# Tirzepatide

- Canonical: https://residue.info/c/tirzepatide/
- Also called: LY3298176, Mounjaro, Zepbound
- Evidence grade: A (Approved / regulatory-grade). FDA-approved for type 2 diabetes (Mounjaro) and for chronic weight management and obstructive sleep apnea with obesity (Zepbound).
- Status: FDA-approved — Mounjaro (2022), Zepbound (2023)
- PubChem CID: 166567236
- Updated: 2026-10-19 · Reviewed by: Residue Editorial Team

Tirzepatide is a once-weekly peptide that activates GIP and GLP-1 receptors. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for weight management and obstructive sleep apnea in adults with obesity [1][2]. In SURMOUNT-1, adults with obesity lost 15.0–20.9% of body weight at 72 weeks versus 3.1% on placebo [3]. Its half-life is about five days [4].

## Key findings
- In SURMOUNT-1 (obesity, no diabetes), 72-week weight change was −15.0%, −19.5% and −20.9% at 5, 10 and 15 mg, versus −3.1% with placebo; 57% of the 15 mg group lost 20% or more [3]. (anchor: https://residue.info/c/tirzepatide/#kf-pmid-35658024)
- In SURMOUNT-5, the only head-to-head obesity trial, tirzepatide produced −20.2% versus −13.7% with semaglutide at 72 weeks [5]. (anchor: https://residue.info/c/tirzepatide/#kf-pmid-40353578)
- In SURPASS-2 (type 2 diabetes), all three doses lowered HbA1c more than semaglutide 1 mg (−2.01 to −2.30 vs −1.86 points) [6]. (anchor: https://residue.info/c/tirzepatide/#kf-pmid-34170647)
- In people with obesity and prediabetes treated for three years, 1.3% developed type 2 diabetes on tirzepatide versus 13.3% on placebo [7]. (anchor: https://residue.info/c/tirzepatide/#kf-pmid-39536238)
- Stopping treatment led to regain: after a 36-week lead-in, participants switched to placebo regained 14.0% while those who continued lost a further 5.5% [8]. (anchor: https://residue.info/c/tirzepatide/#kf-pmid-38078870)

## Effects by system
- Body weight (grade A): Chronic weight management in adults with obesity, or overweight with a comorbidity, is an approved indication [2]; −20.9% at 72 weeks with 15 mg in SURMOUNT-1 [3]. (anchor: https://residue.info/c/tirzepatide/#effect-body-weight)
- Glycemic control (grade A): Approved to improve glycemic control in type 2 diabetes [1]; HbA1c −1.87 to −2.07 points at 40 weeks as monotherapy [9]. (anchor: https://residue.info/c/tirzepatide/#effect-glycemic-control)
- Sleep apnea (grade A): Approved for moderate-to-severe OSA in adults with obesity [2]; AHI fell by 25.3–29.3 events/hour versus about 5 on placebo [10]. (anchor: https://residue.info/c/tirzepatide/#effect-sleep-apnea)
- Cardiovascular (grade A): Mounjaro's label includes reducing major adverse cardiovascular events in adults with type 2 diabetes at high risk [1]. (anchor: https://residue.info/c/tirzepatide/#effect-cardiovascular)
- Diabetes prevention (grade B): Progression to type 2 diabetes 1.3% versus 13.3% over 176 weeks in prediabetes (hazard ratio 0.07) [7]. (anchor: https://residue.info/c/tirzepatide/#effect-diabetes-prevention)
- Gastrointestinal (adverse) (grade A): Nausea 12–24%, diarrhea 12–22% and vomiting 2–13% across SURPASS-1 to -5, mostly transient and mild to moderate [11]. (anchor: https://residue.info/c/tirzepatide/#effect-gastrointestinal-adverse)

## How does Tirzepatide work?

Tirzepatide is a single synthetic peptide engineered to act on two incretin receptors: the glucose-dependent insulinotropic polypeptide (GIP) receptor and the glucagon-like peptide-1 (GLP-1) receptor. FDA labeling describes both Mounjaro and Zepbound as GIP receptor and GLP-1 receptor agonists [1][2]. GIP and GLP-1 are both incretins — gut hormones that amplify insulin secretion after a meal — which is why the program was first developed for type 2 diabetes [9].

A population pharmacokinetic model pooled from 19 studies described a two-compartment profile with a half-life of about five days, enabling once-weekly dosing; covariate analysis suggested dose adjustment by demographic subgroup was unnecessary [4].

