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> Record changed: 2026-10-13

# A Study of Daily Oral Orforglipron (LY3502970) Compared With Insulin Glargine in Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

NCT05803421

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

Phase

Phase 3

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

Recruitment status

Completed

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

Participants

2,749

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

Lead sponsor

Eli Lilly and Company

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

Start date

2023-04-03

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

Number of sites

358

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Title and summary

**Summary**

The main purpose of this study is to determine safety and efficacy of orforglipron compared with insulin glargine in participants with type 2 diabetes and obesity or overweight at increased cardiovascular risk. The study will last approximately 2 years may include up to 27 visits.

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Acronym**

ACHIEVE-4

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Short title**

A Study of Daily Oral Orforglipron (LY3502970) Compared With Insulin Glargine in Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Official title**

A Phase 3, Open-Label Study of Once Daily LY3502970 Compared With Insulin Glargine in Adult Participants With Type 2 Diabetes and Obesity or Overweight at Increased Cardiovascular Risk

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Status and phase

**Control arm**

Active comparator

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Registry reports results**

No

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Listing at source**

Listed

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Recruitment status**

Completed

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Phase**

Phase 3

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Study type**

Interventional

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Dates

**Completion date**

2026-03-16

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**First posted**

2023-04-07

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Registry last updated**

2026-04-17

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Primary completion date**

2026-03-16

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Start date**

2023-04-03

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Size and sites

**Actual participants**

2,749

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Participants**

2,749

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Participant count basis**

Actual

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Protocol amendments**

2

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Number of sites**

358

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Sponsor and oversight

**Data monitoring committee**

Yes

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Registry sponsor category**

Industry

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Lead sponsor**

Eli Lilly and Company

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Source registry**

ClinicalTrials.gov

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Identifiers

**Registry ID**

NCT05803421

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**ClinicalTrials.gov ID**

NCT05803421

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

**Registry record**

Open registry record

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Study design

**Allocation**

Randomised

**Model**

Parallel groups

**Purpose**

Treatment

**Masking**

No masking

Sources for study design

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Outcomes

### Primary outcomes

1. Time to First Occurrence of Any Major Adverse Cardiovascular Event (MACE-4) \[Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular (CV) Death\]  
Timeframe: Baseline to End of the Study (Approximate Maximum 104 Weeks)  
Time to First Occurrence of Any MACE-4 (Myocardial Infarction (MI), Stroke, Hospitalization for Unstable Angina, or Cardiovascular \\\[CV\\\] Death)

### Secondary outcomes

1. Time to First Occurrence of Any MACE-3 Event (MI, Stroke, or CV death)  
Timeframe: Baseline to End of the Study (Approximately 104 Weeks)  
Time to First Occurrence of Any MACE-3 Event (MI, Stroke, or CV death)
2. Change from Baseline in Hemoglobin A1c (HbA1c)  
Timeframe: Baseline, Week 52  
Change from Baseline in HbA1c
3. Change from Baseline in Fasting Serum Glucose  
Timeframe: Baseline, Week 52  
Change from Baseline in Fasting Serum Glucose
4. Change from Baseline in Daily Average 7-point Self-monitoring Blood Glucose (SMBG) Profile  
Timeframe: Baseline, Week 52  
Change from Baseline in Daily Average 7-point SMBG
5. Percentage of Participants with HbA1c Target Values Less Than (<)7.0% (53 mmol/mol)  
Timeframe: Week 52  
Percentage of Participants with HbA1c Target Values \\<7.0% (53 mmol/mol)
6. Change from Baseline in Body Weight  
Timeframe: Baseline, Week 52  
Change from Baseline in Body Weight
7. Percent Change from Baseline Body Weight  
Timeframe: Week 52  
Percent Change from Baseline Body Weight
8. Change from Baseline in Short Form 36 Version 2 (SF-36v2) Acute Form Domain Score  
Timeframe: Baseline, Week 52  
The SF-36v2 acute form is a 36-item generic, participant completed measure designed to assess 8 domains: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health. Scores of each domain are measured by T-scores, with a mean of 50 and standard deviation of 10; higher scores indicate better levels of function and/or better health.
9. Pharmacokinetics (PK): Plasma Serum Concentrations of Orforglipron  
Timeframe: Baseline through Week 52  
PK will be estimated based on the population PK model.

