A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight

Obesity Clinical Trial

— SURMOUNT-2  

Official title:

Efficacy and Safety of Tirzepatide Once Weekly in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight: A Randomized, Double-Blind, Placebo-Controlled Trial (SURMOUNT-2)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04657003
• Other study ID #: 17245
• Secondary ID: I8F-MC-GPHL
• Status: Completed
• Phase: Phase 3
• Start date: March 29, 2021
• Est. completion date: April 10, 2023

Study information

• Verified date: March 2024
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a study of tirzepatide in participants with type 2 diabetes who have obesity or are overweight. The main purpose is to learn more about how tirzepatide affects body weight. The study will last 79 weeks (22 visits).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 938
• Est. completion date: April 10, 2023
• Est. primary completion date: March 16, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Have Type 2 Diabetes (T2DM) with HbA1c =7% to =10% at screening, on stable therapy for the last 3 months prior to screening. T2DM may be treated with diet/exercise alone or any oral glycemic-lowering agent (as per local labeling) EXCEPT dipeptidyl peptidase 4 (DPP-4) inhibitors or glucagon like peptide-1 receptor agonists (GLP-1 RAs)

• Have a BMI of =27 kg/m²

• Are overweight or have obesity

• Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight

• Are at least 18 years of age and age of majority per local laws and regulations

Exclusion Criteria:

• Have Type 1 diabetes mellitus, history of ketoacidosis or hyperosmolar state/coma or any other types of diabetes except T2DM

• Have at least 2 confirmed fasting self-monitoring blood glucose (SMBG) values >270 mg/dL(on 2 nonconsecutive days) prior to Visit 3

• Have proliferative diabetic retinopathy OR diabetic macular edema OR non-proliferative diabetic retinopathy that requires acute treatment

• Have self-reported change in body weight >5kg within 3 months prior to screening

• Have had a history of chronic or acute pancreatitis

• Change in body weight greater than 5 kg within 3 months prior to starting study

• Obesity induced by other endocrinologic disorders or monogenetic or syndromic forms of obesity

• Family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)

• History of significant active or unstable major depressive disorder (MDD) or other severe psychiatric disorder within the last 2 years

• Any lifetime history of a suicide attempt

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Obesity
• Overweight
• Type 2 Diabetes

