Tirzepatide

Single Agent GLP-1 Agonist and GIP Agonist (Twincretin)
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
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

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

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

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
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]

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)