A Study of Tirzepatide (LY3298176) in Participants With Type 2 Diabetes on Metformin With or Without Sulfonylurea (SURPASS-AP-Combo)

Type 2 Diabetes Clinical Trial

Official title:

A Randomized, Phase 3, Open-label Trial Comparing the Effect of Tirzepatide Once Weekly Versus Titrated Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes on Metformin With or Without a Sulfonylurea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04093752
• Other study ID #: 17210
• Secondary ID: I8F-MC-GPHO
• Status: Completed
• Phase: Phase 3
• Start date: December 9, 2019
• Est. completion date: November 24, 2021

Study information

• Verified date: December 2022
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 917
• Est. completion date: November 24, 2021
• Est. primary completion date: November 1, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Tirzepatide
Administered SC
• Insulin Glargine
Administered SC

Locations

Country	Name	City	State
Australia	Paratus Clinical Research Western Sydney	Blacktown	New South Wales
Australia	Barwon Health - The Geelong Hospital	Geelong	Victoria
Australia	Paratus Clinical Research Central Coast	Kanwal	New South Wales
Australia	Core Research Group	Milton	Queensland
Australia	Holdsworth House Medical Practice	Sydney	New South Wales
Australia	Illawarra Shoalhaven Local Health District	Wollongong	New South Wales
Australia	Adelaide Medical Solutions	Woodville South
China	Bao Tou Central Hospital	Bao Tou	Inner Mongolia
China	Beijing Peking Union Medical College Hospital	Beijing
China	Beijing Pinggu District Hospital	Beijing
China	Beijing Tsinghua Changgung Hospital	Beijing
China	Peking University People's Hospital	Beijing	Beijing
China	Cangzhou People's Hospital	Cangzhou	Hebei
China	The First Hospital of Jilin University	Changchun	Jilin
China	Changzhou No.2 People's Hospital	Changzhou	Jiangsu
China	Chengdu Fifth People's Hospital	Chengdu	Sichuan
China	West China Hospital Sichuan University	Chengdu	Sichuan
China	Chongqing General Hospital	Chongqing	Yuzhong District
China	Dalian University - The Affiliated Zhongshan Hospital	Dalian	Liaoning
China	The Fourth Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Hebei Medical University	Hengshui Shi	Hebei
China	Huizhou Municipal Central Hospital	Huizhou	Guangdong
China	Huzhou Central Hospital	Huzhou	Zhejiang
China	Jinan Central Hospital	Jinan	Shandong
China	The First Affiliated Hospital of Henan University of Science &Technology	Luoyang	Henan
China	The Third Hospital of Nanchang	Nanchang	Jiangxi
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 First Hospital of Nanjing	Nanjing	Jiangsu
China	The Second Affiliated Hospital of Nanjing Medical University	Nanjing	Jiangsu
China	Zhongda Hospital Southeast University	Nanjing	Jiangsu
China	Pingxiang People's Hospital	Pingxiang
China	Qingdao Central Hospital	Qingdao	Shandong
China	Shanghai 6th people's hospital	Shanghai	Shanghai
China	Shanghai Putuo District Center Hospital	Shanghai
China	Shaoxing People's Hospital	Shaoxing	Zhejiang
China	Shengjing Hospital of China Medical University	Shenyang	Liaoning
China	Suzhou Municipal Hospital	Suzhou	Jiangsu
China	The First Affiliated Hospital of Soochow University	Suzhou	Jiangsu
China	1st affiliated Hospital of Shanxi Medical University	Tai Yuan	Shan XI
China	Tianjin Medical University General Hospital	Tianjin	Tianjin
China	Tianjin People's Hospital	Tianjin
China	Chongqing Three Gorges Central Hospital	Wanzhou	Wanzhou
China	Wuxi People's Hospital	Wuxi	Jiangsu
China	The First Affiliated Hospital of Xi'an Medical University	XI 'an	Shanxi
China	First Affiliated Hospital of Xi'an Jiaotong University	Xi'an	Shaanxi
China	The First People's Hospital of Yueyang	Yueyang	Hunan
China	The Second Affiliated Hospital of Zhengzhou University	Zhengzhou Shi	Henan
China	Affiliated Hospital of Jiangsu University	Zhenjiang	Jiangsu
China	The Fourth People's Hospital of Zigong City	Zigong
India	Fortis Hospital	Delhi
India	Apollo Gleneagles Hospitals Kolkata	Kolkata	West Bengal
India	BSES Municipal General Hsptl	Mumbai	Maharashtra
India	King Edward Memorial Hospital and Research Center	Mumbai	Maharashtra
Korea, Republic of	Korea University Ansan Hospital	Ansan-si
Korea, Republic of	Bucheon St. Mary's Hospital	Bucheon,	Gyeonggi-do
Korea, Republic of	Keimyung University Dongsan Hospital	Daegu	Taegu-Kwangyokshi
Korea, Republic of	Yonsei University Wonju Severance Christian Hospital	Gangwon-do	Korea
Korea, Republic of	Hanyang University Guri Hospital	Guri-si	Gyeonggido
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam	Geonggi-do
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Hallym University Kangnam Sacred Heart Hospital	Seoul
Korea, Republic of	Inje University Sanggye Paik Hospital	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Korea University Anam Hospital	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Kyung Hee University Hospital	Seoul	Gangdong-gu
Korea, Republic of	Severance Hospital	Seoul
Korea, Republic of	Ulsan University Hospital	Ulsan	Korea

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

Australia,  China,  India,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean Change From Baseline in Hemoglobin A1c (HbA1c) (10 mg and 15 mg)	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).	Baseline, Week 40
Secondary	Mean Change From Baseline in HbA1c (5 mg)	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).	Baseline, Week 40
Secondary	Mean Change From Baseline in Body Weight	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.	Baseline, Week 40
Secondary	Percentage of Participants Achieving an HbA1c Target Value of <7.0%	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.	Week 40
Secondary	Percentage of Participants Achieving an HbA1c Target Value of <5.7%	HbA1c is the glycosylated fraction of hemoglobin A. Imputed data includes observed value and imputed value if endpoint measure is missing.	Week 40
Secondary	Mean Change From Baseline in Fasting Serum Glucose	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.	Baseline, Week 40
Secondary	Mean Change in Daily Glucose Average From Baseline in 7-Point Self-Monitored Blood Glucose (SMBG) Values	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.	Baseline, Week 40
Secondary	Percentage of Participants Who Achieved Weight Loss =5%	Imputed data includes observed value and imputed value if endpoint measure is missing.	Week 40
Secondary	Diabetes Treatment Satisfaction as Measured by the Diabetes Treatment Satisfaction Questionnaire, Change Version (DTSQc) Hyperglycemia, Hypoglycemia and Treatment Satisfaction Score	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.	Baseline, Week 40
Secondary	Rate of Hypoglycemia With Blood Glucose < 54 mg/dL or Severe Hypoglycemia	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.	Baseline through end of safety follow-up (Up To Week 44)