FDA approves tirzepatide, first dual incretin agonist for type 2 diabetes
The FDA announced it approved the injectable dual incretin agonist tirzepatide to improve glucose response in adults with type 2 diabetes in addition to diet and exercise.
Tirzepatide (Mounjaro, Eli Lilly) is a first-in-class medicine that activates both the GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptors, which leads to improved glucose control. Tirzepatide is injected once weekly, with the dose adjusted as tolerated to meet blood glucose goals.
“Given the challenges many patients experience in achieving their target blood sugar goals, today’s approval of Mounjaro is an important advance in the treatment of type 2 diabetes,” Patrick Archdeacon, MD, associate director of the division of diabetes, lipid disorders and obesity in the FDA’s Center for Drug Evaluation and Research, said in a press release.
As Healio previously reported, the SURPASS clinical trial program, which assessed three different doses of tirzepatide (5 mg, 10 mg and 15 mg) across five trials, demonstrated that tirzepatide significantly reduced HbA1c for adults with type 2 diabetes with low rates of hypoglycemia. Tirzepatide was compared against placebo, the GLP-1 receptor agonist semaglutide (Ozempic, Novo Nordisk) and two long-acting insulin analogs.
On average, patients randomly assigned the 15 mg dose of tirzepatide experienced a 1.6% decrease in HbA1c vs. placebo and 1.5% more than placebo when used in combination with a long-acting insulin.
In trials comparing tirzepatide with other diabetes medications, patients who received the 15 mg dose experienced a 0.5% greater reduction in HbA1c compared with patients assigned semaglutide, a 0.9% greater reduction compared with those assigned insulin degludec (Tresiba, Novo Nordisk) and a 1% greater reduction compared with those assigned insulin glargine (Lantus, Sanofi).
Obesity was common among study participants, with an average BMI of 32 to 34 kg/m2 at enrollment. Among patients randomized to 15 mg dose, average weight loss with tirzepatide was 15 pounds more than placebo when neither were used with insulin and 23 pounds more than placebo when both were used with insulin.
Adverse events with tirzepatide include nausea, vomiting, diarrhea, decreased appetite, constipation, upper abdominal discomfort and abdominal pain.
The FDA noted that tirzepatide causes thyroid C-cell tumors in rats; it is unknown whether the drug causes such tumors, including medullary thyroid cancer, in humans. Tirzepatide should not be used in patients with a personal or family history of medullary thyroid cancer or in patients with multiple endocrine neoplasia syndrome type 2, according to the FDA.
Tirzepatide has not been studied in patients with a history of pancreatitis and it is not indicated for use in people with type 1 diabetes, the agency stated in the release.
Tirzepatide received priority review designation for this indication from the FDA. A priority review designation directs overall attention and resources to the evaluation of applications for drugs that, if approved, would be significant improvements in the safety or effectiveness of the treatment, diagnosis or prevention of serious conditions.