Japan approves Mounjaro (tirzepatide) for type 2 diabetes, a first for its drug class

Japan's Ministry of Health, Labour and Welfare approved Mounjaro (tirzepatide) for the treatment of type 2 diabetes on September 26, 2022, Eli Lilly Japan K.K. and Mitsubishi Tanabe Pharma Corporation announced ^[1]. The companies said it is the world's first sustained-release GIP and GLP-1 receptor agonist to be approved for that use ^[1].

The approval covers a once-weekly subcutaneous injection sold in single-use autoinjectors branded ATEOS, in strengths of 2.5 mg, 5 mg, 7.5 mg, 10 mg, 12.5 mg and 15 mg ^[1]. Tirzepatide is a single molecule that activates two receptors: GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) ^[1]. The Japanese label lists a starting dose of 2.5 mg once weekly, increasing to 5 mg once weekly after four weeks, with further increases of 2.5 mg at intervals of four weeks or longer if the effect is insufficient, up to a maximum of 15 mg once weekly ^[1]. That schedule is specific to the Japanese approval.

The decision rests mainly on two Japanese phase 3 studies and two global ones ^[1]. SURPASS J-mono enrolled 636 adults with type 2 diabetes whose blood sugar was not controlled by diet and exercise alone or by a single oral diabetes drug; it compared tirzepatide 5 mg, 10 mg and 15 mg with dulaglutide 0.75 mg over 52 weeks, and the release says tirzepatide at all three doses was superior on the primary endpoint, change in HbA1c from baseline ^[1]. SURPASS J-combo enrolled 443 adults taking one oral diabetes medicine other than a DPP-4 inhibitor, and its primary endpoint was how often adverse events occurred over 52 weeks with tirzepatide added ^[1].

The global studies were SURPASS-1, which enrolled 478 adults, 89 of them in Japan, and compared tirzepatide with placebo over 40 weeks, and SURPASS-5, which enrolled 475 adults, 82 of them in Japan, and tested 10 mg and 15 mg added to once-daily insulin glargine with or without metformin over 40 weeks ^[1]. The announcement did not report HbA1c or weight results from any of the four trials, so those figures are not yet known ^[1].

"By providing a new option for Japanese patients facing type 2 diabetes, we will expand the range of treatment and contribute to solving unmet medical needs," said Yoshihiro Kobayashi, head of MTPC's Pharma Business Strategy Division ^[1]. Mary Thomas, a senior director in Eli Lilly Japan's diabetes and growth hormone business unit, said Japan "has pioneered many advances in GIP and GLP1 research" ^[1].

Mounjaro was approved in the United States on May 13, 2022 and launched there on June 7, and was approved in the European Union on September 15, 2022 ^[1]. Eli Lilly Japan and MTPC signed a sales collaboration for Japan in July 2022; MTPC will distribute and sell the drug, and the two companies will provide information jointly ^[1].

Why it matters for patients

Mounjaro had already been approved and launched in the United States for type 2 diabetes months before Japan's decision, so this approval does not change what is available to patients in the US ^[1]. It does add a second regulator's review of the same medicine, and two of the four supporting trials were conducted in Japan, which is one more piece of evidence about how the drug performs in a different population ^[1].

Mounjaro contains tirzepatide, a molecule that acts on GIP and GLP-1 receptors ^[1]. It is not semaglutide, the molecule in Ozempic, Wegovy and Rybelsus. The Japanese approval covers type 2 diabetes only; no weight-management approval for tirzepatide in Japan was announced ^[1]. The release did not disclose a price in Japan or whether Japanese public insurance will cover it ^[1].

It also matters which trials support an approval and which patients were studied. Here, tirzepatide was compared with dulaglutide, with placebo, or added to existing oral medicines and insulin — not with semaglutide or with each other's newer competitors ^[1].

What happens next

No launch date in Japan has been disclosed ^[1]. Tirzepatide is also in phase 3 development for chronic weight management, heart failure with preserved ejection fraction and non-alcoholic steatohepatitis, according to the companies ^[1].