A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes on Metformin With or Without Sulfonylurea (SURPASS-AP-Combo)
- Registration Number
- NCT04093752
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The main reason for this study is to compare the study drug tirzepatide to insulin glargine in participants with type 2 diabetes on metformin with or without a sulfonylurea.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 917
- Type 2 diabetes mellitus
- Treated with stable metformin with or without a sulfonylurea (metformin ≥1000 milligrams/day; sulfonylurea should be at least half the maximum dose) for at least 2 months
- Are insulin-naive (except for the use of insulin for treatment of gestational diabetes or short-term use [≤14 consecutive days] for acute conditions)
- HbA1c ≥7.5% to ≤11.0% at screening
- Stable weight (±5%) ≥3 months, and agree to not initiate a diet and/or exercise program during the study with the intent of reducing body weight other than the lifestyle and dietary measures for diabetes treatment
- Body mass Index (BMI) ≥23 kilograms per meter squared
- Type 1 diabetes mellitus
- Have history of chronic or acute pancreatitis
- Have history of proliferative diabetic retinopathy; or diabetic maculopathy; or non-proliferative diabetic retinopathy that requires acute treatment
- Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months
- Have a history of ketoacidosis or hyperosmolar state/coma
- Have a known clinically significant gastric emptying abnormality, have undergone or plan to have during the course of the study, or chronically take drugs that directly affect GI motility
- Have acute myocardial infarction (MI), stroke or hospitalization due to congestive heart failure (CHF) within 2 months
- Have family or personal history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN-2)
- Have been treated with prescription drugs that promote weight loss or similar other body weight loss medications including over the counter (OTC) within 3 months
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 10 mg Tirzepatide Tirzepatide Participants received 10 mg tirzepatide administered SC QW. 15 mg Tirzepatide Tirzepatide Participants received 15 mg tirzepatide administered SC QW. 5 mg Tirzepatide Tirzepatide Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW). Insulin Glargine Insulin Glargine Participants received insulin glargine administered once daily (QD) SC. The starting dose of insulin glargine was 6 Insulin Units (IU)/day at bedtime, titrated to a fasting blood glucose (FBG) between 72-100 milligrams per Deciliter (mg/dL), following a treat-to-target (TTT) algorithm.
- Primary Outcome Measures
Name Time Method Mean Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg) 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 covariates Baseline + Country + Baseline Oral Antihyperglycemic Medication (OAM) Use (Metformin (Met), Met plus Sulfonylurea (SU)) + Treatment + Time + Treatment\*Time (Type III sum of squares).
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving an HbA1c Target Value of <7.0% Week 40 HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Imputed data includes observed value and imputed value if endpoint measure is missing.
Mean Change From Baseline in Body Weight Baseline, Week 40 LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.
Mean Change From Baseline in HbA1c (5 mg) 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. LS mean was determined by MMRM model with covariates Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Treatment + Time + Treatment\*Time (Type III sum of squares).
Percentage of Participants Achieving an HbA1c Target Value of <5.7% Week 40 HbA1c is the glycosylated fraction of hemoglobin A. Imputed data includes observed value and imputed value if endpoint measure is missing.
Mean Change in Daily Glucose Average From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values Baseline, Week 40 The SMBG data was collected at the following 7 time points: Morning Premeal - Fasting, Morning 2-hour Post-meal, Midday Premeal, Midday 2-hour Post-meal, Evening Premeal, Evening 2-hour Post-meal and Bedtime. LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.
Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score Baseline, Week 40 DTSQc, an 8-item questionnaire, assesses relative change in treatment satisfaction perceived frequency of hyperglycemia, and perceived frequency of hypoglycemia from baseline to week 40 or early termination. The treatment satisfaction score ranges from -18 to 18 where the higher the score the greater the improvement in satisfaction with treatment. The lower the score the greater the deterioration in satisfaction with treatment. The hyperglycemia and hypoglycemia scores range from -3 to 3 where negative scores indicate fewer problems with blood glucose levels and positive scores indicate more problems than before. LS mean was determined by ANCOVA model for endpoint measures with Baseline + Country + Baseline HbA1c Group (\<=8.5%, \>8.5%) + Baseline OAM Use (Met, Met plus SU) + Treatment (Type III sum of squares) as covariates.
Mean Change From Baseline in Fasting Serum Glucose Baseline, Week 40 Fasting serum glucose (FSG) is a test to determine sugar levels in serum sample after an overnight fast. LS mean was determined by MMRM model with Baseline + Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment + Time + Treatment\*Time (Type III sum of squares) as covariates.
Percentage of Participants Who Achieved Weight Loss ≥5% Week 40 Imputed data includes observed value and imputed value if endpoint measure is missing.
Rate of Hypoglycemia With Blood Glucose < 54 mg/dL or Severe Hypoglycemia Baseline through end of safety follow-up (Up To Week 44) The hypoglycemia events were defined by participant reported events with blood glucose \< 54 mg/dL \[\<3.0 Millimole per Liter (mmol/L)\] 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 post-baseline hypoglycemia was estimated by negative binomial model: Number of episodes = Country + Baseline OAM Use (Met, Met plus SU) + Baseline HbA1c Group (\<= 8.5%, \>8.5%) + Treatment, with log (exposure in days/365.25) as an offset variable.
