMMIT Trial -- Effects of tirzepatide on heart failure with preserved ejection fraction and obesity. Nature Medicine, 2024 [PubMed](https://www.nature.com/articles/s41591-024-03374-z)
8.  \[8\]  CMS — Medicare GLP-1 Bridge: $50/month Zepbound coverage for Medicare Part D beneficiaries beginning July 1, 2026 [PubMed](https://www.cms.gov/medicare/coverage/prescription-drug-coverage/medicare-glp-1-bridge)

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## Related Peptides

### Cagrilintide

High Evidence 

A long-acting amylin analog studied for appetite regulation; NDA filed for CagriSema (cagrilintide + semaglutide) combination in December 2025, with FDA review expected in 2026.

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### CT-388

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### Efocipegtrutide

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### Pegozafermin

Low Evidence 

Pegozafermin (development code BIO89-100) is an investigational, long-acting analog of fibroblast growth factor 21 (FGF21) being developed for metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) and for severe hypertriglyceridemia (SHTG). Originally developed by 89bio and acquired by Roche in a deal announced in September 2025 (about $2.4 billion upfront and up to roughly $3.5 billion including a contingent value right), it uses site-specific glycoPEGylation to extend the very short half-life of native FGF21 to roughly 55-100 hours, enabling once-weekly or once-every-two-weeks subcutaneous dosing. FGF21 is a metabolic hormone that acts on liver, fat, and other tissues to improve insulin sensitivity, lower triglycerides, and exert direct anti-fibrotic and anti-inflammatory effects. In the Phase 2b ENLIVEN trial in biopsy-confirmed F2-F3 MASH, the 44 mg every-two-weeks dose produced at least a one-stage fibrosis improvement without worsening of MASH in about 27% of patients versus 7% on placebo, and MASH resolution without worsening of fibrosis in about 26% versus 2% on placebo, with benefits sustained through week 48. Pegozafermin holds FDA Breakthrough Therapy designation and EMA PRIME status for MASH and has advanced into the Phase 3 ENLIGHTEN program (ENLIGHTEN-Fibrosis in non-cirrhotic F2-F3 MASH and ENLIGHTEN-Cirrhosis in compensated F4 cirrhosis), plus the Phase 3 ENTRUST trial in SHTG.

[metabolic dysfunction-associated steatohepatitis (MASH/NASH) - fibrosis improvement, MASH resolution, and reduced liver fat (investigational)](</benefits/metabolic dysfunction-associated steatohepatitis \(MASH/NASH\) - fibrosis improvement, MASH resolution, and reduced liver fat \(investigational\)>)[severe hypertriglyceridemia (SHTG) - large reductions in blood triglycerides (investigational; Phase 3 ENTRUST)](</benefits/severe hypertriglyceridemia \(SHTG\) - large reductions in blood triglycerides \(investigational; Phase 3 ENTRUST\)>)[improved insulin sensitivity and glycemic markers](</benefits/improved insulin sensitivity and glycemic markers>)[improvements in non-invasive markers of liver injury and fibrosis (liver fat by MRI-PDFF, liver enzymes, fibrosis biomarkers)](</benefits/improvements in non-invasive markers of liver injury and fibrosis \(liver fat by MRI-PDFF, liver enzymes, fibrosis biomarkers\)>)+1 more 

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### Retatrutide

High Evidence 

An investigational triple agonist (GIP/GLP-1/glucagon) studied for obesity and metabolic disease.

[Weight Management](/benefits/weight-management)[Appetite Regulation](/benefits/appetite-regulation)[Metabolism](/benefits/metabolism)[Fat Loss](/benefits/fat-loss)

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### Ribupatide

Medium Evidence 

A once-weekly injectable GLP-1/GIP dual receptor agonist in Phase 3 trials for obesity, with an oral formulation in development and backed by a record-setting $625M biotech IPO.

[Weight Management](/benefits/weight-management)[Appetite Regulation](/benefits/appetite-regulation)[Metabolism](/benefits/metabolism)[Fat Loss](/benefits/fat-loss)

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### Semaglutide

High Evidence 

A GLP-1 receptor agonist FDA-approved for type 2 diabetes and chronic weight management.

[Weight Management](/benefits/weight-management)[Appetite Regulation](/benefits/appetite-regulation)[Metabolism](/benefits/metabolism)[Fat Loss](/benefits/fat-loss)+3 more 

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### Survodutide

Medium Evidence 

A dual GLP-1/glucagon receptor agonist with FDA Breakthrough Therapy designation for MASH and Priority Review NDA filed February 2026. Phase 3 SYNCHRONIZE-1 reported 16.6% weight loss at 76 weeks; approval possible Q3 2026.

[Weight Management](/benefits/weight-management)[Appetite Regulation](/benefits/appetite-regulation)[Metabolism](/benefits/metabolism)[Fat Loss](/benefits/fat-loss)

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### UBT251

Medium Evidence 

A GLP-1/GIP/glucagon triple receptor agonist in Phase 2 development for type 2 diabetes and obesity, competing with retatrutide in the triple-agonist space.

[Weight Management](/benefits/weight-management)[Fat Loss](/benefits/fat-loss)[Metabolism](/benefits/metabolism)[Appetite Regulation](/benefits/appetite-regulation)

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### WVE-007

Low Evidence 

WVE-007 is Wave Life Sciences' investigational GalNAc-conjugated siRNA that silences the liver gene INHBE to lower the hepatokine Activin E, aiming to produce muscle-sparing fat loss. In the Phase 1 INLIGHT trial a single subcutaneous dose reduced visceral and total fat while preserving or increasing lean mass, with durable target knockdown that could support once- or twice-yearly dosing.

[Weight Management](/benefits/weight-management)[Metabolism](/benefits/metabolism)[Fat Loss](/benefits/fat-loss)[muscle-preservation](/benefits/muscle-preservation)

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