A Study of Orforglipron (LY3502970) in Participants With Type 2 Diabetes and Inadequate Glycemic Control With Insulin Glargine, With or Without Metformin and/or SGLT-2 Inhibitor (ACHIEVE-5)

Start 23 Feb 2024 · End 15 Sep 2025 · Status Ended · 1 EU/EEA countries · 10 sites · Protocol J2A-MC-GZGW

Overview

Sponsor-declared trial summary

Phase Therapeutic confirmatory (Phase III)

Status Ended

Participants planned 520

Countries 1

Sites 10

Type 2 Diabetes

The main purpose of this study is to determine the safety and efficacy of orforglipron. Participants will have Type 2 Diabetes (T2D) and have inadequate glycemic control with insulin glargine with or without metformin and/or SGLT-2 (sodium-glucose cotransporter-2) inhibitor.

Key facts

Sponsor: Eli Lilly & Co.
Participant type: Patients
Age range: 18-64 years, 65+ years
Gender: Male and Female
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]
Trial duration: 23 Feb 2024 → 15 Sep 2025
Decision date (initial): 2024-02-19
Transition trial: No
Low-intervention: No
Rare-disease indication: No
Vulnerable population: Yes

External identifiers

EU CT number: 2023-507280-18-00
WHO UTN: U1111-1294-2797

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Pharmacokinetic

Conditions and MedDRA coding

Type 2 Diabetes

Regulatory references

Scientific advice from competent authorities: European Medicines Agency
Plan to share IPD: Yes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

Have Type 2 Diabetes (T2D)
Be taking a consistent dose of diabetes drug by injection for at least 3 months.
May be taking up to 2 diabetes drugs by mouth for at least 3 months.
Have a high blood sugar.

Exclusion criteria 4

Have Type 1 diabetes.
Have history of an inflamed pancreas (pancreatitis).
Have history of an inflamed liver (hepatitis).
Have congestive heart failure.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

To demonstrate that orforglipron is superior to placebo in glycemic control.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 6

3-1S2S-1-5-S-22-DIMETHYLTETRAHYDRO-2H-PYRAN-4-YL-2-S-3-3-4-FLUORO-1-METHYL-1H-INDAZOL-5-YL-2-OXO-23-DIHYDRO-1H-IMIDAZOL-1-YL-2-4-FLUORO-35-DIMETHYLPHENYL-4-METHYL-4567-TETRAHYDRO-2H-PYRAZOLO43-CPYRIDINE-5-CARBONYL-1H-INDOL-1-YL-2-METHYLCYCLOPROPYL-5-OXO-124-OXADIAZOL-4-IDE Hemicalcium

PRD10193667 · Product

Active substance: 3-1S2S-1-5-S-22-DIMETHYLTETRAHYDRO-2H-PYRAN-4-YL-2-S-3-3-4-FLUORO-1-METHYL-1H-INDAZOL-5-YL-2-OXO-23-DIHYDRO-1H-IMIDAZOL-1-YL-2-4-FLUORO-35-DIMETHYLPHENYL-4-METHYL-4567-TETRAHYDRO-2H-PYRAZOLO43-CPYRIDINE-5-CARBONYL-1H-INDOL-1-YL-2-METHYLCYCLOPROPYL-5-OXO-124-OXADIAZOL-4-IDE Hemicalcium
Pharmaceutical form: CAPSULE
Route of administration: ORAL USE
Max daily dose: 0 Other
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: ELI LILLY AND COMPANY LIMITED
Paediatric formulation: No
Orphan designation: No

PRD10193651 · Product

Active substance: 3-1S2S-1-5-S-22-DIMETHYLTETRAHYDRO-2H-PYRAN-4-YL-2-S-3-3-4-FLUORO-1-METHYL-1H-INDAZOL-5-YL-2-OXO-23-DIHYDRO-1H-IMIDAZOL-1-YL-2-4-FLUORO-35-DIMETHYLPHENYL-4-METHYL-4567-TETRAHYDRO-2H-PYRAZOLO43-CPYRIDINE-5-CARBONYL-1H-INDOL-1-YL-2-METHYLCYCLOPROPYL-5-OXO-124-OXADIAZOL-4-IDE Hemicalcium
Pharmaceutical form: CAPSULE
Route of administration: ORAL USE
Max daily dose: 0 Other
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: ELI LILLY AND COMPANY LIMITED
Paediatric formulation: No
Orphan designation: No

