A Study of Orforglipron in Adult Participants With Obesity or Overweight and Type 2 Diabetes (ATTAIN-2)

A Phase 3, Randomized, Double-Blind Study to Investigate the Efficacy and Safety of Once-Daily Oral LY3502970 Compared With Placebo in Adult Participants With Obesity or Overweight and Type 2 Diabetes (ATTAIN-2)

This study will investigate the safety and efficacy of once daily oral treatment with orforglipron compared with placebo on body weight in adult participants with obesity or overweight and type 2 diabetes. The study will last about 77 weeks and may include up to 22 visits.

Study Overview

• Status: Completed
• Conditions: Obesity; Overweight; Type 2 Diabetes
• Intervention / Treatment: Drug: Placebo; Drug: Orforglipron

• Study Type: Interventional
• Enrollment (Actual): 1613
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, 1012
    • CONEXA Investigacion Clinica S.A.
  • Córdoba, Argentina, 5000
    • Centro Diabetológico Dr. Waitman
  • Córdoba, Argentina, X50004FHP
    • Clínica Universitaria Reina Fabiola
  • Santa Fe, Argentina, 3000
    • Centro de Diagnóstico y Rehabilitación (CEDIR)
  • Buenos Aires F.D.
    • Buenos Aires, Buenos Aires F.D., Argentina, C1128AAF
      • Mautalen Salud e investigación
  • Ciudad Aut
    • C.a.b.a., Ciudad Aut, Argentina, C1205AAO
      • CEMEDIAB
  • Ciudad Autónoma de Buenos Aire
    • CABA, Ciudad Autónoma de Buenos Aire, Argentina, 1204
      • Instituto Centenario
  • Santa Fe Province
    • Rosario, Santa Fe Province, Argentina, 2000
      • Instituto de Investigaciones Clinicas Rosario
    • Rosario, Santa Fe Province, Argentina, 2000
      • Instituto Médico Fundación Grupo Colaborativo Rosario Investigación y Prevención Medica
    • Venado Tuerto, Santa Fe Province, Argentina, 2600
      • Sanatorio San Martin
  • Tucumán Province
    • SAN M. de Tucuman, Tucumán Province, Argentina, T4000AXL
      • Centro de Investigaciones Médicas Tucuman
• Australia
  • New South Wales
    • Botany, New South Wales, Australia, 2019
      • Emeritus Research
    • Merewether, New South Wales, Australia, 2291
      • The AIM Centre / Hunter Diabetes Centre
  • Queensland
    • Brisbane, Queensland, Australia, 4029
      • Royal Brisbane and Women's Hospital
    • Brisbane, Queensland, Australia, 4064
      • Core Research Group
    • Meadowbrook, Queensland, Australia, 4131
      • Logan Hospital
  • South Australia
    • Oaklands Park, South Australia, Australia, 5046
      • Southern Adelaide Diabetes & Endocrine services
  • Victoria
    • Box Hill, Victoria, Australia, 3128
      • Box Hill Hospital
    • Camberwell, Victoria, Australia, 3124
      • Emeritus Research
    • Heidelberg West, Victoria, Australia, 3081
      • Austin Health - Repatriation Hospital
    • Melbourne, Victoria, Australia, 3004
      • Baker IDI Heart and Diabetes Institute - Melbourne
  • Western Australia
    • Joondalup, Western Australia, Australia, 6027
      • Advara HeartCare Joondalup
• Brazil
  • São Paulo, Brazil, 04266-010
    • CEPIC - Centro Paulista de Investigação Clínica
  • Federal District
    • Brasília, Federal District, Brazil, 71625-175
      • Centro de Pesquisa Clinica do Brasil
  • Goiás
    • Goiânia, Goiás, Brazil, 74230-035
      • Cendi - Endocrinologia e Diabetes
  • Rio Grande do Sul
    • Passo Fundo, Rio Grande do Sul, Brazil, 99010-120
      • Instituto Méderi de Pesquisa e Saúde
  • Rio de Janeiro
    • Volta Redonda, Rio de Janeiro, Brazil, 27253-003
      • Instituto Lóbus
  • São Paulo
    • Campinas, São Paulo, Brazil, 13060-080
