Tirzepatide (MOUNJARO, ZEPBOUND) for Diabetes, Overweight and Obesity

In 2022 the Food and Drug Administration (FDA) approved tirzepatide, marketed as MOUNJARO and administered as a subcutaneous injection, as an adjunct to diet and exercise to improve glycemic control in people with type 2 diabetes. The approval was for adults and children 10 years of age and older.

In 2023 the FDA approved tirzepatide, marketed as ZEPBOUND, for weight management in combination with a reduced-calorie diet and increased physical activity. The approval was for adults with obesity (body mass index [BMI] of at least 30 kilograms per square meter [kg/m]) or with overweight (BMI of at least 27 kg/m) and at least one weight-related comorbid condition, such as hypertension, cardiovascular disease, dyslipidemia (abnormal blood lipid levels) or type 2 diabetes.[1] In 2024 the FDA approved a supplemental indication for Zepbound: to treat moderate to severe obstructive sleep apnea in adults with obesity.[2]

As is the case with semaglutide (WEGOVY), discussed in another article in this issue, tirzepatide has become a widely used medication for both type 2 diabetes and weight management. In early 2025 tirzepatide overtook semaglutide as the most commonly prescribed glucagon-like peptide-1 (GLP-1) drug.[3]

Although tirzepatide is effective in reducing excess body weight and maintaining weight loss, treatment must continue indefinitely and there are important gastrointestinal adverse effects. Moreover, tirzepatide is expensive and its safety beyond several years of use is unknown. The wholesale price for a month’s supply of tirzepatide is $1,086.[4]

Background

Tirzepatide has dual actions. As a GLP-1 agonist, the drug mimics a hormone involved in the metabolism of carbohydrates, including glucose.[5],[6],[7] Tirzepatide is also an insulinotropic polypeptide (GIP) agonist; among other actions, GIPs promote insulin secretion in the body after meals.

There are approximately 38 million adults with type 2 diabetes in the United States,[8] 100 million people with obesity (including 22 million who are severely obese [BMI at least 40 kg/m])[9] and 32 million people with obstructive sleep apnea (an impedance of airflow that disrupts lung function and sleep and that is associated with obesity).[10]

Tirzepatide dosing is similar for diabetes and obesity, with weekly subcutaneous injections starting at 2.5 milligrams (mg) and peaking at 5 to 15 mg.[11],[12] Autoinjector devices (pens) are available to facilitate delivery just below the skin. As of March 2026 the FDA had not approved oral tirzepatide.

Effectiveness of tirzepatide for obesity and overweight

Worst Pills, Best Pills News reviewed tirzepatide for weight loss in October 2023.[13] For obesity and overweight, FDA approval of tirzepatide was based on two randomized, double-blind, placebo-controlled studies in adults.[14] All participants were instructed to reduce food intake by 500 calories per day and increase physical activity to about 150 minutes per week. Weight change was assessed after 72 weeks.

One study enrolled 2,539 individuals who were obese or who were overweight with weight-related conditions, then randomized participants to one of three tirzepatide doses (5, 10 or 15 milligrams [mg] per week) or a placebo. The other study enrolled 938 overweight individuals with type 2 diabetes who were not using insulin and then randomized participants to one of two tirzepatide doses (10 or 15 mg per week) or placebo. These studies showed significant weight reduction in comparison with placebo that correlated with dose and ranged from 10% to 18%.

A third study followed 579 participants with obesity or overweight who were able to decrease their body mass index by at least 5% in 12 weeks with lifestyle interventions only. The participants were then randomized to tirzepatide or placebo for an additional 72 weeks. The tirzepatide group showed markedly greater weight loss.

A fourth study, again of obese or overweight adults with comorbid conditions, randomized 783 individuals who had been using tirzepatide for 36 weeks to continued tirzepatide or placebo. Notably, 14% of participants randomized to tirzepatide withdrew from the trial, often because of adverse effects. During a year of follow-up, participants in the placebo group who remained in the trial regained more than 60% of the weight they had lost.

A 2026 systematic review of 36 randomized trials of GLP-1 drugs, including two tirzepatide trials, estimated that stopping these drugs typically leads to regain of all the weight lost within 1.7 years.[15]

Two randomized placebo-controlled trials supported tirzepatide’s supplemental indication for obstructive sleep apnea in adults with obesity.[16] One trial enrolled 234 participants who were unwilling or unable to use positive airway pressure machines; the other trial enrolled 235 participants using positive airway pressure machines.

After 52 weeks, both studies showed that tirzepatide was associated with substantial improvements over placebo regarding the frequency of apnea (full pauses in breathing) or hypopnea (abnormally slow or shallow breathing) during sleep. Using a continued positive airway pressure machine was associated with slightly greater improvements.

Safety and adverse events

When compared with placebo in clinical trials, tirzepatide significantly increased the risk of gastrointestinal adverse reactions such as nausea, diarrhea, vomiting, constipation, abdominal pain, indigestion and gastroesophageal reflux disease. Nausea and diarrhea were especially common, occurring in 19% to 29% of participants taking tirzepatide, compared with 8% of those receiving placebo. Other adverse effects that were more common with tirzepatide than placebo were hair loss (4-5% versus 1%) and fatigue (5-7% versus 3%). Malnutrition and muscle wasting are also concerns.[17]

Other warnings and precautions in the prescribing information include those for acute pancreatitis, hypersensitivity (for example, anaphylaxis), hypoglycemia, diabetic retinopathy, and pulmonary aspiration during general anesthesia or deep sedation.