PRD10193676 · Product

Active substance: 3-1S2S-1-5-S-22-DIMETHYLTETRAHYDRO-2H-PYRAN-4-YL-2-S-3-3-4-FLUORO-1-METHYL-1H-INDAZOL-5-YL-2-OXO-23-DIHYDRO-1H-IMIDAZOL-1-YL-2-4-FLUORO-35-DIMETHYLPHENYL-4-METHYL-4567-TETRAHYDRO-2H-PYRAZOLO43-CPYRIDINE-5-CARBONYL-1H-INDOL-1-YL-2-METHYLCYCLOPROPYL-5-OXO-124-OXADIAZOL-4-IDE Hemicalcium
Pharmaceutical form: CAPSULE
Route of administration: ORAL USE
Max daily dose: 0 Other
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: ELI LILLY AND COMPANY LIMITED
Paediatric formulation: No
Orphan designation: No

PRD10193655 · Product

Active substance: 3-1S2S-1-5-S-22-DIMETHYLTETRAHYDRO-2H-PYRAN-4-YL-2-S-3-3-4-FLUORO-1-METHYL-1H-INDAZOL-5-YL-2-OXO-23-DIHYDRO-1H-IMIDAZOL-1-YL-2-4-FLUORO-35-DIMETHYLPHENYL-4-METHYL-4567-TETRAHYDRO-2H-PYRAZOLO43-CPYRIDINE-5-CARBONYL-1H-INDOL-1-YL-2-METHYLCYCLOPROPYL-5-OXO-124-OXADIAZOL-4-IDE Hemicalcium
Pharmaceutical form: CAPSULE
Route of administration: ORAL USE
Max daily dose: 0 Other
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: ELI LILLY AND COMPANY LIMITED
Paediatric formulation: No
Orphan designation: No

PRD10193674 · Product

Active substance: 3-1S2S-1-5-S-22-DIMETHYLTETRAHYDRO-2H-PYRAN-4-YL-2-S-3-3-4-FLUORO-1-METHYL-1H-INDAZOL-5-YL-2-OXO-23-DIHYDRO-1H-IMIDAZOL-1-YL-2-4-FLUORO-35-DIMETHYLPHENYL-4-METHYL-4567-TETRAHYDRO-2H-PYRAZOLO43-CPYRIDINE-5-CARBONYL-1H-INDOL-1-YL-2-METHYLCYCLOPROPYL-5-OXO-124-OXADIAZOL-4-IDE Hemicalcium
Pharmaceutical form: CAPSULE
Route of administration: ORAL USE
Max daily dose: 0 Other
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: ELI LILLY AND COMPANY LIMITED
Paediatric formulation: No
Orphan designation: No

PRD10193663 · Product

Active substance: 3-1S2S-1-5-S-22-DIMETHYLTETRAHYDRO-2H-PYRAN-4-YL-2-S-3-3-4-FLUORO-1-METHYL-1H-INDAZOL-5-YL-2-OXO-23-DIHYDRO-1H-IMIDAZOL-1-YL-2-4-FLUORO-35-DIMETHYLPHENYL-4-METHYL-4567-TETRAHYDRO-2H-PYRAZOLO43-CPYRIDINE-5-CARBONYL-1H-INDOL-1-YL-2-METHYLCYCLOPROPYL-5-OXO-124-OXADIAZOL-4-IDE Hemicalcium
Pharmaceutical form: CAPSULE
Route of administration: ORAL USE
Max daily dose: 0 Other
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Not Authorised
MA holder: ELI LILLY AND COMPANY LIMITED
Paediatric formulation: No
Orphan designation: No

