A Study of LY3437943 in Participants Who Have Obesity or Are Overweight

Study Overview
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Brief Summary
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This is a study of LY3437943 in participants who have obesity or are overweight. The main purpose is to learn more about how LY3437943 affects body weight loss. The study will last about 18 months and may include up to 18 visits.

Official Title
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A Phase 2 Study of Once-Weekly LY3437943 Compared With Placebo in Participants Who Have Obesity or Are Overweight With Weight-Related Comorbidities

Conditions
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Obesity, Overweight

Intervention / Treatment
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* Drug: LY3437943
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must have a Body Mass Index (BMI) ) ≥30 and ≤50 kilograms per square meter (kg/m²), or ≥27 kg/m² and <30 kg/m², with at least one of the following comorbidities: hypertension, dyslipidemia, cardiovascular disease Participants must be willing to learn how to self-inject study drug or receive an injection from a trained individual if visually impaired or with physical limitations, and follow study procedures for the duration of the study, including, but not limited to, follow lifestyle advice (for example, dietary changes and physical activity plan), maintain a study drug administration log, and complete required questionnaires Exclusion Criteria: Participants must not have type 1 or type 2 diabetes mellitus Participants must not have had an increase or decrease in body weight > more than 5 kg (11 pounds) within the past 3 months Participants must not have had surgery for obesity or plan to have such surgery during the study Participants must not be using medications that promote weight loss or cause weight gain Participants must not drink excessive amounts of alcohol (more than 14 units a week for women or more than 21 units a week for men) Participants must not have used marijuana within the last 3 months. Participants must not have heart attack, stroke, or hospitalization for congestive heart failure in the past 3 months Participants must not have active cancer within the last 5 years Participants must not have uncontrolled high blood pressure Participants must not have liver disease other than non-alcoholic fatty liver disease Participants must not have renal impairment with estimated glomerular filtration rate (eGFR) <45 mL/min/1.73 m2 Participants must not have a history of acute or chronic pancreatitis symptomatic gallbladder disease or documented human immunodeficiency virus infection Participants must not have a major problem with depression or other mental illness within the last 2 years Participants must not have family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma (family is defined as a first degree relative) Female participants must not be pregnant, breast-feeding, or intend to become pregnant or of childbearing potential and not using adequate contraceptive method (adequate contraceptive measures as required by local regulation or practice)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants received placebo matched to LY3437943 administered as subcutaneous (SC) injection once-weekly (QW). | Drug: Placebo<br>* Administered SC<br>|
| Experimental: 1 milligram (mg) LY3437943<br>Participants received 1 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 4 mg LY3437943 (2 mg)<br>Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 4 mg LY3437943<br>Participants received 4 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 8 mg LY3437943 (2 mg)<br>Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 and then 8 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 8 mg LY3437943 (4 mg)<br>Participants received 4 mg LY3437943 starting dose followed by 8 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|
| Experimental: 12 mg LY3437943 (2 mg)<br>Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943, 8 mg LY3437943 and then 12 mg LY3437943 administered as SC injection QW. | Drug: LY3437943<br>* Administered SC<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline in Body Weight | Least squares (LS) means were calculated using a mixed-effects model for repeated measures (MMRM) for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Percent Change From Baseline in Body Weight | LS means were calculated using a MMRM model for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 48 | 
| Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction | Percentage of participants who achieve ≥ 5% body weight reduction in LY3437943 relative to placebo. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<36 kilograms per square meter (kg/m2), ≥36 kg/m2] and sex [female, male] as fixed effects, and baseline body weight as a covariate. | Week 24 | 
| Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction | Percentage of participants who achieve ≥ 5% body weight reduction in LY3437943 relative to placebo. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<36 kg/m2, ≥36 kg/m2] and sex [female, male] as fixed effects, and baseline body weight as a covariate. | Week 48 | 
| Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction | Percentage of participants who achieve ≥ 10% body weight reduction in LY3437943 relative to placebo. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<36 kg/m2, ≥36 kg/m2] and sex [female, male] as fixed effects, and baseline body weight as a covariate. | Week 24 | 
| Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction | Percentage of participants who achieve ≥ 10% body weight reduction in LY3437943 relative to placebo. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<36 kg/m2, ≥36 kg/m2] and sex [female, male] as fixed effects, and baseline body weight as a covariate. | Week 48 | 
| Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction | Percentage of participants who achieve ≥ 15% body weight reduction in LY3437943 relative to placebo. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<36 kg/m2, ≥36 kg/m2] and sex [female, male] as fixed effects, and baseline body weight as a covariate. | Week 24 | 
| Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction | Percentage of participants who achieve ≥ 15% body weight reduction in LY3437943 relative to placebo. Estimated percentage was determined by logistic regression model with an intercept term, treatment group, baseline BMI stratum [<36 kg/m2, ≥36 kg/m2] and sex [female, male] as fixed effects, and baseline body weight as a covariate. | Week 48 | 
| Mean Change From Baseline in Body Weight | LS means were calculated using a MMRM model for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 24 | 
| Mean Change From Baseline in Body Weight | LS means were calculated using a MMRM model for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 48 | 
| Mean Change From Baseline in BMI | LS means were calculated using a MMRM model for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 24 | 
| Mean Change From Baseline in BMI | LS means were calculated using a MMRM model for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 48 | 
| Mean Change From Baseline in Waist Circumference | LS means were calculated using a MMRM model for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 24 | 
| Mean Change From Baseline in Waist Circumference | LS means were calculated using a MMRM model for post-baseline measures: Variable = Treatment*Time + Baseline BMI (< 36kg/m2 vs. >=36 kg/m2)*Time + Sex (Female vs. Male)*Time + Baseline*Time. | Baseline, Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physiological Effects of Drugs, Nutritional or Metabolism Disorder, Weight Loss, Overnutrition, Incretins, Hormones