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A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes Not Controlled With Diet and Exercise Alone

Phase 3
Completed
Conditions
Type 2 Diabetes Mellitus
Interventions
Drug: Placebo
Registration Number
NCT03954834
Lead Sponsor
Eli Lilly and Company
Brief Summary

The goal for this study is to evaluate the efficacy and safety of tirzepatide versus placebo in participants with type 2 diabetes not under control with diet and exercise alone. The study will last approximately 47 weeks and may include about 15 visits.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
478
Inclusion Criteria
  • Have been diagnosed with type 2 diabetes mellitus (T2DM).
  • Are naïve to diabetes injectable therapies and have not used any oral antihyperglycemic medications (OAMs) during the 3 months preceding screening.
  • Have HbA1c between ≥7.0% and ≤9.5%.
  • Be of stable weight (± 5%) for at least 3 months before screening.
  • Have a BMI ≥23 kilograms per meter squared (kg/m²) at screening.
Exclusion Criteria
  • Have type 1 diabetes mellitus.
  • Have had chronic or acute pancreatitis any time prior to study entry.
  • Have proliferative diabetic retinopathy or diabetic maculopathy or nonproliferative diabetic retinopathy requiring acute treatment.
  • Have disorders associated with slowed emptying of the stomach, or have had any stomach surgeries for the purpose of weight loss.
  • Have an estimated glomerular filtration rate <30 mL/minute/1.73 m².
  • Have had a heart attack, stroke, or hospitalization for congestive heart failure in the past 2 months.
  • Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2.
  • Have been taking weight loss drugs, including over-the-counter medications during the last 3 months.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
PlaceboPlaceboParticipants received placebo as subcutaneous injection once a week.
15 mg TirzepatideTirzepatideParticipants received 15mg of tirzepatide as subcutaneous injection once a week.
5 mg TirzepatideTirzepatideParticipants received 5 milligrams (mg) of tirzepatide as subcutaneous injection once a week.
10 mg TirzepatideTirzepatideParticipants received 10mg of tirzepatide as subcutaneous injection once a week.
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Hemoglobin A1c (HbA1c)Baseline, Week 40

HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured primarily to identify average plasma glucose concentration over prolonged periods of time. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Prior Use of oral antihyperglycemic medication (OAM) (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants With HbA1c Target Value of <5.7%Week 40

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Mean Change From Baseline in Daily Average 7-Point Self-Monitored Blood Glucose (SMBG) ValuesBaseline, Week 40

The self-monitored plasma glucose (SMBG) data were collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Postmeal, Midday Premeal, Midday 2-hour Postmeal, Evening Premeal, Evening 2-hour Postmeal and Bedtime. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Rate of Hypoglycemia With Blood Glucose <54 Milligram/Deciliter (mg/dL) [<3.0 Millimole/Liter (mmol/L)] or Severe HypoglycemiaBaseline through end of safety follow-up (up to week 44)

The hypoglycemia events were defined by participant reported events with blood glucose \<54mg/dL) (\<3.0 mmol/L\] or severe hypoglycemia. Severe hypoglycemia is defined as an episode with severe cognitive impairment requiring the assistance of another person to actively administer carbohydrate, glucagon, or other resuscitative actions. These episodes may be associated with sufficient neuroglycopenia to induce seizure or coma. The rate of postbaseline hypoglycemia was estimated by negative binomial model: number of episodes = Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment, with log (exposure in days/365.25) as an offset variable.

Percentage of Participants Who Achieved Weight Loss ≥5%Week 40

Percentage of Participants who Achieved Weight Loss ≥5%.

Change From Baseline in Body WeightBaseline, Week 40

Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Percentage of Participants With HbA1c Target Value of <7%Week 40

Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time.

Change From Baseline in Fasting Serum GlucoseBaseline, Week 40

Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. Least Squares (LS) mean was determined by mixed-model repeated measures (MMRM) model with Baseline + Pooled Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Prior Use of OAM (Yes, No) + Treatment + Time + Treatment\*Time (Type III sum of squares).

Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of TirzepatideWeek 7, 15 and 23

Pharmacokinetics (PK): Steady State Area Under the Concentration Time Curve (AUC) of Tirzepatide. AUC is a combined measure obtained from Week 7, 15 and 23, and a single averaged measure of AUC was reported.

