Tirzepatide

Summary

Tirzepatide (brand name Mounjaro for T2DM; Zepbound for obesity) is a once-weekly subcutaneous injectable dual GIP/GLP-1 receptor agonist developed by Eli Lilly. It is FDA-approved for type 2 diabetes mellitus and chronic weight management. Clinical trials (SURPASS, SURMOUNT series) demonstrated superior HbA1c reductions and weight loss compared to semaglutide and other agents.

Mechanism of Action

Tirzepatide is a synthetic peptide that acts as a dual agonist at both glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. It stimulates insulin secretion in a glucose-dependent manner, suppresses glucagon, slows gastric emptying, and reduces appetite and food intake, leading to improved glycemic control and significant weight reduction.

Routes of Administration

Goals & Uses

• Cardiovascular risk reductionCardiovascularModerate
• Non-alcoholic fatty liver disease (MASH/NASH)Hepatic / MetabolicModerate
• Reduction of obstructive sleep apnea severityPulmonary / SleepModerate
• Appetite suppression and satietyNeurological / BehavioralHigh
• Weight loss / obesity managementMetabolicHigh
• Glycemic control in type 2 diabetesMetabolicHigh

Contraindications

• Personal or family history of medullary thyroid carcinoma (MTC)OncologicHigh
• Multiple endocrine neoplasia syndrome type 2 (MEN2)OncologicHigh
• Type 1 diabetes mellitusEndocrineHigh
• Hypersensitivity to tirzepatide or excipientsImmunologicalHigh

Adverse Effects

• PancreatitisGastrointestinalRareInflammation of the pancreas
• HypoglycemiaMetabolicUncommonAbnormally low blood glucose
• Injection site reactionsLocalCommon
• NauseaGastrointestinalCommonFeeling of sickness or urge to vomit
• VomitingGastrointestinalCommonForceful expulsion of stomach contents
• DiarrheaGastrointestinalCommonLoose or frequent stools

Drug Interactions

• Insulin and insulin secretagogues (e.g., sulfonylureas)High
• Oral contraceptivesLowDelayed gastric emptying may affect absorption timing
• WarfarinModerate
• CyclosporineModerate

Population Constraints

• PregnancyReproductive SafetyAbsolute
• Pediatric patients (<18 years)AgeRelative
• Lactation / BreastfeedingReproductiveRelative
• Severe renal impairment / End-stage renal diseaseRenalRelative
• History of pancreatitisGastrointestinalRelative
• Severe gastrointestinal diseaseGastrointestinalRelative

Regulatory Status

• European UnionApprovedApproved: Type 2 diabetes mellitus — approved by EMA (Mounjaro) in September 2023, Chronic weight management — approved by EMA (Mounjaro) in 2024EMA granted approval for both indications; thyroid tumor warning included in SmPC.
• United StatesApprovedApproved: Type 2 diabetes mellitus (as adjunct to diet and exercise) — approved May 2022 as Mounjaro, Chronic weight management in adults with BMI ≥30 or ≥27 with weight-related comorbidity — approved November 2023 as ZepboundBlack box warning for thyroid C-cell tumors. REMS not required but Risk Evaluation program in place.
• United KingdomApprovedApproved: Type 2 diabetes mellitus — approved by MHRA (Mounjaro), Chronic weight management — approved by MHRA (Mounjaro) 2024MHRA approved post-Brexit independently; NICE technology appraisal completed for weight management indication.

FDA approved Mounjaro (tirzepatide) for type 2 diabetes in May 2022. FDA approved Zepbound (tirzepatide) for chronic weight management in adults with obesity or overweight with a weight-related comorbidity in November 2023. Approved in the EU and UK under respective brand names for both indications.

Evidence & Sources

No sources recorded yet.