Tirzepatide

(Zepbound®)

Zepbound®

Drug updated on 12/11/2024

Dosage FormInjection (subcutaneous; 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg, or 15 mg per 0.5 mL)
Drug ClassGlucagon-like peptide 1 (GLP-1) receptor agonists
Ongoing and
Completed Studies
ClinicalTrials.gov

Indication

  • Indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 30 kg/m2 or greater (obesity)
  • Indicated as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management in adults with an initial body mass index (BMI) of 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, dyslipidemia, type 2 diabetes mellitus, obstructive sleep apnea or cardiovascular disease).

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Summary
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  • This summary is based on the review of 13 systematic review(s)/meta-analysis(es). [1-13]
  • Weight Loss: Tirzepatide significantly reduced body weight, body mass index (BMI), and waist circumference compared to placebo, GLP-1 receptor agonists (GLP-1 RAs), and insulin. Weight loss was dose-dependent, with mean differences in body weight percentage change ranging from -8.07% to -11.83%, and absolute weight loss ranging from -7.5 kg to -11.5 kg, depending on the dose.
  • Glycaemic Control: Tirzepatide led to significant reductions in hemoglobin A1c (HbA1c) and fasting serum glucose (FSG) levels compared to placebo and other antihyperglycaemic drugs, demonstrating its efficacy in improving glycaemic outcomes.
  • Metabolic Markers: Tirzepatide improved various metabolic markers, including reductions in blood pressure, triglycerides, and increases in high-density lipoprotein (HDL) cholesterol. It also showed improvements in fasting blood glucose and lipid profiles, particularly in higher dose groups.
  • Cardiovascular Outcomes: Tirzepatide showed no significant increase in the risk of major cardiovascular events (MACE-4) compared to controls, with potential advantages in reducing cardiovascular outcomes among GLP-1 RAs.
  • Tirzepatide was associated with higher risks of nausea (odds ratio (OR) 4.26), vomiting (OR 8.35), and diarrhea (OR 3.57) compared to placebo.
  • Gastrointestinal side effects were the most frequently reported, generally mild-to-moderate and transient.
  • No significant increase in the risk of pancreatitis but a noted increase in composite gallbladder or biliary diseases.
  • The reviewed documents included overweight/obese adults with and without type 2 diabetes, with subgroup analyses showing stronger effects of tirzepatide at higher doses for weight loss and metabolic outcomes, as well as an increased risk of hypoglycemia and composite gallbladder or biliary diseases at higher doses.

Product Monograph / Prescribing Information

Document TitleYearSource
Zepbound (tirzepatide) Prescribing Information.2024Lilly USA, LLC., Indianapolis, IN

Systematic Reviews / Meta-Analyses

Document TitleYearSource
Efficacy and safety of tirzepatide versus placebo in overweight or obese adults without diabetes: a systematic review and meta-analysis of randomized controlled trials2024International Journal of Clinical Pharmacy
Efficacy and safety of once-weekly tirzepatide for weight management compared to placebo: An updated systematic review and meta-analysis including the latest SURMOUNT-2 trial2024Endocrine
Evaluating the Efficacy and Safety of Tirzepatide on Glycaemic and Non-glycaemic Outcomes in Diabetes: A Systematic Review of Meta-Analyses2024Cureus
Pulse of Progress: A Systematic Review of Glucagon-Like Peptide-1 Receptor Agonists in Cardiovascular Health2024Cardiology Research
Potent incretin-based therapy for obesity: A systematic review and meta-analysis of the efficacy of semaglutide and tirzepatide on body weight and waist circumference, and safety2024Obesity Reviews
The Effect of Tirzepatide on Weight, Lipid Metabolism and Blood Pressure in Overweight/Obese Patients with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis2024Diabetes, Metabolic Syndrome and Obesity
Tirzepatide as a novel effective and safe strategy for treating obesity: a systematic review and meta-analysis of randomized controlled trials2024Frontiers in Public Health
Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis2023Frontiers in Endocrinology
The effects of subcutaneous Tirzepatide on obesity and overweight: a systematic review and meta-regression analysis of randomized controlled trials2023Frontiers in Endocrinology
Weight loss with subcutaneous semaglutide versus other glucagon-like peptide 1 receptor agonists in type 2 diabetes: a systematic review2023Internal Medicine Journal
Weight loss efficiency and safety of tirzepatide: A Systematic review2023PloS One
A systematic review of the safety of tirzepatide-a new dual GLP1 and GIP agonist - is its safety profile acceptable?2023Frontiers in Endocrinology,
Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis2022 Nature Medicine