      • Instituto de Pesquisa Clínica de Campinas
    • Marília, São Paulo, Brazil, 17504-072
      • Centro de Pesquisa Clínica de Marília - CPCLIM
    • Santo André, São Paulo, Brazil, 09080-110
      • Pesquisare Saúde
• China
  • Anhui
    • Hefei, Anhui, China, 230011
      • The Second People's Hospital of Hefei
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100853
      • Chinese PLA General Hospital
  • Chongqing Municipality
    • Chongqing, Chongqing Municipality, China, 400014
      • Chongqing General Hospital
  • Guangdong
    • Shenzhen, Guangdong, China, 518020
      • Shenzhen People's Hospital
  • Heilongjiang
    • Harbin, Heilongjiang, China, 150001
      • The Fourth Affiliated Hospital of Harbin Medical University
  • Henan
    • Luoyang Shi, Henan, China, 471003
      • The First Affiliated Hospital of Henan University of Science &Technology
    • Zhengzhou, Henan, China, 450014
      • The Second Affiliated Hospital of Zhengzhou University
  • Jiangsu
    • Nanjing, Jiangsu, China, 210006
      • Nanjing First Hospital
    • Nanjing, Jiangsu, China, 210011
      • The Second Affiliated Hospital of Nanjing Medical University
    • Nanjing, Jiangsu, China, 210008
      • Jiangsu Province Official Hospital
    • Nantong, Jiangsu, China, 226001
      • Nantong First People's Hospital
    • Wuxi, Jiangsu, China, 214023
      • Wuxi People's Hospital
  • Jiangxi
    • Nanchang, Jiangxi, China, 330006
      • Jiangxi Provincial People's Hospital
  • Liaoning
    • Dalian, Liaoning, China, 116033
      • Dalian Municipal Central Hospital Affiliated of Dalian Medical University
  • Shandong
    • Jinan, Shandong, China, 250013
      • Jinan Central Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300052
      • Tianjin Medical University General Hospital
    • Tianjin, Tianjin Municipality, China
      • Tianjin Medical University Zhu Xianyi Memorial Hospital
  • Yunnan
    • Kunming, Yunnan, China, 650034
      • The First People's Hospital of Yunnan Province
• Czechia
  • Hradec Králové, Czechia, 500 12
    • Endokrinologie MUDr. Rehorkova s.r.o.
  • Pilsen, Czechia, 326 00
    • MUDr. Jitka Zemanová - diabetologie a interna s.r.o.
  • Český Krumlov, Czechia, 381 01
    • Nemocnice Cesky Krumlov
  • Central Bohemia
    • Příbram, Central Bohemia, Czechia, 26201
      • Milan Kvapil s.r.o., Diabetologicka ambulance Pribram
  • Moravskosl
    • Krnov, Moravskosl, Czechia, 79401
      • MUDr. Tomas Edelsberger
  • Pardubice
    • Pardubice V, Pardubice, Czechia, 530 02
      • Diahelp s.r.o
  • Plzeň-město
    • Pilsen, Plzeň-město, Czechia, 301 00
      • Dialine - Interni a diabetologicka ambulance
  • Praha 1
    • Prague, Praha 1, Czechia, 11000
      • Diabet2 s.r.o., diabetologicka a interni ambulance
  • Praha 4
    • Prague, Praha 4, Czechia, 14900
      • Milan Kvapil s.r.o., Diabetologicka ambulance
  • Praha 8
    • Prague, Praha 8, Czechia, 18100
      • ResTrial s.r.o.
  • Praha-západ
    • Jílové u Prahy, Praha-západ, Czechia, 252 42
      • MUDr. Sabina Palova
  • South Bohemian Region
    • České Budějovice, South Bohemian Region, Czechia, 37011
      • MUDr. Alena Váchová
• Germany
  • Gelnhausen, Germany, 63571
    • Diabetes Zentrum Dr. Tews
  • Hamburg, Germany, 21109
    • Diabetes Zentrum Wilhelmsburg
  • Bavaria
    • München, Bavaria, Germany, 80809
      • CDG Studienambulanz Hartard
    • Wallerfing, Bavaria, Germany, 94574
      • Gemeinschaftspraxis Dr. med. Josef und Wilma Großkopf
  • Hesse
    • Pohlheim, Hesse, Germany, 35415
      • Ceda-Research