## What did the SURPASS trials find in type 2 diabetes?

SURPASS-1 randomized 478 adults with type 2 diabetes managed by diet and exercise alone. At 40 weeks, HbA1c fell by 1.87, 1.89 and 2.07 percentage points with 5, 10 and 15 mg, against a rise of 0.04 with placebo; 31–52% of tirzepatide participants reached an HbA1c below 5.7%, versus 1% on placebo [9].

SURPASS-2 then compared tirzepatide with the active comparator semaglutide 1 mg in an open-label 40-week trial of 1,879 patients (mean baseline HbA1c 8.28%). All tirzepatide doses were non-inferior and superior on HbA1c (−2.01, −2.24 and −2.30 points versus −1.86), and weight fell 1.9 to 5.5 kg more than with semaglutide [6]. Hypoglycemia below 54 mg/dL occurred in 0.2–1.7% of tirzepatide participants and 0.4% with semaglutide.

## What did the SURMOUNT trials find in obesity?

SURMOUNT-1 enrolled adults with obesity, or overweight with a weight-related condition, without diabetes; mean baseline weight was 104.8 kg. Mean weight change at 72 weeks was −15.0% (5 mg), −19.5% (10 mg) and −20.9% (15 mg) against −3.1% with placebo, and half or more of the 10 and 15 mg groups lost at least 20% [3]. The prediabetes subgroup continued to 176 weeks, with weight change of −12.3% to −19.7% versus −1.3% and a hazard ratio of 0.07 for progression to type 2 diabetes [7].

SURMOUNT-4 tested what happens after weight loss. All participants took tirzepatide for 36 weeks (mean −20.9%), then were randomized to continue or switch to placebo. From week 36 to 88, the continued group lost a further 5.5% while the placebo group regained 14.0%; 89.5% of those continuing kept at least 80% of their lead-in loss, versus 16.6% on placebo [8].

SURMOUNT-OSA ran two 52-week trials in people with moderate-to-severe obstructive sleep apnea and obesity. The apnea–hypopnea index fell by 25.3 and 29.3 events per hour with tirzepatide against 5.3 and 5.5 with placebo, with improvements in hypoxic burden, hsCRP and systolic blood pressure [10].

SURMOUNT-5 is the first randomized head-to-head obesity trial against semaglutide. In 751 adults without diabetes, weight change at 72 weeks was −20.2% with tirzepatide and −13.7% with semaglutide; waist circumference fell 18.4 cm versus 13.0 cm [5].

## What adverse events were reported in trials?

The dominant adverse events are gastrointestinal and cluster during dose escalation. Pooling SURPASS-1 to -5 (6,263 participants), nausea was reported in 12–24%, diarrhea in 12–22% and vomiting in 2–13%; the events were transient and mild to moderate. Weight loss was similar whether or not participants reported nausea, vomiting or diarrhea, and mediation analysis attributed under 6% of the weight difference versus comparators to these effects [11].

In SURMOUNT-1, adverse events led to treatment discontinuation in 4.3% (5 mg), 7.1% (10 mg) and 6.2% (15 mg) of participants versus 2.6% with placebo [3]. The FDA label carries the full list of warnings and should be read for any clinical question [2].

Two branded products contain tirzepatide: Mounjaro, approved in May 2022 [12], and Zepbound, approved in November 2023 [13]. Zepbound's labeling advises against co-administration with other tirzepatide-containing products or any GLP-1 receptor agonist [2].

During the 2022–2024 shortage, compounded tirzepatide was widely sold. FDA has since declared the shortage resolved; its April 2026 statement says tirzepatide is not on the 503B bulks list or the drug-shortage list, which limits outsourcing-facility compounding, and restates the "essentially a copy" limits for 503A pharmacies [14].

## What is still unknown?

- **Cardiovascular outcomes in obesity without diabetes.** The label's cardiovascular indication is for type 2 diabetes [1]; trial registries list further outcome studies [15].
- **Maintenance.** SURMOUNT-4 shows regain after withdrawal [8]; the best long-term strategy is still being studied.

## Frequently asked questions
**What is tirzepatide approved for?**
As Mounjaro: glycemic control in type 2 diabetes (adults and children 10 and older) and reducing major cardiovascular events in adults with type 2 diabetes at high risk [1]. As Zepbound: chronic weight management in adults with obesity or overweight with a weight-related condition, and moderate-to-severe obstructive sleep apnea in adults with obesity [2].

