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

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)

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).

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight; Type 2 Diabetes
• Intervention / Treatment: Drug: Tirzepatide; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 938
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Santiago del Estero, Argentina, 4200
    • Sanatorio Norte
  • Buenos Aires
    • Ciudad Autonoma de Buenos Aire, Buenos Aires, Argentina, C1405BUB
      • Consultorio de Investigacion Clinica EMO SRL
    • Ciudad Autónoma de Buenos Aire, Buenos Aires, Argentina, 1056
      • Centro de Investigaciones Metabólicas (CINME)
    • Mar del Plata, Buenos Aires, Argentina, 7600
      • Instituto de Investigaciones Clínicas Mar del Plata
    • San Nicolas, Buenos Aires, Argentina, 2900
      • Go Centro Medico San Nicolás
  • Ciudad Autónoma De Buenos Aire
    • Buenos Aires, Ciudad Autónoma De Buenos Aire, Argentina, C1120AAC
      • Centro Medico Viamonte
    • Caba, Ciudad Autónoma De Buenos Aire, Argentina, C1061AAS
      • CIPREC
  • Tucumán
    • SAN M. DE Tucuman, Tucumán, Argentina, T4000AXL
      • Centro de Investigaciones Medicas Tucuman
• Brazil
  • São Paulo, Brazil, 04266-010
    • CEPIC - Centro Paulista de Investigacao Clinica
  • Ceará
    • Fortaleza, Ceará, Brazil, 60430-350
      • Private Practice - Dr.Miguel N. Hissa
  • São Paulo
    • Campinas, São Paulo, Brazil, 13010-001
      • Loema Instituto de Pesquisa Clinica
    • Campinas, São Paulo, Brazil, 13060-080
      • Instituto de Pesquisa Clínica de Campinas
    • Jaú, São Paulo, Brazil, 17201130
      • CECIP - Centro de Estudos do Interior Paulista
    • Sao Paulo, São Paulo, Brazil, 01228-200
      • CPCLIN
• India
  • Karnataka
    • Bangalore, Karnataka, India, 560092
      • Life Care Hospital and Research Centre
  • West Bengal
    • Kolkata, West Bengal, India, 700064
      • ILS Hospitals
• Japan
  • Osaka, Japan, 530-0001
    • AMC Nishiumeda Clinic
  • Kanagawa
    • Yamato-shi, Kanagawa, Japan, 242-0004
      • Medical Corporation Yuga Tsuruma Kaneshiro Diabetes Clinic
  • Osaka
    • Suita-shi, Osaka, Japan, 565-0853
      • Medical Corporation Heishinkai OCROM Clinic
  • Tokyo
    • Ootaku, Tokyo, Japan, 143-0015
      • Medical Corporation Sato Medical clinic
• Puerto Rico
  • Caguas, Puerto Rico, 00725
    • Centro de Endocrinologia y Nutricion
  • San Juan, Puerto Rico, 00909
    • Latin Clinical Trial Center
  • San Juan, Puerto Rico, 917
    • GCM Medical Group, PSC - Hato Rey Site
• Russian Federation
  • Smolensk, Russian Federation, 214019
    • Smolensk State Medical University
  • Moskva
    • Moscow, Moskva, Russian Federation, 117036
      • Endocrinology Research Center of Rosmedtechnologies
    • Moscow, Moskva, Russian Federation, 125284
      • Russian Medical Academy of Postgraduate Education
  • Sankt-Pete
    • Saint Petersburg, Sankt-Pete, Russian Federation, 195257
      • Saint-Petersburg City Hospital of Saint Elizabeth
• Taiwan
  • Taichung, Taiwan, 402
    • Chung Shan Medical University Hospital
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 704
    • National Cheng-Kung Uni. Hosp.
  • Changhua
    • Changhua County, Changhua, Taiwan, 50006
      • ChangHua Christian Hospital
  • Tainan
    • Tainan City, Tainan, Taiwan, 71004
      • Chi Mei Medical Center
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama - Department of Nutrition Sciences
  • Arkansas
    • Little Rock, Arkansas, United States, 72205
      • KLR Business Group, Inc. dba Arkansas Clinical Research
  • California
    • Huntington Park, California, United States, 90255
      • Velocity Clinical Research, Huntington Park
    • Los Angeles, California, United States, 90057
      • Velocity Clinical Research, Westlake
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Spring Valley, California, United States, 91978
      • Encompass Clinical Research
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
  • Florida
    • Cooper City, Florida, United States, 33024
      • ALL Medical Research, LLC
    • Fleming Island, Florida, United States, 32003
      • Northeast Research Institute (NERI)
    • Miami, Florida, United States, 33165
      • New Horizon Research Center
    • Ocoee, Florida, United States, 34761
      • West Orange Endocrinology
    • West Palm Beach, Florida, United States, 33401
      • Metabolic Research Institute, Inc.
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Emory University School of Medicine- Grady Campus
    • Macon, Georgia, United States, 31210
      • East Coast Institute for Research, LLC
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pacific Diabetes & Endocrine Center
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Elite Clinical Trials
    • Idaho Falls, Idaho, United States, 83404