  • Nordrhein-
    • Münster, Nordrhein-, Germany, 48145
      • Institut für Diabetesforschung GmbH Münster
  • North Rhine-Westphalia
    • Cologne, North Rhine-Westphalia, Germany, 50937
      • Universitaetsklinikum Koeln
    • Essen, North Rhine-Westphalia, Germany, 45355
      • Medizentrum Essen Borbeck
    • Essen, North Rhine-Westphalia, Germany, 45136
      • InnoDiab Forschung GmbH
  • Saxony
    • Leipzig, Saxony, Germany, 04107
      • AmBeNet GmbH
    • Pirna, Saxony, Germany, 01796
      • Arztpraxis Christine Kosch Pirna
  • Saxony-Anhalt
    • Hohenmölsen, Saxony-Anhalt, Germany, 06679
      • Hausarzt- und Diabetologische Schwerpunktpraxis Hohenmölsen - Weiβenfels
    • Magdeburg, Saxony-Anhalt, Germany, 39120
      • SMO.MD GmbH
  • Schleswig-Holstein
    • Lübeck, Schleswig-Holstein, Germany, 23562
      • Universität zu Lübeck - Institut für Endokrinologie und Diabetes
    • Oldenburg in Holstein, Schleswig-Holstein, Germany, 23758
      • Red-Institut GmbH
• Greece
  • Thessaloniki, Greece, 564 29
    • 424 Military General Training Hospital
  • Attikí
    • Athens, Attikí, Greece, 151 25
      • Athens Medical Center
  • Kentrikí Makedonía
    • Thessaloniki, Kentrikí Makedonía, Greece, 54642
      • Ippokrateio General Hospital of Thessaloniki
  • Thessaloníki
    • Thessaloniki, Thessaloníki, Greece, 570 01
      • Thermi Clinic
    • Thessaloniki, Thessaloníki, Greece, 546 45
      • Euromedica General Clinic of Thessaloniki
    • Thessaloniki, Thessaloníki, Greece, 564 29
      • Papageorgiou General Hospital of Thessaloniki
  • Thessalía
    • Larissa, Thessalía, Greece, 41110
      • University General Hospital of Larissa
• India
  • Karnataka
    • Bangalore, Karnataka, India, 560092
      • Medstar Speciality Hospital
    • Hubli, Karnataka, India, 580021
      • Karnataka Institute of Medical Sciences
  • Madhya Pradesh
    • Indore, Madhya Pradesh, India, 452010
      • TOTALL Diabetes Hormone Institute
  • Maharashtra
    • Mumbai, Maharashtra, India, 400008
      • Topiwala National Medical College & B. Y. L. Nair Charitable Hospital
    • Mumbai, Maharashtra, India, 400058
      • BSES MG Hospital
    • Nagpur, Maharashtra, India, 441108
      • All India Institute of Medical Sciences (AIIMS) - Nagpur
    • Pune, Maharashtra, India, 411004
      • Sahyadri Super Speciality Hospital
  • Tamil Nadu
    • Madurai, Tamil Nadu, India, 625020
      • Arthur Asirvatham Hospital
  • Telangana
    • Hyderabad, Telangana, India, 500082
      • Kumudini Devi Diabetes Research Center
• Puerto Rico
  • PR
    • Bayamón, PR, Puerto Rico, 00959
      • Advanced Clinical Research, LLC
    • Guaynabo, PR, Puerto Rico, 00968
      • Isis Clinical Research Center
• South Korea
  • Kang-won-do
    • Wŏnju, Kang-won-do, South Korea, 26426
      • Yonsei University-Wonju Severance Christian Hospital
  • Kyǒnggi-do
    • Seongnam, Kyǒnggi-do, South Korea, 13620
      • Seoul National University Bundang Hospital
  • Kyǒngsangbuk-do
    • Gyeongsan-si, Kyǒngsangbuk-do, South Korea, 42415
      • Yeungnam Univeristy Medical Center
  • Seoul-teukbyeolsi [Seoul]
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 02841
      • Korea University Anam Hospital
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 06591
      • The Catholic Univ. of Korea Seoul St. Mary's Hospital
    • Seoul, Seoul-teukbyeolsi [Seoul], South Korea, 134-090
      • Kyung Hee University Hospital at Gangdong
• United States
  • Alabama
    • Pelham, Alabama, United States, 35124
      • Cahaba Research - Pelham
