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Tirzepatide

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Tirzepatide, Mounjaro, Twincretin, GIP Agonist, Zepbound

  • See Also
  1. GLP-1 Agonist
  2. Type II Diabetes Medications
  3. Obesity Medication
  4. Dulaglutide
  5. Exenatide
  6. Liraglutide
  7. Lixisenatide
  8. Semaglutide
  • Indications
  1. Type 2 Diabetes Mellitus
  2. Obesity Management
    1. Indicated for BMI>30 kg/m2 (or BMI >27 kg/m2 with at least one weight-related comorbidity)
    2. Adjunct to conservative weight loss measures (e.g. caloric restriction, Physical Activity)
    3. Decreases appetite and food intake
  • Contraindications
  1. Personal or Family History of Medullary Thyroid Cancer
  2. Multiple Endocrine Neoplasia Syndrome
  • Mechanism
  1. Single Agent GLP-1 Agonist and GIP Agonist (Twincretin)
  2. Glucose-Dependent Insulinoptropic Polypeptide (GIP)
    1. Like GLP-1, GIP is another Incretin secreted in the intestinal tract in response to food
    2. Also like GLP-1, GIP stimulates Insulin release, decreases Glucose synthesis and increases satiety
  3. Some GLP-1 Agonists are also active as GIP Agonists ("Twincretins")
    1. See GLP-1 Agonist for mechanism
    2. Tirzeptatide (Mounjaro) is the first drug released in 2022, that is active at both GIP and GLP-1 receptors
  • Medications
  1. Tirzepatide Autoinjectors with 0.5 ml containing 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg or 15 mg
  • Dosing
  1. Dosing is the same for Obesity in non-diabetics (Zepbound) as it is for Diabetes Mellitus (Mounjaro)
  2. No renal or hepatic function adjustments needed
  3. Start: 2.5 mg SQ once weekly for 4 weeks
    1. Cost in 2022: $1000 per month (for 4 of the 2.5 mg pens)
  4. Next: 5 mg SQ once weekly
  5. Titrate: Increase by 2.5 mg/week every 4 weeks
  6. Maintenance: 5 mg/week, 10 mg/week or 15 mg/week
  7. Maximum: 15 mg/week
  • Adverse Effects
  1. See GLP-1 Agonists
  2. Hypoglycemia
    1. Occurs in 4% of patients with diabetes (but <0.5% in non-diabetic patients)
    2. Does not increase Hypoglycemia risk when used as single diabetic agent
  3. Gastrointestinal adverse effects (Nausea, Vomiting, Diarrhea) in 3 to 5% of patients
    1. Eat smaller meals and more slowly, stopping before fullness (satiety)
    2. Infrequently complicated by Acute Kidney Injury
    3. No significant increased risk of Gall Bladder disease or Pancreatitis
  4. Also delays gastric emptying
    1. May render Oral Contraceptives less effective
  5. May increase Suicidality risk (class effect)
  6. No available data in 2022 on cardiovascular benefit (unlike some other GLP-1 Agonists)
  • Safety
  1. Unknown safety in Lactation
  2. Unknown safety in pregnancy
    1. Avoid in pregnancy
  • Efficacy
  1. In combination with Metformin, reduces Hemoglobin A1C up to 2.3%
  2. Weight loss in Diabetes Mellitus patients may approach 25 pound loss in 10 months
  3. Weight loss in patients without Diabetes was 15-21% of total body weight over a 72 week period
    1. Number Needed to Treat (NNT): 2 for one patient to lose >20% of their body weight
    2. Dose 5 mg/week reduced weight 15%
    3. Dose 10 mg/week reduced weight 19.5%
    4. Dose 15 mg/week reduced weight 20.9% (average 41 lbs in 1 year)
    5. References
      1. Jastreboff (2022) N Engl J Med 387(3): 205-16 [PubMed]
  • Drug Interactions
  1. Oral Contraceptives
    1. Delayed Gastric Emptying may reduce OCP efficacy
    2. Use barrier Contraception with OCPs (esp. 4 weeks after starting or after dose excalation)
    3. Consider alternative non-Oral Contraceptives (e.g. IUD, Vaginal Contraceptive Ring)
  • Resources
  1. Mounjaro (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=d2d7da5d-ad07-4228-955f-cf7e355c8cc0
  2. Zepbound (DailyMed)
    1. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=487cd7e7-434c-4925-99fa-aa80b1cc776b
  • References
  1. (2024) Presc Lett 31(2): 8-9
  2. (2022) Presc Lett 29(7): 38-9
  3. Rebitch (2023) Am Fam Physician 108(1): 93-4 [PubMed]
  4. Coppenrath (2024) Am Fam Physician 110(2): 199-200 [PubMed]