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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes
• Intervention / Treatment: Drug: Tirzepatide; Drug: Insulin Glargine

• Study Type: Interventional
• Enrollment (Actual): 917
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Woodville South, Australia, 5011
    • Adelaide Medical Solutions
  • New South Wales
    • Blacktown, New South Wales, Australia, 2148
      • Paratus Clinical Research Western Sydney
    • Kanwal, New South Wales, Australia, 2259
      • Paratus Clinical Research Central Coast
    • Sydney, New South Wales, Australia, 2010
      • Holdsworth House Medical Practice
    • Wollongong, New South Wales, Australia, 2500
      • Illawarra Shoalhaven Local Health District
  • Queensland
    • Milton, Queensland, Australia, 4064
      • Core Research Group
  • Victoria
    • Geelong, Victoria, Australia, 3220
      • Barwon Health - The Geelong Hospital
• China
  • Beijing, China, 101200
    • Beijing Pinggu District Hospital
  • Beijing, China, 100730
    • Beijing Peking Union Medical College Hospital
  • Beijing, China, 102202
    • Beijing Tsinghua Changgung Hospital
  • Pingxiang, China, 337000
    • Pingxiang People's Hospital
  • Shanghai, China, 200062
    • Shanghai Putuo District Center Hospital
  • Tianjin, China, 300121
    • Tianjin People's Hospital
  • Zigong, China
    • The Fourth People's Hospital of Zigong City
  • Beijing
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
  • Guangdong
    • Huizhou, Guangdong, China, 516001
      • Huizhou Municipal Central Hospital
  • Hebei
    • Cangzhou, Hebei, China, 061600
      • Cangzhou People's Hospital
    • Hengshui Shi, Hebei, China, 053000
      • Hebei Medical University
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Luoyang, Henan, China, 471003
      • The First Affiliated Hospital of Henan University of Science &Technology
    • Zhengzhou Shi, Henan, China, 450014
      • The Second Affiliated Hospital of Zhengzhou University
  • Hunan
    • Yueyang, Hunan, China, 414000
      • The First People's Hospital of Yueyang
  • Inner Mongolia
    • Bao Tou, Inner Mongolia, China, 014040
      • Bao Tou Central Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213003
      • Changzhou No.2 People's Hospital
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210000
      • Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing University Medical School
    • Nanjing, Jiangsu, China, 211100
      • Nanjing Medical University - Nanjing Jiangning Hospital
    • Nanjing, Jiangsu, China, 210006
      • The First Hospital of Nanjing
    • Suzhou, Jiangsu, China, 215002
      • Suzhou Municipal Hospital
    • Suzhou, Jiangsu, China, 215066
      • The First Affiliated Hospital of Soochow University
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
    • Zhenjiang, Jiangsu, China, 212000
      • Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330009
      • The Third Hospital of Nanchang
  • Jilin
    • Changchun, Jilin, China, 130021
      • The First Hospital of Jilin University
  • Liaoning
    • Dalian, Liaoning, China, 116001
      • Dalian University - The Affiliated Zhongshan Hospital
    • Shenyang, Liaoning, China, 110004
      • Shengjing Hospital of China Medical University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710061
      • First Affiliated Hospital of Xi'an Jiaotong University
  • Shan XI
    • Tai Yuan, Shan XI, China, 030001
      • 1st Affiliated Hospital of Shanxi Medical University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
    • Qingdao, Shandong, China, 266042
      • Qingdao Central Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Shanghai 6th People's Hospital
  • Shanxi
    • XI 'an, Shanxi, China
      • The First Affiliated Hospital of Xi'an Medical University
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • West China Hospital Sichuan University
    • Chengdu, Sichuan, China, 611130
      • Chengdu Fifth People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Wanzhou
    • Wanzhou, Wanzhou, China, 404199
      • Chongqing Three Gorges Central Hospital
  • Yuzhong District
    • Chongqing, Yuzhong District, China, 400014
      • Chongqing General Hospital
  • Zhejiang
    • Huzhou, Zhejiang, China, 313000
      • Huzhou Central Hospital
    • Shaoxing, Zhejiang, China, 312000
      • Shaoxing People's Hospital
• India
  • Delhi, India, 110088
    • Fortis Hospital
  • Maharashtra
    • Mumbai, Maharashtra, India, 400012
      • King Edward Memorial Hospital and Research Center
    • Mumbai, Maharashtra, India, 400058
      • BSES Municipal General Hsptl
  • West Bengal
    • Kolkata, West Bengal, India, 700054
      • Apollo Gleneagles Hospitals Kolkata
• Korea, Republic of
  • Ansan-si, Korea, Republic of, 15355
    • Korea University Ansan Hospital
  • Seoul, Korea, Republic of, 03722
    • Severance Hospital
  • Seoul, Korea, Republic of, 05505
    • Asan Medical Center
  • Seoul, Korea, Republic of, 07441
    • Hallym University Kangnam Sacred Heart Hospital
  • Gangdong-gu
    • Seoul, Gangdong-gu, Korea, Republic of, 02447
      • Kyung Hee University Hospital
  • Geonggi-do
    • Seongnam, Geonggi-do, Korea, Republic of, 13620
      • Seoul National University Bundang Hospital
  • Gyeonggi-do
    • Bucheon,, Gyeonggi-do, Korea, Republic of, 14647
      • Bucheon St. Mary's Hospital
  • Gyeonggido
    • Guri-si, Gyeonggido, Korea, Republic of, 11923
      • Hanyang University Guri Hospital
  • Korea
    • Gangwon-do, Korea, Korea, Republic of, 220-701
      • Yonsei University Wonju Severance Christian Hospital
    • Ulsan, Korea, Korea, Republic of, 44033
      • Ulsan University Hospital
  • Seoul-teukbyeolsi
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 01757
      • Inje University Sanggye Paik Hospital
    • Seoul, Seoul-teukbyeolsi, Korea, Republic of, 02841
      • Korea University Anam Hospital
  • Taegu-Kwangyǒkshi
    • Daegu, Taegu-Kwangyǒkshi, Korea, Republic of, 41931
      • Keimyung University Dongsan Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 mg Tirzepatide; Participants received 5 milligrams (mg) tirzepatide administered subcutaneously (SC) once weekly (QW).	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 10 mg Tirzepatide; Participants received 10 mg tirzepatide administered SC QW.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 15 mg Tirzepatide; Participants received 15 mg tirzepatide administered SC QW.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Active Comparator: 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.	Drug: Insulin Glargine; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
Percentage of Participants Who Achieved Weight Loss ≥5%	Imputed data includes observed value and imputed value if endpoint measure is missing.	Week 40
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
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)

Collaborators and Investigators

• Sponsor: Eli Lilly and Company

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2019
• Primary Completion (Actual): November 1, 2021
• Study Completion (Actual): November 24, 2021

Study Registration Dates

• First Submitted: September 17, 2019
• First Submitted That Met QC Criteria: September 17, 2019
• First Posted (Actual): September 18, 2019

Study Record Updates

• Last Update Posted (Estimate): January 6, 2023
• Last Update Submitted That Met QC Criteria: December 12, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: T2DM
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Insulin Glargine; Tirzepatide
• Other Study ID Numbers: 17210; I8F-MC-GPHO (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: Data are available 6 months after the primary publication and approval of the indication studied in the US and 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; Statistical Analysis Plan (SAP); Clinical Study Report (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
• product manufactured in and exported from the U.S.: Yes