  • Arizona
    • Tucson, Arizona, United States, 85741
      • Novak Clinical Research - Tucson - North La Cholla Boulevard
    • Yuma, Arizona, United States, 85364
      • Yuma Clinical Trials
  • California
    • Escondido, California, United States, 92025
      • AMCR Institute
    • Huntington Park, California, United States, 90255
      • Velocity Clinical Research, Huntington Park
    • Los Angeles, California, United States, 90057
      • Velocity Clinical Research, Westlake
    • Montclair, California, United States, 91763
      • Catalina Research Institute, LLC
    • Tustin, California, United States, 92780
      • University Clinical Investigators, Inc.
  • Florida
    • Hollywood, Florida, United States, 33024
      • Encore Medical Research
    • Jacksonville, Florida, United States, 32216
      • East Coast Institute for Research, LLC
    • Margate, Florida, United States, 33063
      • South Florida Clinical Research Institute
    • New Port Richey, Florida, United States, 34652
      • Suncoast Clinical Research, Inc.
  • Georgia
    • Lawrenceville, Georgia, United States, 30046
      • Balanced Life Health Care Solutions/SKYCRNG
    • Roswell, Georgia, United States, 30076
      • Endocrine Research Solutions, Inc.
    • Woodstock, Georgia, United States, 30189
      • North Georgia Clinical Research
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Pacific Diabetes & Endocrine Center
  • Idaho
    • Meridian, Idaho, United States, 83646
      • Solaris Clinical Research
  • Iowa
    • West Des Moines, Iowa, United States, 50265
      • Iowa Diabetes and Endocrinology Research Center
  • Maryland
    • Baltimore, Maryland, United States, 21239
      • MedStar Good Samaritan Hospital
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division
  • Missouri
    • City of Saint Peters, Missouri, United States, 63303
      • StudyMetrix Research
  • Nevada
    • Las Vegas, Nevada, United States, 89128
      • Las Vegas Medical Research
  • New Mexico
    • Albuquerque, New Mexico, United States, 87109
      • IMA Clinical Research
  • New York
    • Albany, New York, United States, 12203
      • Albany Medical College, Division of Community Endocrinology
    • Albany, New York, United States, 12208
      • Albany Stratton VA Medical Center
    • Long Island City, New York, United States, 11106
      • NYC Research INC
  • North Carolina
    • Raleigh, North Carolina, United States, 27609
      • Accellacare - Raleigh
  • Oregon
    • Portland, Oregon, United States, 97210
      • Summit Headlands
  • Tennessee
    • Knoxville, Tennessee, United States, 37909
      • Alliance for Multispecialty Research, LLC
  • Texas
    • Dallas, Texas, United States, 75230
      • Velocity Clinical Research, Dallas
    • DeSoto, Texas, United States, 75115
      • Epic Medical Research - DeSoto
    • Denison, Texas, United States, 75020
      • Soma Clinical Trials
    • Houston, Texas, United States, 77043
      • Biopharma Informatic, LLC
    • San Antonio, Texas, United States, 78230
      • VIP Trials
    • San Antonio, Texas, United States, 78229
      • Diabetes and Glandular Disease Center
  • Virginia
    • Charlottesville, Virginia, United States, 22911
      • Charlottesville Medical Research
  • Washington
    • Tacoma, Washington, United States, 98405
      • Universal Research Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Have a body mass index (BMI) ≥27.0 kilogram/square meter (kg/m²).
• Have a history of at least 1 self-reported unsuccessful dietary effort to lose body weight.