Placebo 1

Placebo to match LY3502970

N/A · Product

Other product name: N/A
Pharmaceutical form: N/A
ATC code: N/A — N/A
Marketing authorisation: N/A
MA holder: N/A
MA country: Iceland
Paediatric formulation: No

Auxiliary 4

Empagliflozin

SCP274026 · ATC

Active substance: Empagliflozin
Route of administration: ORAL USE
Max daily dose: 25 mg milligram(s)
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Authorised
ATC code: A10BK03 — EMPAGLIFLOZIN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Metformin

SCP135808 · ATC

Active substance: Metformin
Substance synonyms: DIMETHYLDIGUANIDE
Route of administration: ORAL USE
Max daily dose: 3000 mg milligram(s)
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Authorised
ATC code: A10BA02 — METFORMIN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

—

SCP183281 · ATC

Route of administration: SOLUTION FOR INJECTION
Max daily dose: 0 IU international unit(s)
Max total dose: 0 IU international unit(s)
Max treatment duration: 1 Week(s)
Authorisation status: Authorised
ATC code: A10AE04 — INSULIN GLARGINE
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Dapagliflozin

SCP153586 · ATC

Active substance: Dapagliflozin
Route of administration: ORAL USE
Max daily dose: 10 mg milligram(s)
Max total dose: 0 Other
Max treatment duration: 1 Week(s)
Authorisation status: Authorised
ATC code: A10BK01 — DAPAGLIFLOZIN
Marketing authorisation: -
Paediatric formulation: No
Orphan designation: No
Modified vs. Marketing Authorisation: No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Eli Lilly & Co.

Sponsor organisation: Eli Lilly & Co.
Address: 1 Lilly Corporate Center
City: Indianapolis
Postcode: 46285-0001
Country: United States

Scientific contact point

Organisation: Eli Lilly & Co.
Contact name: Lilly Clinical Trials information desk

Public contact point

Organisation: Eli Lilly & Co.
Contact name: Lilly Clinical Trials information desk

Third parties 8

Organisation	City, country	Duties
PPD Global Central Labs ORG-100046496	Zaventem, Belgium	Laboratory analysis
Greenphire LLC ORG-100041621	King Of Prussia, United States	Other
Iqvia Rds Inc. ORG-100043858	Durham, United States	On site monitoring
Eresearchtechnology Inc. ORG-100013039	Philadelphia, United States	Data management
IQVIA RDS (India) Private Limited ORG-100047036	Mumbai, India	Laboratory analysis
Q2 Solutions LLC ORG-100017000	Ithaca, United States	Laboratory analysis
Cleveland Clinic Foundation ORG-100028017	Cleveland, United States	Other
RWS Life Sciences Inc. ORG-100042348	East Hartford, United States	Data management

Locations

1 EU/EEA country · 10 investigational sites

By country

Country	MS status	Planned subjects	Sites
Romania	Ended	156	10
Rest of world China, United States, Brazil, Japan	—	364	—

Investigational sites

Romania

10 sites · Ended

Easydiet S.R.L.

Diabetes, Strada Alexandrescu Grigore Nr 80 Sector 1, 010627, Bucharest

Societatea Civila Medicala Dr. Paveliu

Diabetes, Strada Dr. Iatropol Panait 24, 050538, Bucharest

Milena Sante S.R.L.

Diabetes, Strada Balcescu Nicolae Nr 31, 800001, Galati

Dentosim-Queen S.R.L.

Diabetes, Strada Mihai Viteazul 27a, 540098, Targu Mures

Cabinet Medical Individual Diabet, Nutritie, Boli Metabolice Dr. Pop Lavinia

Diabetes, Strada George Cosbuc no. 25A / 2, Baia Mare,, Maramureș

Centrul Medical De Diagnostic Si Tratament Ambulator Neomed S.R.L.

Diabetes, Block 1 Staircase C Apartment 2 Room 2, Strada Crisului Nr 1, Brasov

Nutrilife S.R.L.

Diabetes, Strada Dobrogeanu-Gherea Constantin 10-12, 013764, Bucharest

Clinica Korall S.R.L.