Sources for outcomes

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Eligibility

**Sex**

All

**Age groups**

Adults, Older adults

**Minimum age**

18 Years

**Healthy volunteers**

No

### Inclusion criteria

- Have been diagnosed with type 2 diabetes mellitus (T2DM)
- Are at least 18 years of age or legal age of consent in the jurisdiction in which the study is taking place, whichever is older.
- Have HbA1c at screening

  - ≥7.0% and ≤10.5% if background diabetes medication does not include a sulfonylurea, or
  - ≥7.5% and ≤10.5% if background diabetes medication includes a sulfonylurea.
- Are on stable treatment of at least 1 and no more than 3 oral antihyperglycemic drugs for at least 90 days before screening. Antihyperglycemic drugs may include metformin, SGLT-2 inhibitors, and/or sulfonylureas
- Have increased risk for cardiovascular (CV) events due to:

  - Coronary heart disease
  - Peripheral arterial disease, presumed to be of atherosclerotic origin
  - Cerebrovascular disease, presumed to be of atherosclerotic origin
  - Chronic kidney disease (CKD)
  - Congestive heart failure (CHF) New York Heart Association (NYHA) functional classification II to III
- Are of stable weight (± 5%) for at least 90 days prior to screening
- Have a BMI ≥25 kilograms per meter squared (kg/m2) at screening

### Exclusion criteria

- Have type 1 diabetes mellitus
- Have had chronic or acute pancreatitis any time prior to screening
- Currently receiving or planning to receive treatment for diabetic retinopathy and/or macular edema (e.g. laster photocoagulation or intravitreal injections of anty-VEGF inhibitors
- Have a known clinically significant gastric emptying abnormality
- Have acute or chronic hepatitis, signs and symptoms of any other liver disease, or blood alanine transaminase (ALT) or aspartate aminotransferase (AST) enzyme level ≥5.0 times the upper limit of normal (ULN) for the reference range, as determined by the central laboratory
- Have had any of the following within 60 days prior to screening: acute myocardial infarction, cerebrovascular accident (stroke), or hospitalization for congestive heart failure
- Have an eGFR <15 mL/min/1.73 m2 as determined at screening
- Have a family (first-degree relative) or personal history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- Have been taking any other diabetes medicines other than metformin, SGLT-2 inhibitors, and/or sulfonylureas during the last 90 days
- Have used any weight loss drugs, including herbal or nutritional supplements, within 90 days of screening

Sources for eligibility

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Sites

- Alliance for Multispecialty Research, LLCDaphne, United States
- Alliance for Multispecialty Research, LLCMobile, United States
- Cahaba Research - PelhamPelham, United States
- Syed Research Consultants LlcSheffield, United States
- The Institute for Liver HealthChandler, United States
- Aventiv ResearchMesa, United States
- Arizona Liver Health - PeoriaPeoria, United States
- Elite Clinical Studies, LLCPhoenix, United States
- Absolute Clinical ResearchPhoenix, United States
- Clinical Research Institute of Arizona (CRI) - Sun City WestSun City West, United States
- Alliance for Multispecialty Research, LLCTempe, United States
- Orange Grove Family PracticeTucson, United States
- KLR Business Group, Inc. dba Arkansas Clinical ResearchLittle Rock, United States
- Hope Clinical Research, Inc.Canoga Park, United States
- Valley Clinical Trials, Inc.Covina, United States
- Neighborhood Healthcare Institute of HealthEscondido, United States
- Valley ResearchFresno, United States
- Orange County Research CenterLake Forest, United States
- Ark Clinical ResearchLong Beach, United States
- Pacific Clinical StudiesLos Alamitos, United States
- Velocity Clinical Research, Los AngelesLos Angeles, United States
- Infinity Clinical Research - NorcoNorco, United States
- Velocity Clinical Research, North HollywoodNorth Hollywood, United States
- Valley Clinical Trials, Inc.Northridge, United States
- Rancho Cucamonga Clinical ResearchRancho Cucamonga, United States

And 333 more, listed on the interactive page.

Sources for sites

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## References

- Related resource (trials.lilly.com)  
Source: [trials.lilly.com](https://trials.lilly.com/en-US/trial/397395)

### Other registry identifiers (3)

- 2022-502833-25-00
- J2A-MC-GZGS
- U1111-1285-6821

Sources for references

Source: [clinicaltrials.gov](https://clinicaltrials.gov/study/NCT05803421)

## Related records

### Drugs (2)

- [Insulin glargine](https://trialight.com/data/asset/insulin-glargine-8aa23d8d-fb05-42b5-b490-2e4b67136155.md)
- [Orforglipron](https://trialight.com/data/asset/orforglipron-1138c12b-f1c7-45bb-b9ec-2b693f019a62.md)

### Lead sponsors (1)

- [Eli Lilly and Company](https://trialight.com/data/company/eli-lilly-and-company-9da7efcc-bafe-4b95-b30b-e87a97770db7.md)

### Conditions (4)

- [Chronic kidney disease](https://trialight.com/data/condition/chronic-kidney-disease-dc1fecbb-338b-5bbc-8d68-08e49db49918.md)
- [Kidney failure](https://trialight.com/data/condition/kidney-failure-f26737b4-3a55-50be-b6c3-b76514cb5067.md)
- [Obesity disorder](https://trialight.com/data/condition/obesity-disorder-f3b57dc0-68ac-555c-8f13-0d81e595d9cb.md)
- [Type 2 diabetes mellitus](https://trialight.com/data/condition/type-2-diabetes-mellitus-98e14a90-bb06-5174-90c7-901a0a259fb9.md) Primary condition

### Targets (1)

- [INSR](https://trialight.com/data/target/insr-76e92e6a-1d95-5282-9c03-f55293267050.md)

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