**What are the most common side effects of tirzepatide?**
Gastrointestinal events. Across the SURPASS trials, nausea occurred in 12–24%, diarrhea in 12–22% and vomiting in 2–13% of participants, mostly transient and mild to moderate [11]. In SURMOUNT-1, adverse events led to discontinuation in 4.3–7.1% on tirzepatide versus 2.6% on placebo [3].

**What is the half-life of tirzepatide?**
About five days, according to a population pharmacokinetic model built from 19 pooled studies [4].

**Is tirzepatide better than semaglutide?**
For weight in adults with obesity without diabetes, SURMOUNT-5 found greater reduction with tirzepatide (−20.2% vs −13.7% at 72 weeks) [5]. In type 2 diabetes, SURPASS-2 found larger HbA1c and weight reductions than semaglutide 1 mg [6]. Semaglutide has a dedicated cardiovascular-outcomes trial in people without diabetes [16]. See the full comparison.

**What happens when tirzepatide is stopped?**
In SURMOUNT-4, participants switched to placebo after 36 weeks regained 14.0% of body weight by week 88, while those who continued lost a further 5.5% [8].

**Can tirzepatide still be compounded?**
FDA declared the tirzepatide shortage resolved, and its April 2026 statement notes tirzepatide is not on the 503B bulks list or the drug-shortage list, which restricts outsourcing-facility compounding [14].

**What is tirzepatide?**
Tirzepatide is a once-weekly peptide that activates both GIP and GLP-1 receptors. It is FDA-approved as Mounjaro for type 2 diabetes and as Zepbound for weight management and obstructive sleep apnea with obesity [1][2].


## Sources
[1] MOUNJARO, MOUNJARO KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-27. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0
[2] ZEPBOUND, ZEPBOUND KWIKPEN prescribing information: Indications and Usage. FDA-approved labeling via openFDA/DailyMed, version effective 2026-08-28. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
[3] Tirzepatide Once Weekly for the Treatment of Obesity. Jastreboff AM et al. N Engl J Med. 2022. https://pubmed.ncbi.nlm.nih.gov/35658024/
[4] Population pharmacokinetics of the GIP/GLP receptor agonist tirzepatide. Schneck K & Urva S CPT Pharmacometrics Syst Pharmacol. 2024. https://pubmed.ncbi.nlm.nih.gov/38356317/
[5] Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. Aronne LJ et al. N Engl J Med. 2025. https://pubmed.ncbi.nlm.nih.gov/40353578/
[6] Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. Frías JP et al. N Engl J Med. 2021. https://pubmed.ncbi.nlm.nih.gov/34170647/
[7] Tirzepatide for Obesity Treatment and Diabetes Prevention. Jastreboff AM et al. N Engl J Med. 2025. https://pubmed.ncbi.nlm.nih.gov/39536238/
[8] Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity: The SURMOUNT-4 Randomized Clinical Trial. Aronne LJ et al. JAMA. 2024. https://pubmed.ncbi.nlm.nih.gov/38078870/
[9] Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Rosenstock J et al. Lancet. 2021. https://pubmed.ncbi.nlm.nih.gov/34186022/
[10] Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity. Malhotra A et al. N Engl J Med. 2024. https://pubmed.ncbi.nlm.nih.gov/38912654/
[11] Gastrointestinal adverse events and weight reduction in people with type 2 diabetes treated with tirzepatide in the SURPASS clinical trials. Patel H et al. Diabetes Obes Metab. 2024. https://pubmed.ncbi.nlm.nih.gov/37853960/
[12] Drugs@FDA: MOUNJARO, MOUNJARO KWIKPEN, MOUNJARO (AUTOINJECTOR) (NDA215866). ELI LILLY AND CO; original approval 2022-05-13; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=215866
[13] Drugs@FDA: ZEPBOUND, ZEPBOUND KWIKPEN, ZEPBOUND (AUTOINJECTOR) (NDA217806). ELI LILLY AND CO; original approval 2023-11-08; Prescription. https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=217806
[14] FDA clarifies policies for compounders as national GLP-1 supply begins to stabilize. U.S. FDA, content current as of 04/01/2026. https://www.fda.gov/drugs/drug-alerts-and-statements/fda-clarifies-policies-compounders-national-glp-1-supply-begins-stabilize
[15] ClinicalTrials.gov registry search: tirzepatide OR LY3298176. 300 registered studies at fetch. https://clinicaltrials.gov/search?intr=tirzepatide%20OR%20LY3298176
[16] Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. Lincoff AM et al. N Engl J Med. 2023. https://pubmed.ncbi.nlm.nih.gov/37952131/

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