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

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

Status
Completed
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04881760
Enrollment
338
Registered
2021-05-11
Start date
2021-05-20
Completion date
2022-11-22
Last updated
2023-09-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obesity, Overweight

Keywords

Nutritional or Metabolism Disorder, Weight Loss, Overnutrition, Incretins, Hormones, Physiological Effects of Drugs

Brief summary

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.

Interventions

DRUGLY3437943

Administered SC

DRUGPlacebo

Administered SC

Sponsors

Eli Lilly and Company
Lead SponsorINDUSTRY

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No

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)

Design outcomes

Primary

MeasureTime frameDescription
Mean Percent Change From Baseline in Body WeightBaseline, Week 24Least 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.

Secondary

MeasureTime frameDescription
Percentage of Participants Who Achieve ≥ 5% Body Weight ReductionWeek 24Percentage 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.
Percentage of Participants Who Achieve ≥ 10% Body Weight ReductionWeek 24Percentage 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.
Percentage of Participants Who Achieve ≥ 15% Body Weight ReductionWeek 24Percentage 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.
Mean Percent Change From Baseline in Body WeightBaseline, Week 48LS 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.
Mean Change From Baseline in BMIBaseline, Week 24LS 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.
Mean Change From Baseline in Waist CircumferenceBaseline, Week 24LS 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.
Mean Change From Baseline in Body WeightBaseline, Week 24LS 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.

Countries

Puerto Rico, United States

Participant flow

Pre-assignment details

Four maintenance doses of LY3437943 were evaluated in the trial: 1, 4, 8, and 12 milligrams (mg). Dose escalation to improve gastrointestinal (GI) tolerability occured in certain treatment groups up to Week 12 by increasing the volume of administered study drug (or placebo) during the 48-week double-blind, placebo-controlled treatment period.

Participants by arm

ArmCount
Placebo
Participants received placebo matched to LY3437943 administered as SC injection QW.
70
1 mg LY3437943
Participants received 1 mg LY3437943 administered as SC injection QW.
69
4 mg LY3437943 (2 mg)
Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 administered as SC injection QW.
33
4 mg LY3437943
Participants received 4 mg LY3437943 administered as SC injection QW.
34
8 mg LY3437943 (2 mg)
Participants received 2 mg LY3437943 starting dose followed by 4 mg LY3437943 and then 8 mg LY3437943 administered as SC injection QW.
35
8 mg LY343794 (4 mg)
Participants received 4 mg LY3437943 starting dose followed by 8 mg LY3437943 administered as SC injection QW.
35
12 mg LY3437943 (2 mg)
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.
62
Total338

Withdrawals & dropouts

PeriodReasonFG000FG001FG002FG003FG004FG005FG006
Overall StudyAdverse Event0110112
Overall StudyDeath0001000
Overall StudyInadvertent Enrollment2000000
Overall StudyLost to Follow-up5751244
Overall StudyRandomized but Never Treated0001000
Overall StudySite Closure0001000
Overall StudyWithdrawal by Subject13114212

