As a pharmacy doctor, you will hear buzz about new injectable Mounjaro (tirzepatide), the first "twincretin" for type 2 diabetes. Think of Mounjaro as similar to a glucagon-like peptide-1 (GLP-1) agonist, BUT it’s also a glucose-dependent insulinotropic polypeptide (GIP) agonist. More twincretins are in the works.
GLP-1 and GIP stimulate insulin release, increase satiety, and decrease glucose production. Both hormones are secreted in the gut in response to food, so the dual mechanism doesn’t seem to increase risk of hypoglycemia. Point out that adding once-weekly Mounjaro to metformin (Glucophage) reduces A1c by up to 2.3%, similar to Ozempic (semaglutide), the most "potent" GLP-1 agonist, when either is titrated to max doses.
The max Mounjaro dose is 15 mg/week. But it takes months to reach this dose and there’s not much more A1c lowering over 5 mg/week. Mounjaro may also lead to weight loss of up to 25 lb (11 kg) over 10 months in patients with diabetes, about 10 lb (4.5 kg) more than Ozempic.
Consider downsides. Data on Mounjaro’s cardiovascular (CV) outcomes aren’t expected until 2025. But some GLP-1 agonists (Ozempic, etc) or SGLT2 inhibitors (Jardiance, etc) are shown to lower CV risk.
Plus Mounjaro has GI side effects similar to GLP-1 agonists, also carries warnings of rare pancreatitis, gallbladder disease, and thyroid tumors. When a metformin add-on is needed for patients at high CV risk, lean toward a GLP-1 agonist or SGLT2 inhibitor with proven CV benefit. But think of Mounjaro for patients at lower CV risk, especially if maximizing weight loss is a priority and payer coverage isn’t a barrier.
Be aware that Mounjaro labeling cautions about possible reduced efficacy of oral contraceptives due to delayed gastric emptying. This effect lessens with time. Suggest a non-oral method (ring, IUD, etc) or backup for 4 weeks after starting and each titration.
You will also hear Mounjaro may lead to weight loss of up to 47 lb (21 kg) over 18 months in patients with obesity but withOUT diabetes. But don’t recommend it for weight loss alone yet, it’s not approved and likely won’t be covered.
REFERENCES
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FrÃas JP, Davies MJ, Rosenstock J, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. Available at: https://www.nejm.org/doi/10.1056/NEJMoa2107519
FrÃas JP, Auerbach P, Bajaj HS, Fukushima Y, Lingvay I, Macura S, Søndergaard AL, Tankova TI, Tentolouris N, Buse JB. Efficacy and safety of once-weekly semaglutide 2·0 mg versus 1·0 mg in patients with type 2 diabetes (SUSTAIN FORTE): a double-blind, randomised, phase 3B trial. Lancet Diabetes Endocrinol. 2021 Sep;9(9):563-574. Available at: https://pubmed.ncbi.nlm.nih.gov/34293304/
Jastreboff, A.M., Aronne, L.J., Ahmad, N.N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M.C. and Stefanski, A. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine. Available at: https://www.nejm.org/doi/full/10.1056/NEJMoa2206038