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