NCT04844918: SURMOUNT-J

A Study of Tirzepatide (LY3298176) in Participants With Obesity Disease

Completed Phase 3 Results posted Last updated 16 July 2024

What this trial tests

Phase 3 trial testing Tirzepatide in Obesity in 267 participants. Completed in 24 June 2023.

Timeline

10 May 2021

Primary endpoint
24 June 2023

24 June 2023

Quick facts

Lead sponsor	Eli Lilly and Company
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	267
Start date	10 May 2021
Primary completion	24 June 2023
Estimated completion	24 June 2023
Sites	18 locations across Japan

Drugs / interventions tested

• Tirzepatide (TIRZEPATIDE) — full drug profile →
• Placebo

Conditions studied

• Obesity — all drugs for Obesity →

Sponsor

Eli Lilly and Company — full company profile →

Who can join

20 and older, any sex, with Obesity. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Mean Percent Change in Body Weight Primary · Baseline, 72 Weeks

Mean percent change in body weight was measured. Least squares (LS) mean was determined using mixed model repeated measures (MMRM) model with Baseline + impaired glucose tolerance (IGT) at Screening + Hyperlipidemia at Screening + non-alcoholic fatty liver disease (NAFLD) at Screening + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Group	Value	95% CI
10 mg Tirzepatide	-17.8	± 0.94
15 mg Tirzepatide	-22.7	± 0.90
Placebo	-1.7	± 0.90

Percentage of Participants Who Achieve ≥5% Body Weight Reduction Primary · Week 72

Percentage of Participants Who Achieve ≥5% Body Weight Reduction

Group	Value	95% CI
10 mg Tirzepatide	94.37
15 mg Tirzepatide	96.05
Placebo	20

Percentage of Participants Who Had Improvement in Obesity-related Health Problems Secondary · Week 72

Percentage of participants who had improvement in obesity-related health problems

Group	Value	95% CI
10 mg Tirzepatide	70.0
15 mg Tirzepatide	79.69
Placebo	11.11

Change From Baseline in Fasting Glucose for Participants With IGT at Baseline Secondary · Baseline, Week 72

Change from Baseline in Fasting Glucose for Participants with IGT at Baseline. LS mean was determined by MMRM model with = Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Group	Value	95% CI
10 mg Tirzepatide	-12.81	± 1.490
15 mg Tirzepatide	-10.61	± 1.391
Placebo	2.19	± 1.291

Change From Baseline in Oral Glucose Tolerance (OGTT) 2-hr Glucose for Participants With Impaired Glucose Tolerance (IGT) at Baseline Secondary · Baseline, Week 72

Change from Baseline in OGTT 2-hr Glucose for Participants with IGT at Baseline. LS mean was determined by MMRM model with Baseline + Hyperlipidemia at Screening + NAFLD at Screening + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Group	Value	95% CI
10 mg Tirzepatide	-61.50	± 5.330
15 mg Tirzepatide	-70.56	± 4.951
Placebo	-5.74	± 4.612

Percent Change From Baseline in Fasting Lipids [Triglycerides (TG)] for Participants With Hyperlipidemia at Baseline Secondary · Baseline, Week 72

Percent Change from Baseline in Fasting Lipids TG for Participants with Hyperlipidemia at Baseline. LS mean was determined by MMRM model with log (Baseline) + NAFLD at Screening + IGT at Screening + Sex + Treatment + Time + Treatment\*Time (Type III sum of squares) as variables.

Group	Value	95% CI
10 mg Tirzepatide	-47.3	± 3.34
15 mg Tirzepatide	-50.6	± 2.77
Placebo	-11.0	± 5.14

Percent Change From Baseline in Hepatic Fat Fraction (HFF) for Participants With Non-alcoholic Fatty Liver Disease [NAFLD] Secondary · Baseline, Week 72

Percent Change from Baseline in HFF for participants diagnosed as NAFLD by MRI at Baseline. LS mean was determined by ANCOVA model with Baseline + Hyperlipidemia at Screening + IGT at Screening + Sex + Treatment (Type III sum of squares) as variables. Percent Change from Baseline in HFF for participants with NAFLD is reported. NAFLD was diagnosed by Magnetic Resonance Imaging (MRI) at Baseline. This was evaluated only for participants who were diagnosed with NAFLD at baseline by MRI.

