The lancet. Diabetes & endocrinologyAug 1, 2022

Effectiveness and safety of tirzepatide alone versus dulaglutide in Japanese adults with type 2 diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 17, 2026

Abstract

At week 52, tirzepatide led to a greater reduction in HbA1c levels compared to dulaglutide, with mean changes of -2.4, -2.6, and -2.8 for the 5 mg, 10 mg, and 15 mg doses, respectively.

Tirzepatide was associated with a mean treatment difference of -1.1, -1.3, and -1.5 compared to dulaglutide for the 5 mg, 10 mg, and 15 mg doses, respectively.
Participants receiving tirzepatide experienced dose-dependent reductions in body weight, with mean differences of -5.8 kg, -8.5 kg, and -10.7 kg for the 5 mg, 10 mg, and 15 mg doses, respectively.
In contrast, dulaglutide was associated with a minimal reduction in body weight of -0.5 kg.
Common treatment-emergent adverse events included nausea, constipation, and nasopharyngitis, with nausea reported in 12% to 20% of tirzepatide participants and 8% in the dulaglutide group.
The safety profile of tirzepatide was consistent with that of existing GLP-1 receptor agonists.

Simplified

BACKGROUND: As the disease progresses, many patients with type 2 diabetes have difficulty in reaching treatment goals. We aimed to assess the efficacy and safety of tirzepatide, a novel GIP and GLP-1 receptor agonist, compared with dulaglutide in Japanese patients with type 2 diabetes.

METHODS: This multicentre, randomised, double-blind, parallel, active-controlled, phase 3 trial was conducted in 46 medical research centres and hospitals in Japan. Adults aged 20 years or older with type 2 diabetes who had discontinued oral antihyperglycaemic monotherapy or were treatment-naïve were included. Participants were randomly assigned (1:1:1:1) to receive tirzepatide (5, 10, or 15 mg) or dulaglutide (0·75 mg) once per week using a computer-generated random sequence with an Interactive Web Response System. Participants were stratified based on baseline HbA(≤8·5% or >8·5%), baseline BMI (<25 or ≥25 kg/m), and washout of antidiabetic medication. Participants, investigators, and the sponsor were masked to treatment assignment. The starting dose of tirzepatide was 2·5 mg once per week for 4 weeks, which was then increased to 5 mg in the tirzepatide 5 mg treatment group. For the tirzepatide 10 and 15 mg treatment groups, increases by 2·5 mg occurred once every 4 weeks until the assigned dose was reached. The primary endpoint was mean change in HbAfrom baseline at week 52 measured in the modified intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03861052. 1c1c2

FINDINGS: Between May 7, 2019, and March 31, 2021, 821 participants were assessed for study eligibility and 636 were randomly assigned to receive at least one dose of tirzepatide 5 mg (n=159), 10 mg (n=158), or 15 mg (n=160), or dulaglutide 0·75 mg (n=159). 615 (97%) participants completed the study and 21 (3%) discontinued. Participants had a mean age of 56·6 years (SD 10·3) and were mostly male (481 [76%]). At week 52, HbAdecreased from baseline by a least squares mean of -2·4 (SE 0·1) for tirzepatide 5 mg, -2·6 (0·1) for tirzepatide 10 mg, -2·8 (0·1) for tirzepatide 15 mg, and -1·3 (0·1) for dulaglutide. Estimated mean treatment differences versus dulaglutide were -1·1 (95% CI -1·3 to -0·9) for tirzepatide 5 mg, -1·3 (-1·5 to -1·1) for tirzepatide 10 mg, and -1·5 (-1·71 to -1·4) for tirzepatide 15 mg (all p<0·0001). Tirzepatide was associated with dose-dependent reductions in bodyweight with a least square mean difference of -5·8 kg (SE 0·4; -7·8% reduction) for 5 mg, -8·5 kg (0·4; -11·0% reduction) for 10 mg, and -10·7 kg (0·4; -13·9% reduction) for 15 mg of tirzepatide compared with -0·5 kg (0·4; -0·7% reduction) for dulaglutide. The most common treatment-emergent adverse events were nausea (19 [12%] participants in the 5 mg group vs 31 [20%] in the 10 mg group vs 32 [20%] in the 15 mg group all receiving tirzepatide vs 12 (8%) in the group receiving dulaglutide), constipation (24 [15%] vs 28 [18%] vs 22 [14%] vs 17 [11%]), and nasopharyngitis (29 [18%] vs 25 [16%] vs 22 [14%] vs 26 [16%]). The most frequent adverse events were gastrointestinal (23 [4%] of 636). 1c

INTERPRETATION: Tirzepatide was superior compared with dulaglutide for glycaemic control and reduction in bodyweight. The safety profile of tirzepatide was consistent with that of GLP-1 receptor agonists, indicating a potential therapeutic use in Japanese patients with type 2 diabetes.

FUNDING: Eli Lilly and Company.

TRANSLATION: For the Japanese translation of the abstract see Supplementary Materials section.

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Declaration of interests NI received research grants and had contracts from Terumo, Drawbridge, Asken, Novartis, Novo Nordisk, Astellas Pharma, Tsumura, Kyowa Kirin, Taisho Pharmaceutical Holdings, Ono Pharmaceutical, Eli Lilly Japan, Sanwa Kagaku Kenkyusho, MSD, Kowa, Kissei Pharmaceutical, Sanofi, Daiichi-Sankyo, Japan Tobacco, Sumitomo Pharma, Mitsubishi Tanabe Pharma, Takeda Pharmaceutical, Nippon Boehringer Ingelheim, Teijin Pharma, Pfizer Japan, FUJIFILM Toyama Chemical, Roche Japan, and LifeScan Japan; honoraria from Kowa, MSD, Astellas Pharma, Kissei Pharmaceutical, Sanofi, Novartis, Novo Nordisk, Ono Pharmaceutical, Kyowa Kirin, Sumitomo Pharma, Daiichi-Sankyo, Eli Lilly Japan, Nippon Boehringer Ingelheim, Takeda Pharmaceutical, Mitsubishi Tanabe Pharma, Taisho Pharmaceutical Holdings, Terumo, AstraZeneca, Sanwa Kagaku Kenkyusho, Abbott Japan, Ajinomoto, Teijin Healthcare, Bayer Yakuhin, Arkray, Johnson and Johnson, and Roche Japan; holds patents with UHA Mikakuto, Asken, and Shiratori Pharmaceutical; and was a member of advisory boards for Bayer Yakuhin, Terumo, Mitsubishi Tanabe Pharma, Sanofi, Novartis, Kowa, Abbott Japan, Novo Nordisk, Scohia Pharma, Sumitomo Pharma, Kissei Pharmaceutical, Nippon Boehringer Ingelheim, and Eli Lilly Japan. YS received grants and contracts from Terumo, Nippon Boehringer Ingelheim, Arkray, Taisho Pharmaceutical Holdings, Novo Nordisk, and Ono Pharmaceutical; and honoraria from MSD, Kao Corporation, Taisho Pharmaceutical Holdings, Takeda Pharmaceutical, Nippon Becton Dickinson, Nippon Boehringer Ingelheim, Novo Nordisk, Sumitomo Pharma, and Ono Pharmaceutical. MT, TO, and TI are employees of Eli Lilly Japan and shareholders in Eli Lilly and Company. TI is a senior director and operating officer for Eli Lilly Japan.

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Effectiveness and safety of tirzepatide alone versus dulaglutide in Japanese adults with type 2 diabetes

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