Diabetes, P-Ta Eroii Revolutiei, Corp A Apartament M-2 Nr 22, Satu Mare

Diamed Obesity S.R.L.

Diabetes, Gheorghe Doja Nr 73, 800291, Galati

Diabdana S.R.L.

Diabetes, Calea Republicii Nr 77, 410147, Oradea

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country	Trial start	Trial end	Recruitment start	Recruitment end	Early termination
Romania	2024-02-23	2025-09-09	2024-02-26	2024-11-08

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 30 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Type	Title	Version
Recruitment arrangements (for publication)	K1_Recruitment Arrangements Statement	1.0
Recruitment arrangements (for publication)	K1_Recruitment arrangements_Annex 3_RO	1.0
Recruitment arrangements (for publication)	K2_Appreciation Items GZGW	2.0
Recruitment arrangements (for publication)	K2_List of participating sites_RO	1.0
Recruitment arrangements (for publication)	K2_Participant study guide_Redacted	1.0
Recruitment arrangements (for publication)	K2_Poster	1.0
Recruitment arrangements (for publication)	K2_Thank you card_Dropout	1.0
Recruitment arrangements (for publication)	K2_Thank you card_End of study	1.0
Recruitment arrangements (for publication)	K2_Thank you card_Participation	1.0
Recruitment arrangements (for publication)	K2_Thank you card_Screening	1.0
Recruitment arrangements (for publication)	K2_Visit card	1.0
Recruitment arrangements (for publication)	K3_Participant study guide_Redacted	1.0
Recruitment arrangements (for publication)	K3_Poster	1.0
Recruitment arrangements (for publication)	K3_Thank you card_Dropout	1.0
Recruitment arrangements (for publication)	K3_Thank you card_End of study	1.0
Recruitment arrangements (for publication)	K3_Thank you card_Participation	1.0
Recruitment arrangements (for publication)	K3_Thank you card_Screening	1.0
Recruitment arrangements (for publication)	K3_Visit card	1.0
Subject information and informed consent form (for publication)	L1_Addendum ICF_Prescreening	1.0
Subject information and informed consent form (for publication)	L1_ICF Reimbursement and or Reminder	1.0
Subject information and informed consent form (for publication)	L1_Main ICF_Redacted	2.0
Subject information and informed consent form (for publication)	L2_Other patient material_Patient card	1.0
Subject information and informed consent form (for publication)	L3_Ancillary Items List_Redacted	1.0
Subject information and informed consent form (for publication)	L3_Greenphire materials_ClinCard Cardholder FAQ	3.0
Subject information and informed consent form (for publication)	L3_Greenphire materials_ClinCard information	3.0
Subject information and informed consent form (for publication)	L3_Greenphire materials_ClinCard Msg Templates	6.0
Subject information and informed consent form (for publication)	L3_Greenphire materials_Details	1.0
Subject information and informed consent form (for publication)	L3_Greenphire materials_EU Generic ClinCard	3.0
Subject information and informed consent form (for publication)	L3_Greenphire materials_Fee_Schedule	1.0
Subject information and informed consent form (for publication)	L4_eCOA tablet_LTFQ	4.1

Application history

6 submissions — initial application plus substantial / non-substantial modifications

#	Type	Code	Submitted	Reference MS	Conclusion	Decision date
1	INITIAL	IN	2023-10-09	Romania	Acceptable 2024-02-12	2024-02-19
2	NON SUBSTANTIAL MODIFICATION	NSM-1	2024-03-14	Romania	Acceptable 2024-02-12	2024-03-14
3	SUBSTANTIAL MODIFICATION	SM-2	2024-03-19	Romania	Acceptable	2024-05-08
4	SUBSTANTIAL MODIFICATION	SM-3	2025-02-10	Romania	Acceptable	2025-04-15
5	NON SUBSTANTIAL MODIFICATION	NSM-2	2025-06-18	Romania	Acceptable	2025-06-18
6	NON SUBSTANTIAL MODIFICATION	NSM-3	2025-06-18	Romania	Acceptable	2025-06-18