A Study of Tirzepatide (LY3298176) in Chinese Participants With Type 2 Diabetes (SURPASS-CN-INS)

A Randomized, Phase 3, Double Blind Trial Comparing the Effect of the Addition of Tirzepatide Versus the Addition of Placebo to Titrated Basal Insulin on Glycemic Control in Chinese Participants With Type 2 Diabetes

The main purpose of this study is to compare the effect of the addition of tirzepatide or placebo to titrated basal insulin on glycemic control in Chinese participants with type 2 diabetes.

Study Overview

• Status: Completed
• Conditions: Glucose Metabolism Disorders; Diabetes Mellitus; Endocrine System Diseases; Metabolic Disease; Diabetes Type 2
• Intervention / Treatment: Drug: Tirzepatide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 257
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230011
      • The Second People's Hospital of Hefei
  • Beijing
    • Beijing, Beijing, China, 100005
      • Beijing Hospital
    • Beijing, Beijing, China, 101200
      • Beijing Pinggu District Hospital
  • Chongqing
    • Chongqing, Chongqing, China, 400014
      • Chongqing General Hospital
  • Guangdong
    • Huizhou, Guangdong, China, 516001
      • Huizhou Municipal Central Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The First Hospital of Harbin Medical University
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Hospital of Harbin Medical University
  • Henan
    • LuoyangShi, Henan, China, 471003
      • The First Affiliated Hospital of Henan University of Science &Technology
    • Zhengzhou, Henan, China, 450014
      • The Second Affiliated Hospital of Zhengzhou University
  • Hunan
    • Yueyang, Hunan, China, 414000
      • The First People's Hospital of Yueyang
  • Inner Mongolia
    • Baotou, Inner Mongolia, China, 014040
      • Baotou Central Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Changzhou No.2 People's Hospital
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China, 210009
      • Zhongda Hospital Southeast University
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
    • WuxiShi, Jiangsu, China, 214400
      • The Affiliated Jiangyin Hospital of Southeast University Medical College
    • Zhenjiang, Jiangsu, China, 212000
      • Affiliated Hospital of Jiangsu University
  • Jiangxi
    • Nanchang, Jiangxi, China, 330009
      • The Third Hospital of Nanchang
  • Shaanxi
    • Xi'an, Shaanxi, China, 710077
      • The First Affiliated Hospital of Xi'an Medical University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Sichuan
    • ChengDu, Sichuan, China, 610041
      • West China Hospital of Sichuan University
    • Chengdu, Sichuan, China, 611130
      • Chengdu Fifth People's Hospital
  • Tianjin
    • Tianjin, Tianjin, China, 300052
      • Tianjin Medical University General Hospital
  • Zhejiang
    • Huzhou, Zhejiang, China, 313000
      • Huzhou Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Have type 2 diabetes mellitus (T2DM)
• Have HbA1c ≥7.0% (53 mmol/mol) to ≤11% (97 mmol/mol)
• Have been treated with insulin glargine (U100) once daily alone, or in combination with metformin with or without SGLT-2i ≥90 days
• Have a body mass index (BMI) ≥23 kilograms per meter squared (kg/m²)

Exclusion Criteria:

• Have type 1 diabetes mellitus (T1DM)
• Have a history of chronic or acute pancreatitis
• Have proliferative diabetic retinopathy or diabetic macular edema or nonproliferative diabetic retinopathy that requires acute treatment
• Have a personal or family history of medullary thyroid carcinoma or personal history of multiple endocrine neoplasia syndrome type 2
• Have a history of severe hypoglycemia and/or hypoglycemia unawareness within the 6 months
• Have a history of diabetic ketoacidosis or hyperosmolar state/coma within the 6 months
• Have acute myocardial infarction, or cerebrovascular accident (stroke) or hospitalization due to congestive heart failure (CHF) in the past 2 months
• Have a serum calcitonin level of ≥35 ng/L, as determined by central laboratory
• Have acute or chronic hepatitis, signs, and symptoms of any other liver disease other than nonalcoholic fatty liver disease (NAFLD), or alanine aminotransferase (ALT) level >3.0 times the upper limit of normal (ULN), as determined by the central laboratory at study entry; participants with NAFLD are eligible for participation in this trial only if their ALT level is ≤3.0 times ULN.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 5 Milligram (mg) Tirzepatide; Participants received 5 mg of tirzepatide administered as subcutaneous (SC) injection via a single-dose injection pen (SDP) once weekly (QW) for 40 weeks. The starting dose of tirzepatide was 2.5 mg QW, which increased by 2.5 mg every 4 weeks until the maintenance dose of 5 mg was reached.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 10 mg Tirzepatide; Participants received 10 mg of tirzepatide administered as SC injection via a SDP QW for 40 weeks. The starting dose of tirzepatide was 2.5 mg QW, which increased by 2.5 mg every 4 weeks (2.5 mg to 5 mg to 7.5 mg to 10 mg) until the maintenance dose of 10 mg was reached.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Experimental: 15 mg Tirzepatide; Participants received 15 mg of tirzepatide administered as SC injection via a SDP QW for 40 weeks. The starting dose of tirzepatide was 2.5 mg QW, which increased by 2.5 mg every 4 weeks (2.5 mg to 5 mg to 7.5 mg to 10 mg to 12.5 mg to 15 mg) until the maintenance dose of 15 mg was reached.	Drug: Tirzepatide; Administered SC; Other Names: LY3298176
Placebo Comparator: Placebo; Participants received tirzepatide matched placebo administered as SC injection via a SDP QW for 40 weeks.	Drug: Placebo; Administered SC

