III. Contraindications

IV. 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. Tirzeptatide (Mounjaro) is the first drug released in 2022, that is active at both GIP and GLP-1 receptors

V. Dosing

  1. Dosing is the same for Obesity in non-diabetics (Zepbound) as it is for Diabetes Mellitus (Mounjaro)
  2. 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)
  3. Next: 5 mg SQ once weekly
  4. Titrate: Increase by 2.5 mg/week every 4 weeks
  5. Maximum: 15 mg/week

VI. Adverse Effects

  1. See GLP-1 Agonists
  2. Gastrointestinal adverse effects (Nausea, Vomiting, Diarrhea) in >5% of patients
    1. Eat smaller meals and more slowly, stopping before fullness (satiety)
  3. Also delays gastric emptying
    1. May render Oral Contraceptives less effective
  4. No available data in 2022 on cardiovascular benefit (unlike some other GLP-1 Agonists)
  5. Does not increase Hypoglycemia risk when used as single diabetic agent

VII. Safety

  1. Unknown safety in Lactation
  2. Unknown safety in pregnancy

VIII. 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. Dose 5 mg/week reduced weight 15%
    2. Dose 10 mg/week reduced weight 19.5%
    3. Dose 15 mg/week reduced weight 20.9% (average 41 lbs in 1 year)
    4. Jastreboff (2022) N Engl J Med 387(3): 205-16 [PubMed]

IX. 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)

XI. 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]

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

mounjaro (on 10/19/2022 at Medicaid.Gov Survey of pharmacy drug pricing)
MOUNJARO 10 MG/0.5 ML PEN $467.27 per ml
MOUNJARO 12.5 MG/0.5 ML PEN $468.25 per ml
MOUNJARO 15 MG/0.5 ML PEN $467.62 per ml
MOUNJARO 2.5 MG/0.5 ML PEN $467.37 per ml
MOUNJARO 5 MG/0.5 ML PEN $467.55 per ml
MOUNJARO 7.5 MG/0.5 ML PEN $467.79 per ml