Trial Locations

Locations (50)

BSES Municipal General Hsptl

🇮🇳

Mumbai, Maharashtra, India

Meiwa Hospital

🇯🇵

Chiyodaku, Tokyo, Japan

Tokyo Center Clinic

🇯🇵

Chuo-ku, Tokyo, Japan

Sato Naika Clinic

🇯🇵

Ota-ku, Tokyo, Japan

IHL Shinagawa East One Medical Clinic

🇯🇵

Minato-ku, Tokyo, Japan

Lifepoint Multispecialty Hsptl

🇮🇳

Wakad, Pune, India

GCM Medical Group PSC

🇵🇷

San Juan, Puerto Rico

Ramdevrao Hospital

🇮🇳

Hyderabad, Telangana, India

Suncoast Research Group, LLC

🇺🇸

Miami, Florida, United States

Encore Medical Research, LLC

🇺🇸

Hollywood, Florida, United States

Aventiv Research

🇺🇸

Columbus, Ohio, United States

Capital Clinical Research Center

🇺🇸

Olympia, Washington, United States

Southern California Dermatology

🇺🇸

Santa Ana, California, United States

Sky Clinical Research Network

🇺🇸

Atlanta, Georgia, United States

Clinical Research of South Florida

🇺🇸

Coral Gables, Florida, United States

Gandhi Hospital

🇮🇳

Telangana, India

Valley Clinical Trials, Inc.

🇺🇸

Northridge, California, United States

Agile Clinical Research Trials

🇺🇸

Atlanta, Georgia, United States

Preferred Primary Care Physicians

🇺🇸

Uniontown, Pennsylvania, United States

StudyMetrix Research, LLC

🇺🇸

Saint Peters, Missouri, United States

Minamiakatsuka Clinic

🇯🇵

Mito, Ibaraki, Japan

Cotton O'Neil Clinic

🇺🇸

Topeka, Kansas, United States

Bangalore Medical College and Research Institute

🇮🇳

Bangalore, Karnataka, India

Tsuruma Kaneshiro Diabetes Clinic

🇯🇵

Yamato, Kanagawa, Japan

Takai Naika Clinic

🇯🇵

Kamakura, Kanagawa, Japan

M S Ramaiah Medical College Hospital

🇮🇳

Bangalore, Karnataka, India

Unidad Medica para la Salud Integral (UMSI)

🇲🇽

Monterrey, Nuevo León, Mexico

Intend Research

🇺🇸

Norman, Oklahoma, United States

South Florida Wellness & Clinical Research Institute

🇺🇸

Margate, Florida, United States

Axcess Medical Research

🇺🇸

Loxahatchee Groves, Florida, United States

Consano Clinical Research

🇺🇸

Shavano Park, Texas, United States

National Research Institute

🇺🇸

Panorama City, California, United States

Dallas Diabetes Endocrine Center

🇺🇸

Dallas, Texas, United States

Rockwood Clinic Research Center

🇺🇸

Spokane, Washington, United States

Dr. Jivraj Mehta Smarak Health Foundation

🇮🇳

Ahmedabad, Gujarat, India

Tokyo-Eki Center-building Clinic

🇯🇵

Chuo-ku, Tokyo, Japan

Clinical Research Puerto Rico, Inc.

🇵🇷

San Juan, Puerto Rico

Investigacion en Salud y Metabolismo S.C

🇲🇽

Chihuahua, Mexico

Catalina Research Institute, LLC

🇺🇸

Montclair, California, United States

Clinical Research Professionals

🇺🇸

Chesterfield, Missouri, United States

Yokohama Minoru Clinic

🇯🇵

Yokohama, Kanagawa, Japan

Heritage Valley Medical Group, Inc.

🇺🇸

Beaver, Pennsylvania, United States

The Corvallis Clinic P.C.

🇺🇸

Corvallis, Oregon, United States

Takatsuki Red Cross Hospital

🇯🇵

Takatsuki, Osaka, Japan

Family Medical Associates

🇺🇸

Levittown, Pennsylvania, United States

Centro de Estudios de Investigacion Metabolicos y Cardiovasc

🇲🇽

Madero, Tamaulipas, Mexico

Ruby Hall Clinic and Grant Medical Foundation

🇮🇳

Pune, Maharashtra, India

Vijay Vallabh Hospital

🇮🇳

Virar, Maharashtra, India

Hospital Universitario UANL

🇲🇽

Monterrey, Nuevo León, Mexico

Clinical Trials of Texas, Inc.

🇺🇸

San Antonio, Texas, United States

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