• Have a diagnosis of Type 2 Diabetes (T2D), with HbA1c ≥7% (≥53 mmol/mol) to ≤10% (86 mmol/mol) and are on stable treatment for T2D for at least 90 days prior to screening, consisting of:

  • either diet/exercise alone or
  • up to 3 oral antihyperglycemic medications (excluding dipeptidyl peptidase IV inhibitors (DPP-4i) or glucagon-like peptide-1 (GLP-1) receptor agonists (RA).

Exclusion Criteria:

• Have Type 1 Diabetes (T1D), history of ketoacidosis or hyperosmolar state/coma, or any other types of diabetes except T2D.
• Have a self-reported change in body weight >5 kg (11 pounds) within 90 days prior to screening.
• 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 family (first-degree relative) or personal history of medullary thyroid cancer (MTC) or multiple endocrine neoplasia 2 (MEN2) syndrome.
• Have had a history of chronic or acute pancreatitis.

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
Placebo Comparator: Placebo; Participants received matching placebo capsule orally once daily (QD). Treatment was initiated with placebo corresponding to 1 milligram (mg) equivalent to Orforglipron, with dose escalation every 4 weeks to maintain blinding, and was continued through Week 72, unless dose modification was required.	Drug: Placebo; Administered orally
Experimental: 6 mg Orforglipron QD; Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 6 mg, which was maintained through Week 72, unless dose modification was required.	Drug: Orforglipron; Administered orally; Other Names: LY3502970
Experimental: 12 mg Orforglipron QD; Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 12 mg, which was maintained through Week 72, unless dose modification was required.	Drug: Orforglipron; Administered orally; Other Names: LY3502970
Experimental: 36 mg Orforglipron QD; Participants received oral orforglipron capsule once daily. Treatment was initiated at 1 mg once daily, with dose escalation every 4 weeks to a target dose of 36 mg, which was maintained through Week 72, unless dose modification was required.	Drug: Orforglipron; Administered orally; Other Names: LY3502970

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change From Baseline in Body Weight	Values represented under Least Squares (LS) Mean are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral antihyperglycemic medications (AHMs) classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 72

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Who Achieved With Greater Than or Equal to (≥) 5% Body Weight Reduction From Baseline	Percentage of participants with ≥5% body weight reduction was analysed by Logistic regression with the following variables: region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality).	Baseline to Week 72
Percentage of Participants Who Achieved ≥10% Body Weight Reduction From Baseline	Percentage of participants with ≥10% body weight reduction was analysed by Logistic regression with the following variables: region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality).	Baseline to Week 72
Percentage of Participants Who Achieved ≥15% Body Weight Reduction From Baseline	Percentage of participants with ≥15% body weight reduction was analysed by Logistic regression with the following variables: region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality).	Baseline to Week 72
Change From Baseline in Waist Circumference	Values represented under Least Squares (LS) Mean are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 72
Change From Baseline in Hemoglobin A1c (HbA1c) %	Hemoglobin A1c (HbA1c) is the glycosylated fraction of hemoglobin A, measured to reflect average plasma glucose concentration over prolonged periods of time.; Values represented under Least Squares (LS) Mean are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 72
Change From Baseline in Fasting Serum Glucose (FSG)	Values represented under Least Squares (LS) Mean are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 72
Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<6.5%)	Percentage of participants who achieved hemoglobin A1c (HbA1c<6.5%) was analysed by Logistic regression with the following variables: region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality).	Baseline to Week 72
Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<7.0%)	Percentage of participants who achieved hemoglobin A1c (HbA1c<7%) was analysed by Logistic regression with the following variables: region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality).	Baseline to Week 72
Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)	Values represented under Least Squares (LS) Mean are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 72
Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)	Values represented under Least Squares (LS) Mean are model-based estimates (MBE) of the unconditional average treatment effect. MBE was calculated using a mixed-model repeated measures (MMRM) for post-baseline measures with region + Baseline*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). Variance-covariance structure for change from baseline was unstructured.	Baseline, Week 72
Percent Change From Baseline in Fasting Insulin	Fasting Insulin is a test used to measure the amount of insulin in the body.; Values represented under "Geometric Least Squares Mean" are model-based estimates (MBE) of the unconditional average treatment effect. For post-baseline measures, MBE was calculated using a mixed-model repeated measures (MMRM) on log-transformed values, defined as log (Actual Measurement/Baseline) + Region + log (Baseline)*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). The variance-covariance structure was unstructured.	Baseline, Week 72
Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)	Values represented under "Geometric Least Squares Mean" are model-based estimates (MBE) of the unconditional average treatment effect. For post-baseline measures, MBE was calculated using a mixed-model repeated measures (MMRM) on log-transformed values, defined as log (Actual Measurement/Baseline) + Region + log (Baseline)*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). The variance-covariance structure was unstructured.	Baseline, Week 72
Percent Change From Baseline in Triglycerides (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)	Values represented under "Geometric Least Square Mean" are model-based estimates (MBE) of the unconditional average treatment effect. For post-baseline measures, MBE was calculated using a mixed-model repeated measures (MMRM) on log-transformed values, defined on log-transformed values, defined as log (Actual Measurement/Baseline) + Region + log (Baseline)*Time*Treatment + Strata*Time*Treatment in the model. Strata were defined by joint levels of sex (female, male) and background oral AHMs classified according to their potential effect on body weight (promoting weight gain, weight reduction, or weight neutrality). The variance-covariance structure was unstructured.	Baseline, Week 72
Change From Baseline in Short Form-36 Health Survey Version 2 (SF-36v2) Acute Form (Physical-Component and Mental-Component) Scores (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)	The SF-36v2 acute form, (1-week recall version) assesses participants' health-related quality of life on 8 domains: Physical Functioning, Role-Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health. The physical functioning domain assesses limitations due to health "now," whereas the remaining domains assess functioning "in the past week." Each domain is scored individually, and information from these 8 domains is aggregated into 2 health component summary scores, the Physical Component Summary and Mental Component Summary. Items are answered on Likert scales of varying lengths (3-point, 5-point, or 6-point scales). Scoring of each domain and both summary scores are norm based and presented in the form of T-scores, with a mean of 50 and a standard deviation of 10. Higher scores indicate better levels of function and/or better health. Range cannot be specified in norm-based scores.	Baseline, Week 72