Group	Value	95% CI
10 mg Tirzepatide	-63.9	± 3.09
15 mg Tirzepatide	-69.9	± 2.99
Placebo	-19.6	± 3.05

Percentage of Participants Who Achieved Improvements of IGT Secondary · Week 72

Percentage of Participants Who Achieved Improvements of IGT. This was evaluated only for participants with IGT at baseline.

Group	Value	95% CI
10 mg Tirzepatide	92.50
15 mg Tirzepatide	97.83
Placebo	28.0

Percentage of Participants Who Achieved Improvements of Hyperlipidemia Secondary · Week 72

Percentage of Participants Who Achieved Improvements of Hyperlipidemia. This was evaluated only for participants with hyperlipidemia at baseline.

Group	Value	95% CI
10 mg Tirzepatide	72.41
15 mg Tirzepatide	81.08
Placebo	25

Percentage of Participants Who Achieved Improvements of NAFLD Secondary · Week 72

Percentage of Participants Who Achieved Improvements of NAFLD. This was evaluated only for participants who were diagnosed as NAFLD by MRI at Baseline.

Group	Value	95% CI
10 mg Tirzepatide	69.49
15 mg Tirzepatide	77.42
Placebo	9.84

Percentage of Participants Who Achieve ≥10% Body Weight Reduction Secondary · Week 72

Percentage of Participants Who Achieve ≥10% body weight reduction.

Group	Value	95% CI
10 mg Tirzepatide	85.92
15 mg Tirzepatide	92.11
Placebo	4

Percentage of Participants Who Achieve ≥15% Body Weight Reduction Secondary · Week 72

Percentage of Participants Who Achieve ≥15% body weight reduction.

Group	Value	95% CI
10 mg Tirzepatide	63.38
15 mg Tirzepatide	82.89
Placebo	1.33

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline Through Safety Follow-Up (Up To 76 Weeks). Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

10 mg Tirzepatide

Serious: 8/73 (11%)

Deaths: 0/73

15 mg Tirzepatide

Serious: 5/77 (6%)

Deaths: 0/77

Placebo

Serious: 5/75 (7%)

Deaths: 0/75

Serious adverse events (18 terms)

Reaction	System	10 mg Tirzepatide	15 mg Tirzepatide	Placebo
Acute myocardial infarction	Cardiac disorders	—	—	—
Vertigo positional	Ear and labyrinth disorders	—	—	—
Rhegmatogenous retinal detachment	Eye disorders	—	—	—
Large intestine polyp	Gastrointestinal disorders	—	—	—
Appendicitis	Infections and infestations	—	—	—
Covid-19	Infections and infestations	—	—	—
Gastroenteritis	Infections and infestations	—	—	—
Otitis media chronic	Infections and infestations	—	—	—
Pneumonia bacterial	Infections and infestations	—	—	—
Pyelonephritis acute	Infections and infestations	—	—	—
Endometrial adenocarcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Oesophageal carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Prostate cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Uterine cancer	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—
Brain stem infarction	Nervous system disorders	—	—	—
Cerebral infarction	Nervous system disorders	—	—	—
Acute kidney injury	Renal and urinary disorders	—	—	—
Benign prostatic hyperplasia	Reproductive system and breast disorders	—	—	—

Other adverse events (201 terms — click to expand)