Trial Locations
- Locations (67)
Huizhou Municipal Central Hospital
🇨🇳Huizhou, Guangdong, China
Hebei Medical University
🇨🇳Hengshui Shi, Hebei, China
Illawarra Shoalhaven Local Health District
🇦🇺Wollongong, New South Wales, Australia
Paratus Clinical Research Western Sydney
🇦🇺Blacktown, New South Wales, Australia
Paratus Clinical Research Central Coast
🇦🇺Kanwal, New South Wales, Australia
Bao Tou Central Hospital
🇨🇳Bao Tou, Inner Mongolia, China
Suzhou Municipal Hospital
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Adelaide Medical Solutions
🇦🇺Woodville South, Australia
The Second Affiliated Hospital of Zhengzhou University
🇨🇳Zhengzhou Shi, Henan, China
The First People's Hospital of Yueyang
🇨🇳Yueyang, Hunan, China
Barwon Health - The Geelong Hospital
🇦🇺Geelong, Victoria, Australia
Peking University People's Hospital
🇨🇳Beijing, Beijing, China
Tianjin People's Hospital
🇨🇳Tianjin, China
Core Research Group
🇦🇺Milton, Queensland, Australia
Bucheon St. Mary's Hospital
🇰🇷Bucheon,, Gyeonggi-do, Korea, Republic of
The First Affiliated Hospital of Xi'an Medical University
🇨🇳XI 'an, Shanxi, China
Seoul National University Bundang Hospital
🇰🇷Seongnam, Geonggi-do, Korea, Republic of
Yonsei University Wonju Severance Christian Hospital
🇰🇷Gangwon-do, Korea, Korea, Republic of
Korea University Anam Hospital
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Hallym University Kangnam Sacred Heart Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital
🇰🇷Seoul, Korea, Republic of
Inje University Sanggye Paik Hospital
🇰🇷Seoul, Seoul-teukbyeolsi, Korea, Republic of
Korea University Ansan Hospital
🇰🇷Ansan-si, Korea, Republic of
Holdsworth House Medical Practice
🇦🇺Sydney, New South Wales, Australia
Wuxi People's Hospital
🇨🇳Wuxi, Jiangsu, China
Zhongda Hospital Southeast University
🇨🇳Nanjing, Jiangsu, China
The First Hospital of Jilin University
🇨🇳Changchun, Jilin, China
Keimyung University Dongsan Hospital
🇰🇷Daegu, Taegu-Kwangyǒkshi, Korea, Republic of
Hanyang University Guri Hospital
🇰🇷Guri-si, Gyeonggido, Korea, Republic of
Cangzhou People's Hospital
🇨🇳Cangzhou, Hebei, China
The Fourth Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The First Affiliated Hospital of Henan University of Science &Technology
🇨🇳Luoyang, Henan, China
Changzhou No.2 People's Hospital
🇨🇳Changzhou, Jiangsu, China
The First Hospital of Nanjing
🇨🇳Nanjing, Jiangsu, China
Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
🇨🇳Nanjing, Jiangsu, China
Nanjing Medical University - Nanjing Jiangning Hospital
🇨🇳Nanjing, Jiangsu, China
The Second Affiliated Hospital of Nanjing Medical University
🇨🇳Nanjing, Jiangsu, China
Affiliated Hospital of Jiangsu University
🇨🇳Zhenjiang, Jiangsu, China
The Third Hospital of Nanchang
🇨🇳Nanchang, Jiangxi, China
First Affiliated Hospital of Xi'an Jiaotong University
🇨🇳Xi'an, Shaanxi, China
Shengjing Hospital of China Medical University
🇨🇳Shenyang, Liaoning, China
Dalian University - The Affiliated Zhongshan Hospital
🇨🇳Dalian, Liaoning, China
1st affiliated Hospital of Shanxi Medical University
🇨🇳Tai Yuan, Shan XI, China
Jinan Central Hospital
🇨🇳Jinan, Shandong, China
Shanghai 6th people's hospital
🇨🇳Shanghai, Shanghai, China
Qingdao Central Hospital
🇨🇳Qingdao, Shandong, China
West China Hospital Sichuan University
🇨🇳Chengdu, Sichuan, China
Tianjin Medical University General Hospital
🇨🇳Tianjin, Tianjin, China
Chengdu Fifth People's Hospital
🇨🇳Chengdu, Sichuan, China
Chongqing Three Gorges Central Hospital
🇨🇳Wanzhou, Wanzhou, China
Huzhou Central Hospital
🇨🇳Huzhou, Zhejiang, China
Chongqing General Hospital
🇨🇳Chongqing, Yuzhong District, China
Beijing Peking Union Medical College Hospital
🇨🇳Beijing, China
Shaoxing People's Hospital
🇨🇳Shaoxing, Zhejiang, China
Beijing Pinggu District Hospital
🇨🇳Beijing, China
Beijing Tsinghua Changgung Hospital
🇨🇳Beijing, China
Pingxiang People's Hospital
🇨🇳Pingxiang, China
Shanghai Putuo District Center Hospital
🇨🇳Shanghai, China
King Edward Memorial Hospital and Research Center
🇮🇳Mumbai, Maharashtra, India
BSES Municipal General Hsptl
🇮🇳Mumbai, Maharashtra, India
The Fourth People's Hospital of Zigong City
🇨🇳Zigong, China
Apollo Gleneagles Hospitals Kolkata
🇮🇳Kolkata, West Bengal, India
Fortis Hospital
🇮🇳Delhi, India
Kyung Hee University Hospital
🇰🇷Seoul, Gangdong-gu, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Ulsan University Hospital
🇰🇷Ulsan, Korea, Korea, Republic of