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

Publications and helpful links

General Publications

• Horn DB, Shukla AP, Huang H, Twum E, Allen SE, Kis SG. Orforglipron for obesity treatment in older patients >/=65 years with or without type 2 diabetes: A post hoc subgroup analysis of the ATTAIN-1 and ATTAIN-2 trials. Obes Pillars. 2026 Jul 14;19:100301. doi: 10.1016/j.obpill.2026.100301. eCollection 2026 Sep.
• Horn DB, Ryan DH, Kis SG, Alves B, Mu Y, Kim SG, Aberle J, Bain SC, Allen S, Sarker E, Wu Q, Stefanski A, Jouravskaya I; ATTAIN-2 Trial Investigators. Orforglipron, an oral small-molecule GLP-1 receptor agonist, for the treatment of obesity in people with type 2 diabetes (ATTAIN-2): a phase 3, double-blind, randomised, multicentre, placebo-controlled trial. Lancet. 2026 Dec 20;406(10522):2927-2944. doi: 10.1016/S0140-6736(25)02165-8. Epub 2025 Nov 20.

Helpful Links

• A Study of Orforglipron in Adult Participants With Obesity or Overweight and Type 2 Diabetes (ATTAIN-2)

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2023
• Primary Completion (Actual): August 8, 2025
• Study Completion (Actual): August 8, 2025

Study Registration Dates

• First Submitted: May 15, 2023
• First Submitted That Met QC Criteria: May 15, 2023
• First Posted (Actual): May 24, 2023

Study Record Updates

• Last Update Posted (Actual): September 4, 2026
• Last Update Submitted That Met QC Criteria: September 3, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Nutrition Disorders; Metabolic Diseases; Overnutrition; Body Weight; Glucose Metabolism Disorders; Diabetes Mellitus; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Signs and Symptoms; Overweight; Obesity; Diabetes Mellitus, Type 2; Substandard Drugs; Pharmaceutical Preparations; orforglipron
• Other Study ID Numbers: 18560 (City of Hope Comprehensive Cancer Center); J2A-MC-GZGQ (Other Identifier: Eli Lilly and Company); 2022-502837-24-00 (Other Identifier: Eli Lilly and Company); U1111-1289-8799 (Other Identifier: UTN Number)

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

Time Frame:

Data 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