Reaction	System	10 mg Tirzepatide	15 mg Tirzepatide	Placebo
Constipation	Gastrointestinal disorders	—	—	—
Nausea	Gastrointestinal disorders	—	—	—
Covid-19	Infections and infestations	—	—	—
Pyrexia	General disorders	—	—	—
Diarrhoea	Gastrointestinal disorders	—	—	—
Vomiting	Gastrointestinal disorders	—	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—	—
Nasopharyngitis	Infections and infestations	—	—	—
Abdominal discomfort	Gastrointestinal disorders	—	—	—
Headache	Nervous system disorders	—	—	—
Injection site reaction	General disorders	—	—	—
Immunisation reaction	Injury, poisoning and procedural complications	—	—	—
Arthralgia	Musculoskeletal and connective tissue disorders	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—
Abdominal pain upper	Gastrointestinal disorders	—	—	—
Dental caries	Gastrointestinal disorders	—	—	—
Dyspepsia	Gastrointestinal disorders	—	—	—
Malaise	General disorders	—	—	—
Cystitis	Infections and infestations	—	—	—
Herpes zoster	Infections and infestations	—	—	—
Contusion	Injury, poisoning and procedural complications	—	—	—
Albumin urine present	Investigations	—	—	—
Amylase increased	Investigations	—	—	—
Type 2 diabetes mellitus	Metabolism and nutrition disorders	—	—	—
Dizziness	Nervous system disorders	—	—	—
Urticaria	Skin and subcutaneous tissue disorders	—	—	—
Anaemia	Blood and lymphatic system disorders	—	—	—
Vertigo positional	Ear and labyrinth disorders	—	—	—
Abdominal distension	Gastrointestinal disorders	—	—	—
Abdominal pain	Gastrointestinal disorders	—	—	—
Diverticulum intestinal	Gastrointestinal disorders	—	—	—
Eructation	Gastrointestinal disorders	—	—	—
Flatulence	Gastrointestinal disorders	—	—	—
Large intestine polyp	Gastrointestinal disorders	—	—	—
Stomatitis	Gastrointestinal disorders	—	—	—
Seasonal allergy	Immune system disorders	—	—	—
Gastroenteritis	Infections and infestations	—	—	—
Tinea pedis	Infections and infestations	—	—	—
Tooth abscess	Infections and infestations	—	—	—
Blood creatine phosphokinase increased	Investigations	—	—	—

Most-reported serious reactions: Acute myocardial infarction, Vertigo positional, Rhegmatogenous retinal detachment, Large intestine polyp, Appendicitis, Covid-19, Gastroenteritis, Otitis media chronic.

Data from ClinicalTrials.gov NCT04844918 adverse events section.

Sponsor's own description

The main purpose of this study is to learn more about tirzepatide in participants with obesity disease. The study will also measure how Tirzepatide affects body weight with a low-calorie diet and increased physical activity. The study will last around 72 Weeks.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Pharmacotherapy of obesity: an update on the available medications and drugs under investigation.
   Chakhtoura M, Haber R, Ghezzawi M, Rhayem C, et al · · 2023 · cited 260× · PMID 36992862 · DOI 10.1016/j.eclinm.2023.101882
2. Signaling pathways in obesity: mechanisms and therapeutic interventions.
   Wen X, Zhang B, Wu B, Xiao H, et al · · 2022 · cited 245× · PMID 36031641 · DOI 10.1038/s41392-022-01149-x
3. Transforming obesity: The advancement of multi-receptor drugs.
   Kusminski CM, Perez-Tilve D, Müller TD, DiMarchi RD, et al · · 2024 · cited 77× · PMID 39059360 · DOI 10.1016/j.cell.2024.06.003
4. Tirzepatide and prevention of chronic kidney disease.
   Bosch C, Carriazo S, Soler MJ, Ortiz A, et al · · 2023 · cited 46× · PMID 37151412 · DOI 10.1093/ckj/sfac274
5. New pharmacological agents and novel cardiovascular pharmacotherapy strategies in 2022.
   Tamargo J, Agewall S, Borghi C, Ceconi C, et al · · 2023 · cited 25× · PMID 37169875 · DOI 10.1093/ehjcvp/pvad034
6. Efficacy and safety of once-weekly tirzepatide in Japanese patients with obesity disease (SURMOUNT-J): a multicentre, randomised, double-blind, placebo-controlled phase 3 trial.
   Kadowaki T, Kiyosue A, Shingaki T, Oura T, et al · · 2025 · cited 13× · PMID 40031941 · DOI 10.1016/s2213-8587(24)00377-2
7. Dose-Dependent Efficacy and Safety of Tirzepatide for Weight Loss in Non-diabetic Adults With Obesity: A Systematic Review and Meta-analysis of Randomized Controlled Trials.
   Kasagga A, Assefa AK, Amin MN, Hashish R, et al · · 2025 · cited 4× · PMID 40630338 · DOI 10.7759/cureus.85531
8. The Genetic Blueprint of Obesity: From Pathogenesis to Novel Therapies.
   Tonin G, Eržen S, Mlinarič Z, Eržen DJ, et al · · 2025 · cited 3× · PMID 40650397 · DOI 10.1111/obr.13978