      • Rocky Mountain Clinical Research
  • Indiana
    • Greenfield, Indiana, United States, 46140
      • American Health Network of Indiana, LLC - Greenfield
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Cotton O'Neil Clinical Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21229
      • Maryland Cardiovascular Specialists
    • Oxon Hill, Maryland, United States, 20745
      • MD Medical Research
  • Massachusetts
    • Fall River, Massachusetts, United States, 02721
      • NECCR PrimaCare Research
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
  • Montana
    • Kalispell, Montana, United States, 59901
      • Logan Health Research
  • New Jersey
    • Trenton, New Jersey, United States, 08611
      • Premier Research
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27514
      • University of North Carolina Medical Center
    • Greensboro, North Carolina, United States, 27408
      • PharmQuest
    • Winston-Salem, North Carolina, United States, 27157
      • Wake Forest University Baptist Medical Center (WFUBMC)
  • Ohio
    • Cleveland, Ohio, United States, 44122
      • Velocity Clinical Research, Cleveland
    • Dublin, Ohio, United States, 43016
      • Aventiv Research
  • Oregon
    • Corvallis, Oregon, United States, 97330
      • The Corvallis Clinic, P.C.
  • Pennsylvania
    • Uniontown, Pennsylvania, United States, 15401
      • Preferred Primary Care Physicians
  • Rhode Island
    • Warwick, Rhode Island, United States, 02886
      • Center for Neurosciences
  • South Carolina
    • Greenville, South Carolina, United States, 29607
      • Tribe Clinical Research, LLC
  • Texas
    • Austin, Texas, United States, 78749
      • Texas Diabetes & Endocrinology, P.A.
    • Dallas, Texas, United States, 75230
      • Dallas Diabetes Research Center
    • Fort Worth, Texas, United States, 76132
      • Diabetes and Thyroid Center of Fort Worth
    • Houston, Texas, United States, 77040
      • Juno Research
    • Houston, Texas, United States, 77079
      • Endocrine Ips, Pllc
  • Virginia
    • Newport News, Virginia, United States, 23606
      • Health Research of Hampton Roads, Inc.
  • Washington
    • Renton, Washington, United States, 98057
      • Rainier Clinical Research Center
  • Wisconsin
    • Kenosha, Wisconsin, United States, 53144
      • Clinical Investigation Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 10 milligrams (mg) Tirzepatide; 10 mg Tirzepatide administered subcutaneously (SC) once weekly (QW)	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 15 mg Tirzepatide; 15 mg Tirzepatide administered SC QW	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo; Placebo administered SC QW	Other: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieve ≥10% Body Weight Reduction From Baseline	Percentage of participants who achieve ≥10% body weight reduction from baseline	Week 72
Percentage of Participants Who Achieve ≥15% Body Weight Reduction From Baseline	Percentage of participants who achieve ≥15% body weight reduction from baseline	Week 72
Percentage of Participants Who Achieve ≥20% Body Weight Reduction From Baseline	Percentage of participants who achieve ≥20% body weight reduction from baseline	Week 72
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
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
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
Percentage of Participants Who Achieve HbA1c <7%	Percentage of participants who achieve HbA1c <7%	Week 72
Percentage of Participants Who Achieve HbA1c ≤6.5%	Percentage of participants who achieve HbA1c ≤6.5%	Week 72
Percentage of Participants Who Achieve HbA1c <5.7%	Percentage of participants who achieve HbA1c <5.7%	Week 72
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Eli Lilly and Company
• Investigators: Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): March 29, 2021
• Primary Completion (Actual): March 16, 2023
• Study Completion (Actual): April 10, 2023

Study Registration Dates

• First Submitted: December 1, 2020
• First Submitted That Met QC Criteria: December 1, 2020
• First Posted (Actual): December 7, 2020

Study Record Updates

• Last Update Posted (Actual): April 8, 2024
• Last Update Submitted That Met QC Criteria: March 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Metabolism and Nutrition Disorder
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Overnutrition; Nutrition Disorders; Body Weight; Diabetes Mellitus; Diabetes Mellitus, Type 2; Obesity; Overweight; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 17245; I8F-MC-GPHL (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.

IPD Sharing Time Frame

Time Frame:

Data are available 6 months after the primary publication or approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting.

• IPD Sharing Access Criteria: A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No