Press ReleaseSep 26, 2022
Eli Lilly Japan K.K.
Mitsubishi Tanabe Pharma Corporation

Approval of Mounjaro,
the world’s first sustained release GIP/GLP-1 receptor agonist
for the treatment of type 2 diabetes in Japan
September 26, 2022 - Eli Lilly Japan K.K. (Head Office: Kobe, Japan, Representative Director andPresident: Simone Thomsen, hereinafter called “Eli Lilly Japan”) and Mitsubishi Tanabe Pharma Corporation (Head Office: Osaka, Japan, Representative Director: Hiroaki Ueno, hereinafter called “MTPC”)
announced that Ministry of Health, Labour and Welfare (MHLW) approved the manufacturing and marketing of the following sustained release GIP/GLP-1 receptor agonists: “Mounjaro® subcutaneousinjection 2.5 mg / 5 mg / 7.5 mg / 10 mg / 12.5 mg / 15 mg ATEOS®” (Non-proprietary name: Tirzepatide, hereinafter referred called “Mounjaro”) indicated for “type 2 diabetes” in Japan.
As the world’s first sustained release GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 (glucagon-like peptide-1) receptor agonist, Mounjaro is a single molecule that activates two receptors: GIP
and GLP-1. Although the structure of Mounjaro is a single molecule based on the natural GIP peptide
sequence, it has been modified to also bind to the GLP-1 receptor, and selectively acts for a long time toimprove fasting and postprandial blood glucose. Mounjaro is administered once weekly by subcutaneous
injection with a single-use autoinjector device (ATEOS).
Approval of Mounjaro is based primarily on the efficacy and safety results of two Japanese phase 3
clinical studies (SURPASS J-monoⅰ and SURPASS J-comboⅱ) and two global studies (SURPASS-1ⅲ
and SURPASS-5ⅳ). A Japanese monotherapy study (SURPASS J-monoⅰ) demonstrated the superiorityof Tirzepatide 5 mg, 10 mg, and 15 mg over Dulaglutide 0.75 mg in terms of the mean change from baseline in HbA1c at Week 52, the primary endpoint. In addition, a Japanese combination therapy study (SURPASS J-comboⅱ) evaluated the safety and efficacy of Tirzepatide 5 mg, 10 mg, and 15 mg in combination
with an oral hypoglycemic monotherapy.
Eli Lilly and Company obtained an approval of Mounjaro in the United States on May 13 as the world’s
first sustained release GIP/GLP-1 receptor agonist, and launched it on June 7. Mounjaro was also approved in the European Union on September 15. Prior to this approval, Eli Lilly Japan and MTPC concluded a sales collaboration agreement for Mounjaro in Japan in July. MTPC will distribute and sell Mounjaro, and Eli Lilly Japan and MTPC will jointly provide information.
“We are very pleased to receive approval for Mounjaro to be able to bring a new class of treatment options to people living with type 2 diabetes in Japan. We hope Mounjaro will help them reach their treat-1/3

ment goals. This is an exciting time as Japan has pioneered many advances in GIP and GLP1 research, so we are appreciative of the incredible research accomplishments in Japan and are honored tobring Mounjaro forward to people in Japan with diabetes,” said Mary Thomas, Sr Director, Diabetes andGrowth Hormone Business unit, Ely Lilly Japan.
“We are very pleased that Mounjaro has been approved in Japan. 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 Pharma Business Strategy Division, MTPC.
Product Summary
Product Name

Non-proprietary Name
Indications
Dosage andAdministration

Date of acquisition ofmanufacturing andmarketing approval

Mounjaro® subcutaneous injection 2.5 mg ATEOS®
Mounjaro® subcutaneous injection 5 mg ATEOS®
Mounjaro® subcutaneous injection 7.5 mg ATEOS®
Mounjaro® subcutaneous injection 10 mg ATEOS®
Mounjaro® subcutaneous injection 12.5 mg ATEOS®
Mounjaro® subcutaneous injection 15 mg ATEOS®
Tirzepatide
Type 2 diabetes
For adults, the usual maintenance dose of Tirzepatide is 5 mg once a weekby subcutaneous injection. However, start with 2.5 mg once weekly and increase to 5 mg once weekly after 4 weeks.
The dosage may be adjusted according to the patient's condition, but if theeffect is insufficient with 5 mg once a week, the dosage can be increased by
2.5 mg at intervals of 4 weeks or longer. However, the maximum dosage
should be up to 15 mg once weekly.
September 26, 2022