Intervention

Drug:
• Tirzepatide
Administered SC

Other:
• Placebo
Administered SC

Locations

Country	Name	City	State
Argentina	Centro Médico Viamonte	Buenos Aires	Ciudad Autónoma De Buenos Aire
Argentina	CIPREC	Caba	Ciudad Autónoma De Buenos Aire
Argentina	Consultorio de Investigación Clínica EMO SRL	Ciudad Autonoma de Buenos Aire	Buenos Aires
Argentina	Centro de Investigaciones Metabólicas (CINME)	Ciudad Autónoma de Buenos Aire	Buenos Aires
Argentina	Instituto de Investigaciones Clínicas Mar del Plata	Mar del Plata	Buenos Aires
Argentina	Centro de Investigaciones Médicas Tucuman	SAN M. DE Tucuman	Tucumán
Argentina	Go Centro Medico San Nicolás	San Nicolas	Buenos Aires
Argentina	Sanatorio Norte	Santiago del Estero
Brazil	Instituto de Pesquisa clinica de Campinas	Campinas	São Paulo
Brazil	Loema Instituto de Pesquisa Clinica	Campinas	São Paulo
Brazil	Private Practice - Dr.Miguel N. Hissa	Fortaleza	Ceará
Brazil	CECIP - Centro de Estudos do Interior Paulista	Jaú	São Paulo
Brazil	CPCLIN	Sao Paulo	São Paulo
Brazil	CEPIC - Centro Paulista de Investigação Clínica	São Paulo
India	Life Care Hospital and Research Centre	Bangalore	Karnataka
India	ILS Hospitals	Kolkata	West Bengal
Japan	Medical Corporation Sato Medical clinic	Ootaku	Tokyo
Japan	AMC Nishiumeda Clinic	Osaka
Japan	Medical Corporation Heishinkai OCROM Clinic	Suita-shi	Osaka
Japan	Medical Corporation Yuga Tsuruma Kaneshiro Diabetes Clinic	Yamato-shi	Kanagawa
Puerto Rico	Centro de Endocrinologia y Nutricion	Caguas
Puerto Rico	GCM Medical Group, PSC - Hato Rey Site	San Juan
Puerto Rico	Latin Clinical Trial Center	San Juan
Russian Federation	Endocrinology Research Center of Rosmedtechnologies	Moscow	Moskva
Russian Federation	Russian Medical Academy of Postgraduate Education	Moscow	Moskva
Russian Federation	Saint-Petersburg City Hospital of Saint Elizabeth	Saint Petersburg	Sankt-Pete
Russian Federation	Smolensk State Medical University	Smolensk
Taiwan	Changhua Christian Hospital	Changhua County	Changhua
Taiwan	Chung Shan Medical University Hospital	Taichung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	National Cheng-Kung Uni. Hosp.	Tainan
Taiwan	Chi Mei Medical Center	Tainan City	Tainan
United States	Emory University School of Medicine- Grady Campus	Atlanta	Georgia
United States	Texas Diabetes & Endocrinology, P.A.	Austin	Texas
United States	Maryland Cardiovascular Specialists	Baltimore	Maryland
United States	University of Alabama - Department of Nutrition Sciences	Birmingham	Alabama
United States	Elite Clinical Trials	Blackfoot	Idaho
United States	University of North Carolina Medical Center	Chapel Hill	North Carolina
United States	Velocity Clinical Research, Cleveland	Cleveland	Ohio
United States	ALL Medical Research, LLC	Cooper City	Florida
United States	The Corvallis Clinic, P.C.	Corvallis	Oregon
United States	Dallas Diabetes Research Center	Dallas	Texas
United States	Aventiv Research	Dublin	Ohio
United States	NECCR PrimaCare Research	Fall River	Massachusetts
United States	Northeast Research Institute (NERI)	Fleming Island	Florida
United States	Diabetes and Thyroid Center of Fort Worth	Fort Worth	Texas
United States	American Health Network of Indiana, LLC - Greenfield	Greenfield	Indiana
United States	PharmQuest	Greensboro	North Carolina
United States	Tribe Clinical Research, LLC	Greenville	South Carolina
United States	Pacific Diabetes & Endocrine Center	Honolulu	Hawaii
United States	Endocrine Ips, Pllc	Houston	Texas
United States	Juno Research	Houston	Texas
United States	Velocity Clinical Research, Huntington Park	Huntington Park	California
United States	Rocky Mountain Clinical Research	Idaho Falls	Idaho
United States	Logan Health Research	Kalispell	Montana
United States	Clinical Investigation Specialists	Kenosha	Wisconsin
United States	KLR Business Group, Inc. dba Arkansas Clinical Research	Little Rock	Arkansas
United States	Velocity Clinical Research, Westlake	Los Angeles	California
United States	East Coast Institute for Research, LLC	Macon	Georgia
United States	New Horizon Research Center	Miami	Florida
United States	Catalina Research Institute, LLC	Montclair	California
United States	Health Research of Hampton Roads, Inc.	Newport News	Virginia
United States	West Orange Endocrinology	Ocoee	Florida
United States	MD Medical Research	Oxon Hill	Maryland
United States	Rainier Clinical Research Center	Renton	Washington
United States	Encompass Clinical Research	Spring Valley	California
United States	Cotton O'Neil Clinical Research Center	Topeka	Kansas
United States	Premier Research	Trenton	New Jersey
United States	Arcturus Healthcare , PLC, Troy Internal Medicine Research Division	Troy	Michigan
United States	University Clinical Investigators, Inc.	Tustin	California
United States	Preferred Primary Care Physicians	Uniontown	Pennsylvania
United States	Center for Neurosciences	Warwick	Rhode Island
United States	Iowa Diabetes and Endocrinology Research Center	West Des Moines	Iowa
United States	Metabolic Research Institute, Inc.	West Palm Beach	Florida
United States	Wake Forest University Baptist Medical Center (WFUBMC)	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Argentina,  Brazil,  India,  Japan,  Puerto Rico,  Russian Federation,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent Change From Baseline in Body Weight	Least Squares Mean (LSMean) calculated using Mixed Model Repeated Measures (MMRM) model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of Antihyperglycemic Medication (AHM) Used at Randomization + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Primary	Percentage of Participants Who Achieve =5% Body Weight Reduction From Baseline	Percentage of participants who achieve =5% body weight reduction from baseline	Week 72