Tirzepatide should not be used during pregnancy, because it may harm the fetus. Moreover, because tirzepatide alters digestion and food transit through the gut, women taking oral contraceptives should switch to a non-oral contraceptive method or add a barrier method of contraception for at least four weeks after starting the medicine and for four additional weeks after each increase in dose.

Like semaglutide, tirzepatide carries a boxed warning (the FDA’s most serious warning) for thyroid C-cell tumors and is contraindicated in patients with multiple endocrine neoplasia syndrome type 2.[18]

What You Can Do

Tirzepatide can be effective for type 2 diabetes, for adults with obesity, for adults with overweight and at least one weight-related comorbid condition, and for sleep apnea in adults with obesity. However, tirzepatide is associated with frequent gastrointestinal adverse effects, which lead many people to interrupt or stop treatment and thus lose the benefits of treatment.

Moreover, tirzepatide is used in combination with a reduced-calorie diet and increased physical activity for overweight or obesity. For this reason and because lifestyle interventions are safer and can be effective on their own, they should be tried before starting tirzepatide or another GLP-1 drug. A common-sense diet (for example, small, low-fat, fiber- and protein-sufficient meals) along with resistance and aerobics training to promote weight loss and muscle and bone strength can help to minimize the common gastrointestinal and other adverse effects associated with tirzepatide use.[19]

The FDA first approved tirzepatide in 2022. The drug’s safety for seven years — the time period for which Public Citizen’s Health Research Group typically cautions against using a new drug — is not known.

For chronic weight management, discuss with your clinician the adverse effects of tirzepatide, the likelihood of substantial weight gain if the drug is stopped, and the advantages of trying to lose weight through a reduced-calorie diet and increased physical activity.
 

References

[1] U.S. Food and Drug Administration. NDA 217806 Approval. November 8, 2023.  https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/217806Orig1s000ltr.pdf. Accessed January 29, 2026.

[2] U.S. Food and Drug Administration. NDA 217806 S-013 Supplement Approval. December 20, 2024. https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2024/217806Orig1s013ltr.pdf. Accessed January 1, 2026.

[3] Pequeno IV A. Weight loss drugs now account for 1 in 14 prescriptions, study says. Forbes. January 20, 2026. https://www.forbes.com/sites/antoniopequenoiv/2026/01/20/weight-loss-drugs-now-account-for-1-in-14-prescriptions-study-says/. Accessed January 29, 2026.

[4] Lilly USA. How much should I expect to pay for Zepbound (tirzepatide)? October 2025. https://pricinginfo.lilly.com/zepbound. Accessed January 27, 2026.

[5] Tirzepatide (MOUNJARO): Another diabetes drug seeking FDA approval for weight loss. Worst Pills, Best Pills News. October 2023. https://www.worstpills.org/newsletters/view/1558. Accessed January 29, 2026.

[6] Cleveland Clinic. Glucagon. January 21, 2025. https://my.clevelandclinic.org/health/articles/22283-glucagon. Accessed January 28, 2026.

[7] Dominiczak M. Chapter 31: Glucose Homeostasis and Fuel Metabolism: Diabetes Mellitus. In Medical Biochemistry 6^th Edition. pp. 471-499. Elsevier ClinicalKey Books. DOI: 10.1016/B978-0-323-83450-6.00031-0.

[8] U.S. Centers for Disease Control and Prevention. National diabetes statistics report. January 21, 2026. https://www.cdc.gov/diabetes/php/data-research/index.html. Accessed January 29, 2026.

[9] U.S. Centers for Disease Control and Prevention. Obesity. May 14, 2024.  https://www.cdc.gov/obesity/adult-obesity-facts/index.html. Accessed February 3, 2026.

[10] Sönmez I, Vo Dupuy A, Yu KS, et al. Unmasking obstructive sleep apnea: estimated prevalence and impact in the United States. Respir Med. 2025 Nov;248:108348.

[11] Lilly USA. Label: tirzepatide (ZEPBOUND). January 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/217806s037lbl.pdf. Accessed January 29, 2026.

[12] Lilly USA. Label: tirzepatide (MOUNJARO). January 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/215866s041lbl.pdf. Accessed January 29, 2026.

[13] Tirzepatide (MOUNJARO): Another diabetes drug seeking FDA approval for weight loss. Worst Pills, Best Pills News. October 2023. https://www.worstpills.org/newsletters/view/1558. Access January 29, 2026.

[14] Lilly USA. Label: tirzepatide (ZEPBOUND). January 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/217806s037lbl.pdf. Accessed January 29, 2026.

[15] West S, Scragg J, Aveyard P, et al. Weight regain after cessation of medication for weight management: systematic review and meta-analysis. BMJ. 2026 Jan 7;392:e085304.

[16] Lilly USA. Label: tirzepatide (ZEPBOUND). January 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/217806s037lbl.pdf. Accessed January 29, 2026.

[17] Sanchis-Gomar F, Neeland IJ, Ruiz-Lozano P, et al. Preserving the metabolic engine: muscle as the therapeutic target for cardiovascular prevention in obesity pharmacotherapy. Curr Cardiol Rep. 2025;28(1):2.

[18] Ibid.

[19] Mehrtash F, Dushay J, Manson JE. Integrating diet and physical activity when prescribing GLP-1s—lifestyle factors remain crucial. JAMA Intern Med. 2025 Sep 1;185(9):1151-1152.