About SURPASS J-monoⅰ
This is a Japanese phase 3 study evaluating the superiority of 5 mg, 10 mg, and 15 mg of Tirzepatide
once weekly to Dulaglutide 0.75 mg. The study enrolled 636 adults with type 2 diabetes who had inadequate glycemic management with diet and exercise therapy alone, or with oral hypoglycemic agentsalone excluding Thiazolidinediones. The primary endpoint was HbA1c reduction from baseline after 52weeks. The secondary endpoints included body weight and fasting blood glucose.
About SURPASS J-comboⅱ
This is a Japanese phase 3 study evaluating the incidence of adverse events. The study enrolled 443
adults with type 2 diabetes who had inadequate glycemic management despite being on monotherapy
with oral hypoglycemic agents other than DPP-4 inhibitors for at least three months. The primary endpoint was the incidence of adverse events with Tirzepatide 5 mg, 10 mg, and 15 mg once weekly for 52
weeks in concomitant oral hypoglycemic agents (Sulfonylureas, Biguanides, Alpha-glucosidase inhibitors, Thiazolidines, fast-acting Insulin secretagogues or SGLT2 inhibitors). A secondary objective wasto evaluate the efficacy of Tirzepatide once weekly for 52 weeks in combination with oral hypoglycemicagents.
About SURPASS-1ⅲ
This is a global phase 3 study evaluating the superiority of 5 mg, 10 mg, and 15 mg of Tirzepatide once
weekly to placebo. The study enrolled 478 adults (89 Japanese) with type 2 diabetes who had inadequate glycemic management with diet and exercise alone, and naïve to injectable therapy who had not2/3

used any oral antidiabetic medicines within three months.The primary endpoint was HbA1c reduction
from baseline after 40 weeks. The secondary endpoints included body weight and fasting blood glucose.
About SURPASS-5ⅳ
This is a global phase 3 study evaluating the superiority of 10 mg and 15 mg of Tirezpatide once weekly
in combination with placebo. The study enrolled 475 adults (82 Japanese) with type 2 diabetes who
had inadequate glycemic management on once-daily Insulin Glargine with or without metformin. The
primary endpoint was HbA1c reduction from baseline after 40 weeks. The secondary endpoints included body weight and fasting blood glucose.
About Tirzepatide
Tirzepatide is a once-weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon like
peptide-1 (GLP-1) receptor agonist that integrates the actions of both incretins into a single novel molecule. GIP is a hormone that may complement the effects of GLP-1. In preclinical models, GIP has beenshown to decrease food intake and increase energy expenditure therefore resulting in weight reductions, and when combined with a GLP-1 receptor agonist, may result in greater effects on glucose andbody weight. Tirzepatide is in phase 3 development for blood glucose management in adults with type 2
diabetes, for chronic weight management and heart failure with preserved ejection fraction (HFpEF). Itis also being studied as a potential treatment for non-alcoholic steatohepatitis (NASH).
About Eli Lilly Japan
Eli Lilly Japan K.K. is a subsidiary of US-based Eli Lilly and Company. It contributes to medical treatment in Japan through the development, manufacture, import and sale of innovative pharmaceuticalproducts that enable people to live longer, healthier, and more fulfilling lives, focusing on the therapeutic areas such as cancer, diabetes, musculoskeletal diseases, central nervous system diseases, autoimmune diseases, growth disorder, and pain. For more information, visit http://www.lilly.co.jp
About Mitsubishi Tanabe Pharma Corporation
Mitsubishi Tanabe Pharma Corporation (MTPC), the pharma arm of the Mitsubishi Chemical Group, isone of the oldest pharmaceutical companies in the world, founded in 1678, and focusing on ethicalpharmaceuticals. The Mitsubishi Chemical Group has positioned Health Care as one of its strategic focus in its management policy, “Forging the future”. MTPC set the MISSION of “Creating hope for all facing illness”. To that end, MTPC is working on R&D in the areas of central nervous system and immunoinflammation and vaccines for global market, and it is also focusing on the areas of diabetes and kidneydisease in Japan. For more information, go to https://www.mt-pharma.co.jp/e/References
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Inagaki, N, et. al. Efficacy and safety of tirzepatide monotherapy compared with dulaglutide in Japanese patients with type 2 diabetes(SURPASS J-mono): a double-blind, multicentre, randomised, phase 3 trial. Lancet. Diabetes Endocrinol. 2022; (doi: 10.1016/S22138587(22)00188-7)
Kadowaki, T, et.al. Safety and efficacy of tirzepatide as an add-on to single oral antihyperglycaemic medication in patients with type2 diabetes in Japan (SURPASS J-combo): a multicentre, randomised, open-label, parallel-group, phase 3 trial. Lancet Diabetes
Endocrinol. 2022; (doi: 10.1016/S2213-8587(22)00187-5)
Rosenstock, J, et. al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes(SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021; 398(10295): 143-155
Dahl D, Onishi Y, Norwood P, et al. Effect of subcutaneous tirzepatide vs placebo added to titrated insulin glargine on glycemic control
in patients with type 2 diabetes: the SURPASS-5 randomized clinical trial. JAMA. 2022;327(6):534-545. doi:10.1001/jama.2022.0078

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