Secondary	Percentage of Participants Who Achieve =10% Body Weight Reduction From Baseline	Percentage of participants who achieve =10% body weight reduction from baseline	Week 72
Secondary	Percentage of Participants Who Achieve =15% Body Weight Reduction From Baseline	Percentage of participants who achieve =15% body weight reduction from baseline	Week 72
Secondary	Percentage of Participants Who Achieve =20% Body Weight Reduction From Baseline	Percentage of participants who achieve =20% body weight reduction from baseline	Week 72
Secondary	Change From Baseline in Absolute Body Weight	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Secondary	Change From Baseline in Body Mass Index (BMI)	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Secondary	Change From Baseline in Hemoglobin A1c (HbA1c)	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Secondary	Percentage of Participants Who Achieve HbA1c <7%	Percentage of participants who achieve HbA1c <7%	Week 72
Secondary	Percentage of Participants Who Achieve HbA1c =6.5%	Percentage of participants who achieve HbA1c =6.5%	Week 72
Secondary	Percentage of Participants Who Achieve HbA1c <5.7%	Percentage of participants who achieve HbA1c <5.7%	Week 72
Secondary	Change From Baseline in Fasting Glucose	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Baseline HbA1c Group (<=8.5%, >8.5%) + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Secondary	Change From Baseline in Waist Circumference	LSMean calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Secondary	Percent Change From Baseline in Total Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Results are reported as model-based estimates and standard error (SE) from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Percent Change From Baseline in Low Density Lipoprotein (LDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Percent Change From Baseline in High Density Lipoprotein (HDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Percent Change From Baseline in Very Low Density Lipoprotein (VLDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Percent Change From Baseline in Triglycerides (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Percent Change From Baseline in Non-High Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Tirzepatide 10 mg and 15 mg)	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Percent Change From Baseline in Free Fatty Acids (Pooled Doses of 10 mg and 15 mg Tirzepatide)	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of 10 mg and 15 mg Tirzepatide)	LSMean was calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Secondary	Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of 10 mg and 15 mg Tirzepatide)	LSMean was calculated using MMRM model for post-baseline measures: Variable = Baseline + Analysis Country + Sex + Type of AHM Used at Randomization + Treatment + Time + Treatment*Time (Type III sum of squares).	Baseline, Week 72
Secondary	Percent Change From Baseline in Fasting Insulin	Results are reported as model-based estimates and SE from MMRM analysis using log transformation.	Baseline, Week 72
Secondary	Change From Baseline in Short Form 36 Health Survey Version 2 (SF-36v2) Acute Form Physical Functioning Domain Score	The SF-36v2 acute, 1-week recall version is a 36-item, generic, patient-administered measure designed to assess the following 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The Physical-Functioning domain assesses limitations due to health "now" while the remaining domains assess functioning "in the past week." Each domain is scored individually and information from these 8 domains are further aggregated into 2 health-component summary scores: Physical-Component Summary and Mental-Component Summary. Items are answered on Likert scales of varying lengths (3-, 5-, or 6- point scales).The summary scores range from 0 to 100, with higher scores indicating better levels of function and/or better health.	Baseline, Week 72
Secondary	Change From Baseline in Impact of Weight on Quality of Life-Lite-Clinical Trials Version (IWQOL Lite-CT) Physical Function Composite Score	The IWQOL-Lite-CT is a 20-item, obesity-specific patient reported outcome (PRO) instrument developed for use in obesity clinical trials. It assesses 2 primary domains of obesity-related health-related quality of life (HRQoL): physical (7 items), and psychosocial (13 items). A 5-item subset of the physical domain, the physical-function composite is also supported. Items in the physical-function composite describe physical impacts related to general and specific physical activities. All items in the physical domain are rated on either a 5-point frequency ("never" to "always") scale or a 5-point truth ("not at all true" to "completely true") scale. Total score of IWQOL-Lite-CT composite ranges from 0 to 100, with higher scores reflecting better quality of life.	Baseline, Week 72
Secondary	Population Pharmacokinetics (PopPK): Steady State Area Under the Concentration Curve (AUC) of Tirzepatide	Each participant was assigned via the Interactive Web Response System (IWRS) to one of the sampling PK time windows of 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose. The steady state AUC was evaluated using Population PK modeling.	Week 8, 16, 36: 1 to 24 hours, 24 to 96 hours, or 120 to 168 hours postdose

External Links

•   A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Who Have Obesity or Are Overweight (SURMOUNT-2)