A Study of Orforglipron (LY3502970) Compared With Semaglutide in Participants With Type 2 Diabetes Inadequately Controlled With Metformin

Phase 3

Completed

• Conditions: Type 2 Diabetes
• Interventions: Drug: Orforglipron; Drug: Semaglutide

• Registration Number: NCT06045221
• Lead Sponsor: Eli Lilly and Company

Brief Summary

The main purpose of this study is to assess efficacy and safety of orforglipron compared with oral semaglutide in participants with Type 2 diabetes and inadequate glycemic control with metformin.The study will last around 61 weeks.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2023-09-13
• Study First Submitted QC: 2023-09-13
• Study First Posted: 2023-09-21
• Study Start: 2023-09-22
• Primary Completion: 2025-08-22
• Study Completion: 2025-08-22
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-19
• Last Update Posted: 2025-09-22

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1698

Inclusion Criteria

• Have Type 2 Diabetes
• Have HbA1c ≥7.0% (53 mmol/mol) to ≤10.5% (91 mmol/mol), as determined by the central laboratory at screening.
• Have been on stable diabetes treatment with metformin ≥1500 milligram (mg)/day during the 90 days prior to screening and maintained through randomization.
• Are of stable body weight (±5%) for at least 90 days prior to screening and agree to not initiate an intensive diet or exercise program during the study with the intent of reducing body weight, other than the lifestyle and/or dietary measures for diabetes treatment

Exclusion Criteria

• Have Type 1 Diabetes
• Are currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema, for example, laser photocoagulation or intravitreal injections of anti-vascular endothelial growth factor inhibitors.
• Have a history of ketoacidosis or hyperosmolar state or coma within the last 6 months prior to screening, or between screening and randomization.
• Have a New York Heart Association functional classification IV congestive heart failure.
• Have an estimated glomerular filtration rate (eGFR) <45 milliliter/minute (mL/min)/1.73 square meter (m²) or lower than the country-specific threshold for discontinuing metformin therapy per local label as determined by the central laboratory at screening.
• Have a serum calcitonin level of ≥35 nanogram/Liter (ng/L), as determined by the central laboratory at screening.
• Have a history of an active or untreated malignancy or are in remission from a clinically significant malignancy for less than 5 years.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Orforglipron Dose 1	Orforglipron	Participants will receive orforglipron orally.
Orforglipron Dose 2	Orforglipron	Participants will receive orforglipron orally.
Semaglutide Dose 1	Semaglutide	Participants will receive semaglutide orally.
Semaglutide Dose 2	Semaglutide	Participants will receive semaglutide orally.

Primary Outcome Measures

Name	Time	Method
Change from Baseline in Hemoglobin A1c (HbA1c)	Baseline, Week 52

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants Who Achieved HbA1c ≤6.5% (48 mmol/mol)	Week 52
Percentage Change from Baseline in Body Weight	Baseline, Week 52
Change from Baseline in Body Weight	Baseline, Week 52
Percentage of Participants Who Achieved HbA1c <5.7% (39 mmol/mol)	Week 52
Change from Baseline in Fasting Serum Glucose	Baseline, Week 52
Change from Baseline in Daily Average 7-point Self-monitored Blood Glucose (SMBG)	Baseline, Week 52
Percentage of Participants Who Achieved Weight Loss of ≥5%	Week 52
Change from Baseline in HbA1c	Baseline, Week 52
Percentage of Participants Who Achieved HbA1c <7.0% 53 millimole/mole (mmol/mol)	Week 52
Change from Baseline in Diastolic Blood Pressure (DBP)	Baseline, Week 52
Percentage of Participants Who Achieved Weight Loss of ≥10%	Week 52
Percentage of Participants Who Achieved Weight Loss of ≥15%	Week 52
Change from Baseline in Systolic Blood Pressure (SBP)	Baseline, Week 52
Percentage Change from Baseline in Total Cholesterol	Baseline, Week 52
Percentage Change from Baseline in Very Low Density Lipoprotein (VLDL)-Cholesterol	Baseline, Week 52
Percentage Change from Baseline in High Density Lipoprotein (HDL)-Cholesterol	Baseline, Week 52
Percentage Change from Baseline in Low Density Lipoprotein (LDL)-Cholesterol	Baseline, Week 52
Percentage Change from Baseline in Triglycerides	Baseline, Week 52
Change from Baseline in Short Form 36 Version 2 (SF-36-v2) Acute Form Domain Summary Scores	Baseline, Week 52
Percentage Change from Baseline in Non-HDL-Cholesterol	Baseline, Week 52

Trial Locations

Locations (130)

Absolute Clinical Research; 🇺🇸 Phoenix, Arizona, United States

San Fernando Valley Health Institute; 🇺🇸 Canoga Park, California, United States

Neighborhood Healthcare Institute of Health; 🇺🇸 Escondido, California, United States

Velocity Clinical Research, Gardena; 🇺🇸 Gardena, California, United States

Biopharma Informatic, LLC; 🇺🇸 Los Angeles, California, United States

Velocity Clinical Research, Westlake; 🇺🇸 Los Angeles, California, United States

Infinity Clinical Research - Norco; 🇺🇸 Norco, California, United States

Valley Clinical Trials, Inc.; 🇺🇸 Northridge, California, United States

Norcal Endocrinology & Internal Medicine; 🇺🇸 San Ramon, California, United States

Encompass Clinical Research; 🇺🇸 Spring Valley, California, United States

Scroll for more (120 remaining)