Once-weekly Mounjaro now available in Canada for treatment of type 2 diabetes

Eli Lilly is introducing Mounjaro (tirzepatide subcutaneous [SC] injection) for once-weekly administration as an adjunct to diet and exercise to improve glycemic control in the treatment of adults with type 2 diabetes.1,2 Mounjaro can be used as monotherapy when metformin is inappropriate due to a contraindication or intolerance. It can also be used in combination with metformin; metformin and a sulfonylurea; metformin and a sodium-glucose cotransporter 2 inhibitor; or with basal insulin with or without metformin. Tirzepatide has not been studied in combination with short-acting, medium-acting or dual-formulation insulins.1 Tirzepatide should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. It is also not approved for use as a weight loss agent.1 Tirzepatide is being described as the first “twincretin” for type 2 diabetes because of its dual mechanism of action; it is a glucose-dependent insulinotropic polypeptide (GIP) agonist and a glucagon-like peptide-1 (GLP-1) receptor agonist. Tirzepatide enhances first- and second-phase insulin secretion and reduces plasma glucagon levels, both in a glucose-dependent manner. The drug’s half-life is approximately five days.1 Mounjaro is supplied as a solution for SC injection in 2.5 mg/0.5 mL, 5 mg/0.5 mL, 7.5 mg/0.5 mL, 10 mg/0.5 mL, 12.5 mg/0.5 mL and 15 mg/0.5 mL single-use, single-dose vials.2 The recommended starting dose is 2.5 mg SC once weekly; this dose is for treatment initiation and is not intended to be a therapeutic dose. After four weeks, the dose is increased to 5 mg once weekly. If additional glycemic control is needed, the dose can be increased in 2.5 mg increments after at least four weeks at each dose level. The maximum recommended dose is 15 mg once weekly.1 No dose adjustment is required in patients with renal impairment, hepatic insufficiency or in patients > 65 years of age. Regular self-monitoring of blood glucose is not needed to adjust the dose. However, when starting treatment in combination with a sulfonylurea or insulin, self-monitoring of blood glucose may be needed to reduce the dose of the sulfonylurea or insulin in order to reduce the risk of hypoglycemia.1 Tirzepatide can be administered at any time of day, with or without meals. The drug should be injected SC in the abdomen, thigh or upper arm. Injection sites should be rotated with each dose. Patients should be trained on proper injection technique.1 Health Canada approval of Mounjaro was based on results from the phase 3 SURPASS program, which included active comparators of injectable semaglutide 1 mg, insulin glargine and insulin degludec. Efficacy was evaluated for tirzepatide 5 mg, 10 mg and 15 mg, used alone or in combination with commonly prescribed diabetes medications, including metformin, SGLT2 inhibitors, sulfonylureas and insulin glargine. Participants in the SURPASS program achieved average A1C reductions of 1.8%–2.1% for the 5 mg dose and 1.7%–2.4% for the 10 mg and 15 mg doses. Although Mounjaro is not indicated for weight management, the mean change in body weight was a key secondary endpoint in all SURPASS studies. Participants treated with tirzepatide lost an average of 5.4 kg with the 5 mg dose and 11.3 kg with the 15 mg dose.2 The most common adverse effects of tirzepatide are gastrointestinal, including nausea, diarrhea, vomiting, dyspepsia, constipation, abdominal pain and decreased appetite. Most of these reactions are mild or moderate in severity. The majority of reports of nausea, vomiting and/or diarrhea occur during dose escalation and decrease over time.1 More serious adverse effects include the potential risk of thyroid C-cell tumors; the drug is contraindicated in patients with a personal or family history of medullary thyroid carcinoma and in patients with multiple endocrine neoplasia syndrome type 2. Acute pancreatitis, increase in heart rate and hypersensitivity reactions (e.g., urticaria and eczema, sometimes severe) have been reported. Some gastrointestinal adverse effects can be severe leading to dehydration, a deterioration in renal function and acute renal failure.1 In terms of drug interactions, tirzepatide delays gastric emptying, which could affect the absorption of concomitantly administered oral medications. The manufacturer advises that patients using oral hormonal contraceptives should switch to a nonoral contraceptive method or add a barrier method of contraception for four weeks after starting tirzepatide and for four weeks after each dose escalation.1 Caution is recommended if tirzepatide is administered with other drugs that increase heart rate (e.g., drugs with sympathomimetic or anticholinergic activity).1 Using tirzepatide in combination with an insulin secretagogue (e.g., a sulfonylurea) or insulin can increase the risk of hypoglycemia; this risk may be lessened by reducing the dose of the insulin secretagogue or insulin. Tirzepatide is not recommended in combination with other incretin drugs (e.g., GLP-1 receptor agonists or DPP-4 inhibitors), as such combinations have not been studied.1 Mounjaro should be stored in the refrigerator at 2°C–8°C, in the original carton to protect from light. However, it can be stored unrefrigerated for up to 21 days at temperatures not exceeding 30°C.1 Medical Letter consultants have concluded that once-weekly tirzepatide can reduce A1C and weight in adults with type 2 diabetes. In clinical trials in patients with type 2 diabetes, it reduced A1C and body weight more than semaglutide (Ozempic), insulin degludec (Tresiba) or insulin glargine (Lantus). In another trial, tirzepatide reduced body weight substantially in overweight or obese patients without type 2 diabetes, but to date the drug is not approved for weight management. Gastrointestinal adverse effects are common, as with selective GLP-1 receptor agonists. The effects of tirzepatide on the risk of major adverse cardiovascular events remains to be determined.3 References 1. Eli Lilly Canada Inc. Mounjaro (tirzepatide), the first and only single molecule GIP and GLP-1 receptor agonist for the treatment of adults with type 2 diabetes is now available in Canada. (accessed November 6, 2023). 2. Eli Lilly Canada Inc. Mounjaro ((tirzepatide injection) product monograph. Toronto, ON; August 30, 2023. (accessed November 6, 2023). 3. Anon. Tirzepatide (Mounjaro) for type 2 diabetes. Med Lett Drugs Ther 2022;63:105-7.

Once-weekly Mounjaro now available in Canada for treatment of type 2 diabetes

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