tirzepatide (Mounjaro, Zepbound)
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Indications
- treatment of diabetes mellitus type-2 (FDA-approved May 2022)[3]
- useful as adjunct to insulin glargine in patients with type 2 diabetes with inadequate glycemic control[2]
- weight reduction in obese patients with or without type 2 diabetes*[4][5][8]
- reduces blood pressure & weight within 9 months[13]
* weight reductions at 15 mg week approach those of bariatric surgery[8]
Contraindications
- gastroparesis[7]
- personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type-2
Dosage
- weekly subcutaneous injections
- initiate at 2.5 mg SQ, escalate to 5, 7.5, 10, 12.5 or 15 mg SQ weekly every 4 weeks
* if 1 or 2 consecutive doses are missed, resume at last administered dose
* if >= 3 consecutive doses are missed, restart dose escalation starting at 5 mg
Adverse effects
- diarrhea (12-21% vs 10% for placebo), constipation
- nausea (13% vs 3% for placebo), vomiting
- abdominal pain, dyspepsia, eructation, gastroesophageal reflux disease
- injection site reactions, hypersensitivity reactions,
- fatigue, hair loss,
Drug interactions
- may interfere with absorption & activity of oral contraceptives[9]
- drug interaction(s) of acetaminophen in combination with GLP1-agonist
- drug interaction(s) of fluoroquinolones with hypoglycemic agents
Mechanism of action
- dual GLP-1 receptor agonist & GIP receptor agonist
- lowers HgbA1c by 2% when added to glargine
- promotes weight reduction 7-9 kg (from baseline of 86 kg)[1]
- lowers serum triglycerides, LDL cholesterol, & VLDL cholesterol in patients with diabetes mellitus type 2[6]
- weight reduction of 21% at 36 weeks with 10 or 15 mg of tirzepatide[11]
- withdrawal of tirzepatide results in regain of lost weight; continued treatment maintains & continues weight reduction[11]
Clinical trials
- SURMOUNT-1: effective for weight reduction in obese[4]
Notes
- likely to be expensive
- tirzepatide is most effective GLP-1 agonist for both glycemic control & weight loss[14]
More general terms
References
- ↑ 1.0 1.1 Rosenstock J, Wysham C, Frias JP, et al. 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. Lancet 2021 Jun 25; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34186022 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01324-6/fulltext
Frias JP, Davies MJ, Rosenstock J et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med 2021 Jun 25; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/34170647 https://www.nejm.org/doi/10.1056/NEJMoa2107519 - ↑ 2.0 2.1 Dahl D, Onishi Y, Norwood P et al Effect of Subcutaneous Tirzepatide vs Placebo Added to Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes. The SURPASS-5 Randomized Clinical Trial. JAMA. 2022;327(6):534-545 PMID: https://www.ncbi.nlm.nih.gov/pubmed/35133415 https://jamanetwork.com/journals/jama/fullarticle/2788781
- ↑ 3.0 3.1 Zoler ML 'Twincretin' Tirzepatide Gets FDA Approval for Type 2 Diabetes. Medscape. May 13, 2022 https://www.medscape.com/viewarticle/974013
- ↑ 4.0 4.1 4.2 Zoler ML Tirzepatide Powers 'Unprecedented' Weight Loss in Obesity Trial. Medcape. June 4, 2022 https://www.medscape.com/viewarticle/975061
Monaco K Tirzepatide Serves Up Major Weight-Loss Win in Patients With Obesity. SURMOUNT-1 trial tested GIP/GLP-1 receptor agonist in people without diabetes. MedPage Today June 5, 2022 https://www.medpagetoday.com/meetingcoverage/ada/99060
McCall B 'Staggering' Weight Loss and Benefits in Body Composition With Tirzepatide. Medscape. May 19, 2023 https://www.medscape.com/viewarticle/992211 - ↑ 5.0 5.1 Busko M Tirzepatide Lowers Weight Across All Groups With Obesity. Medscape. November 07, 2022 https://www.medscape.com/viewarticle/983672
- ↑ 6.0 6.1 Zoler ML Tirzepatide's Benefits Expand: Lean Mass Up, Serum Lipids Down. Medscape. Oct 14, 2022 https://www.medscape.com/viewarticle/982467
- ↑ 7.0 7.1 NEJM Knowledge+ Endocrinology
- ↑ 8.0 8.1 8.2 Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022 Jul 21; 387:205. PMID: https://www.ncbi.nlm.nih.gov/pubmed/35658024 https://www.nejm.org/doi/10.1056/NEJMoa2206038
Garvey WT et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): A double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2023 Jun 26; [e-pub]. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37385275 https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(23)01200-X/fulltext - ↑ 9.0 9.1 Scherer L Caution Urged for Obesity Drugs and Birth Control Pills. Medscape. Oct 19, 2023 https://www.medscape.com/s/viewarticle/997498
- ↑ Abbasi J FDA Green-Lights Tirzepatide, Marketed as Zepbound, for Chronic Weight Management JAMA. Published online November 15, 2023. PMID: https://www.ncbi.nlm.nih.gov/pubmed/37966831
- ↑ 11.0 11.1 11.2 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. Published online December 11, 2023 PMID: https://www.ncbi.nlm.nih.gov/pubmed/38078870 https://jamanetwork.com/journals/jama/fullarticle/2812936
- ↑ Tchang B How to Prescribe Zepbound. Medscape. Dec 12, 2023 https://www.medscape.com/viewarticle/999162
- ↑ 13.0 13.1 de Lemos JA, Linetzky B, le Roux CW et al Tirzepatide Reduces 24-Hour Ambulatory Blood Pressure in Adults With Body Mass Index >= 27 kg/m2: SURMOUNT-1 Ambulatory Blood Pressure Monitoring Substudy. Hypertension. 2024 Feb 5. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38314555
- ↑ 14.0 14.1 Yao H et al. Comparative effectiveness of GLP-1 receptor agonists on glycaemic control, body weight, and lipid profile for type 2 diabetes: Systematic review and network meta-analysis. BMJ 2024 Jan 29; 384:e076410. PMID: https://www.ncbi.nlm.nih.gov/pubmed/38286487 PMCID: PMC10823535 Free PMC article https://www.bmj.com/content/384/bmj-2023-076410
- ↑ Highlights of Prescribing Information Mounjaro (tirzepatide) injection for subcutaneous use https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/215866s000lbl.pdf