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Trial · Interventional

CompletedPhase 3Results postedRegistry data

A Study of Orforglipron in Adult Participants With Obesity or Overweight and Type 2 Diabetes

Short name ATTAIN-2

NCTNCT05872620 (opens ClinicalTrials.gov in a new tab)Other id18560Other idJ2A-MC-GZGQOther id2022-502837-24-00Other idU1111-1289-8799
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
1,613 participants (actual)
Sponsor
Eli Lilly and Company · Industry
Design
Randomized · Double masking
Countries
11 countries

United States, Argentina, Australia, Brazil, China, Czechia, Germany, Greece, India, Puerto Rico, South Korea

Start
5 Jun 2023
Primary completion
8 Aug 2025
Completion
8 Aug 2025
First posted
24 May 2023
Last update posted
4 Sept 2026
Conditions
Obesity · Overweight · Type 2 Diabetes

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
2023202420252026
  1. Ph 3

    ATTAIN-2

    NCT05872620

    5 Jun 2023 to 8 Aug 2025

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • OrforglipronDrug
  • PlaceboDrug

Arms4

  • 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.

  • 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.

  • 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.

  • 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.

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Percent Change From Baseline in Body Weight

    Time frame · Baseline, Week 72

    Registry description

    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.

Secondary outcomes(14)

  1. Percentage of Participants Who Achieved With Greater Than or Equal to (≥) 5% Body Weight Reduction From Baseline

    Time frame · Baseline to Week 72

    Registry description

    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).

  2. Percentage of Participants Who Achieved ≥10% Body Weight Reduction From Baseline

    Time frame · Baseline to Week 72

    Registry description

    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).

  3. Percentage of Participants Who Achieved ≥15% Body Weight Reduction From Baseline

    Time frame · Baseline to Week 72

    Registry description

    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).

  4. Change From Baseline in Waist Circumference

    Time frame · Baseline, Week 72

    Registry description

    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.

  5. Change From Baseline in Hemoglobin A1c (HbA1c) %

    Time frame · Baseline, Week 72

    Registry description

    * 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.

  6. Change From Baseline in Fasting Serum Glucose (FSG)

    Time frame · Baseline, Week 72

    Registry description

    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.

  7. Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<6.5%)

    Time frame · Baseline to Week 72

    Registry description

    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).

  8. Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<7.0%)

    Time frame · Baseline to Week 72

    Registry description

    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).

  9. Change From Baseline in Systolic Blood Pressure (SBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)

    Time frame · Baseline, Week 72

    Registry description

    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.

  10. Change From Baseline in Diastolic Blood Pressure (DBP) (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)

    Time frame · Baseline, Week 72

    Registry description

    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.

  11. Percent Change From Baseline in Fasting Insulin

    Time frame · Baseline, Week 72

    Registry description

    * 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.

  12. Percent Change From Baseline in Non-High-Density Lipoprotein (Non-HDL) Cholesterol (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)

    Time frame · Baseline, Week 72

    Registry description

    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.

  13. Percent Change From Baseline in Triglycerides (Pooled Doses of Orforglipron 6 mg, 12 mg and 36 mg)

    Time frame · Baseline, Week 72

    Registry description

    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.

  14. 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)

    Time frame · Baseline, Week 72

    Registry description

    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.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeLeast squares mean· Baseline, Week 72

Percent Change From Baseline in Body Weight

GroupValue (percent change)Spread
Placebo-2.210.215
6 mg Orforglipron QD-5.500.356
12 mg Orforglipron QD-7.780.411
36 mg Orforglipron QD-10.540.466
Secondary and other outcome results(7)
Secondary outcomeNumber· Baseline to Week 72

Percentage of Participants Who Achieved With Greater Than or Equal to (≥) 5% Body Weight Reduction From Baseline

GroupValue (Percentage of participants)
Placebo24.4
6 mg Orforglipron QD49.8
12 mg Orforglipron QD60.2
36 mg Orforglipron QD72.8
Secondary outcomeNumber· Baseline to Week 72

Percentage of Participants Who Achieved ≥10% Body Weight Reduction From Baseline

GroupValue (Percentage of participants)
Placebo7.0
6 mg Orforglipron QD23.9
12 mg Orforglipron QD35.5
36 mg Orforglipron QD50.1
Secondary outcomeNumber· Baseline to Week 72

Percentage of Participants Who Achieved ≥15% Body Weight Reduction From Baseline

GroupValue (Percentage of participants)
Placebo1.9
6 mg Orforglipron QD7.3
12 mg Orforglipron QD17.7
36 mg Orforglipron QD28.4
Secondary outcomeLeast squares mean· Baseline, Week 72

Change From Baseline in Waist Circumference

GroupValue (centimeters)Spread
Placebo-2.670.233
6 mg Orforglipron QD-5.640.394
12 mg Orforglipron QD-7.160.422
36 mg Orforglipron QD-9.160.437
Secondary outcomeLeast squares mean· Baseline, Week 72

Change From Baseline in Hemoglobin A1c (HbA1c) %

GroupValue (percentage of HbA1c)Spread
Placebo-0.140.060
6 mg Orforglipron QD-1.290.069
12 mg Orforglipron QD-1.600.058
36 mg Orforglipron QD-1.790.059
Secondary outcomeLeast squares mean· Baseline, Week 72

Change From Baseline in Fasting Serum Glucose (FSG)

GroupValue (milligram per deciliter (mg/dL))Spread
Placebo1.21.90
6 mg Orforglipron QD-33.02.13
12 mg Orforglipron QD-41.11.69
36 mg Orforglipron QD-45.81.79
Secondary outcomeNumber· Baseline to Week 72

Percentage of Participants Who Achieved Hemoglobin A1c (HbA1c) Target Value (<6.5%)

GroupValue (Percentage of participants)
Placebo10.6
6 mg Orforglipron QD56.2
12 mg Orforglipron QD67.5
36 mg Orforglipron QD75.0

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
PlaceboParticipants received matching placebo capsule orally once daily. Treatment was initiated with placebo corresponding to 1 mg equivalent to Orforglipron, with dose escalation every 4 weeks to maintain blinding, and was continued through Week 72, unless dose modification was required.4 / 62855 / 628452 / 628
6 mg Orforglipron QDParticipants 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.0 / 32824 / 328231 / 328
12 mg Orforglipron QDParticipants 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.4 / 33134 / 331262 / 331
36 mg Orforglipron QDParticipants 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.2 / 32135 / 321255 / 321

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2026

8 results

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.

Horn et al. 2026Lancet (London, England)cited by 20

PMID 41275875DOI 10.1016/s0140-6736(25)02165-8PUB-41275875

Full text at the publisher8 results
Publisher pageSee results (8)

PubMed tag: none · 2026

8 results

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.

Horn et al. 2026Obesity pillars

PMID 42577069PMC13453602DOI 10.1016/j.obpill.2026.100301PUB-42577069

Free to read · publisher termsCC BY-NC-ND8 results
Read at sourceSee results (8)

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
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.

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