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in HbA1c (Tirzepatide 10 or 15 Milligram [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 calculated using mixed model repeated measures (MMRM) for post-baseline measures: Variable = Baseline + SGLT2i Use (Yes/No) + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured	Baseline, Week 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean Change From Baseline in HbA1c (Tirzepatide 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 calculated using MMRM for post-baseline measures: Variable = Baseline + SGLT2i Use (Yes/No) + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured	Baseline, Week 40
Mean Change From Baseline in Body Weight	LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (<=8.0%, >8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured	Baseline, Week 40
Percentage of Participants With HbA1c <7.0% (53 Millimole/Mole [mmol/Mol]) and ≤6.5% (48 mmol/Mol)	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. The percentage of participants was calculated by dividing the number of participants reaching target HbA1c by the total number of participants analyzed, multiplied by 100. Percentage of Participants with HbA1c <7.0% (53 millimole/mole [mmol/mol]) and ≤6.5% (48 mmol/mol) is reported here.	Week 40
Mean Change From Baseline in Fasting Serum Glucose	LSMean was calculated using MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (<=8.0%, >8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured	Baseline, Week 40
Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 10 mg or 15 mg]	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Percentage of participants with HbA1c <5.7% (39 mmol/Mol) is reported here.	Week 40
Percentage of Participants With HbA1c <5.7% (39 mmol/Mol) [Tirzepatide 5 mg]	HbA1c is the glycosylated fraction of hemoglobin A. HbA1c is measured to identify average plasma glucose concentration over prolonged periods of time. Percentage of participants with HbA1c <5.7% (39 mmol/Mol) is reported here.	Week 40
Mean Change From Baseline in Daily Average 7-point Self-monitored Blood Glucose Profiles	The SMBG data were 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. The daily average was calculated as the average of the 7 blood glucose values collected on a particular day. LS Mean was calculated using MMRM for post-baseline measures: Variable = Baseline + Baseline HbA1c (<=8.0%, >8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Actual Value) = Unstructured. Variance-Covariance structure (Change from Baseline) = Unstructured.	Baseline, Week 40
Percentage of Participants Who Achieved Weight Loss of ≥5%	Percentage of Participants who Achieved Weight Loss ≥5% is reported here.	Week 40
Percentage of Participants Who Achieved Weight Loss of ≥10%	Percentage of Participants who Achieved Weight Loss ≥10% is reported here.	Week 40
Percentage of Participants Who Achieved Weight Loss of ≥15%	Percentage of Participants who Achieved Weight Loss ≥15% is reported here.	Week 40
Percent Change From Baseline in Daily Mean Insulin Glargine Dose	LS Mean was calculated using MMRM for post-baseline measures: log(Actual Measurement/Baseline) = log(Baseline) + Baseline HbA1c (<=8.0%, >8.0%) + SGLT2i Use (Yes/No) + Treatment + Time + Treatment*Time (Type III sum of squares). Variance-Covariance structure (Change from Baseline) = Unstructured.	Baseline, Week 40
Percentage of Participants With HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL])	Percentage of Participants with HbA1c <7.0%, Without Weight Gain (<0.1 Kilogram [kg]) and Without Hypoglycemia, (Blood Glucose <3.0 mmol/L <54 Milligram/Deciliter [mg/dL]) is reported here	Week 40
Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.0 mmol/L [54 mg/dL])	Percentage of Participants with HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood glucose <3.0 mmol/L [54 mg/dL]) is reported here.	Week 40
Percentage of Participants With HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia)	Percentage of Participants with HbA1c <7.0%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) is reported here.	Week 40
Percentage of Participants With HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood Glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia)	Percentage of Participants with HbA1c ≤6.5%, Without Weight Gain <0.1 kg and Without Hypoglycemia (Blood glucose <3.9 mmol/L [70 mg/dL] or Severe Hypoglycemia) is reported here.	Week 40

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

Study record dates

Study Major Dates

• Study Start (Actual): February 5, 2023
• Primary Completion (Actual): July 1, 2024
• Study Completion (Actual): July 1, 2024

Study Registration Dates

• First Submitted: January 11, 2023
• First Submitted That Met QC Criteria: January 11, 2023
• First Posted (Actual): January 20, 2023

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: July 21, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Diabetes Mellitus, Type 2; Diabetes Mellitus; Metabolic Diseases; Glucose Metabolism Disorders; Endocrine System Diseases; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Tirzepatide
• Other Study ID Numbers: 18552; I8F-MC-GPIM (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: ata are available 6 months after the primary publication and 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
• product manufactured in and exported from the U.S.: Yes