Baseline characteristics

Characteristic1 mg LY34379434 mg LY3437943 (2 mg)4 mg LY34379438 mg LY3437943 (2 mg)Placebo8 mg LY343794 (4 mg)12 mg LY3437943 (2 mg)Total
Age, Continuous50.60 years
STANDARD_DEVIATION 13.3
50.80 years
STANDARD_DEVIATION 11.88
46.80 years
STANDARD_DEVIATION 14.1
46.10 years
STANDARD_DEVIATION 13.52
48.00 years
STANDARD_DEVIATION 12.54
48.70 years
STANDARD_DEVIATION 11.14
45.80 years
STANDARD_DEVIATION 12.18
48.20 years
STANDARD_DEVIATION 12.73
Baseline Body Mass Index (BMI)37.49 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 5.85
37.27 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 5.87
37.39 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 4.66
37.37 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 6.04
37.31 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 5.9
36.96 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 5.49
37.42 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 5.98
37.34 kilograms per meter squared (kg/m^2)
STANDARD_DEVIATION 5.71
Baseline Body Weight106.36 kilograms (kg)
STANDARD_DEVIATION 19.84
108.04 kilograms (kg)
STANDARD_DEVIATION 26.31
107.01 kilograms (kg)
STANDARD_DEVIATION 21.29
106.50 kilograms (kg)
STANDARD_DEVIATION 21.55
109.21 kilograms (kg)
STANDARD_DEVIATION 20.88
108.63 kilograms (kg)
STANDARD_DEVIATION 20.88
107.97 kilograms (kg)
STANDARD_DEVIATION 21.69
107.73 kilograms (kg)
STANDARD_DEVIATION 21.35
Ethnicity (NIH/OMB)
Hispanic or Latino
23 Participants9 Participants14 Participants15 Participants22 Participants12 Participants22 Participants117 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
46 Participants24 Participants20 Participants20 Participants47 Participants23 Participants40 Participants220 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants0 Participants1 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants1 Participants0 Participants0 Participants0 Participants1 Participants2 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants1 Participants2 Participants0 Participants1 Participants4 Participants
Race (NIH/OMB)
Black or African American
6 Participants4 Participants2 Participants4 Participants8 Participants1 Participants2 Participants27 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants1 Participants0 Participants1 Participants1 Participants2 Participants5 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants0 Participants0 Participants0 Participants0 Participants0 Participants0 Participants1 Participants
Race (NIH/OMB)
White
61 Participants29 Participants30 Participants30 Participants59 Participants33 Participants56 Participants298 Participants
Region of Enrollment
United States
69 participants33 participants34 participants35 participants70 participants35 participants62 participants338 participants
Sex: Female, Male
Female
33 Participants16 Participants16 Participants17 Participants34 Participants17 Participants30 Participants163 Participants
Sex: Female, Male
Male
36 Participants17 Participants18 Participants18 Participants36 Participants18 Participants32 Participants175 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
EG002
affected / at risk
EG003
affected / at risk
EG004
affected / at risk
EG005
affected / at risk
EG006
affected / at risk
deaths
Total, all-cause mortality
0 / 700 / 690 / 331 / 330 / 350 / 350 / 62
other
Total, other adverse events
40 / 7046 / 6922 / 3324 / 3326 / 3531 / 3552 / 62
serious
Total, serious adverse events
3 / 703 / 690 / 332 / 331 / 352 / 352 / 62

Outcome results

Primary

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.

Time frame: Baseline, Week 24

Population: All randomized participants who had baseline and at least one post-baseline body weight value, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Percent Change From Baseline in Body Weight-1.55 percent changeStandard Error 0.54
1 mg LY3437943Mean Percent Change From Baseline in Body Weight-7.18 percent changeStandard Error 0.67
4 mg LY3437943 (2 mg)Mean Percent Change From Baseline in Body Weight-12.00 percent changeStandard Error 0.71
4 mg LY3437943Mean Percent Change From Baseline in Body Weight-13.80 percent changeStandard Error 0.97
8 mg LY3437943 (2 mg)Mean Percent Change From Baseline in Body Weight-16.64 percent changeStandard Error 0.74
8 mg LY3437943 (4 mg)Mean Percent Change From Baseline in Body Weight-18.26 percent changeStandard Error 0.95
12 mg LY3437943 (2 mg)Mean Percent Change From Baseline in Body Weight-17.39 percent changeStandard Error 0.69
p-value: <0.00195% CI: [-7.34, -3.94]Mixed Models Analysis
p-value: <0.00195% CI: [-12.21, -8.7]Mixed Models Analysis
p-value: <0.00195% CI: [-14.42, -10.08]Mixed Models Analysis
p-value: <0.00195% CI: [-16.9, -13.3]Mixed Models Analysis
p-value: <0.00195% CI: [-18.86, -14.58]Mixed Models Analysis
p-value: <0.00195% CI: [-17.57, -14.13]Mixed Models Analysis
Secondary

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.

Time frame: Baseline, Week 48

Population: All randomized participants who had baseline and at least one post-baseline BMI value, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Change From Baseline in BMI-0.72 kg/m^2Standard Error 0.29
1 mg LY3437943Mean Change From Baseline in BMI-3.22 kg/m^2Standard Error 0.37
4 mg LY3437943 (2 mg)Mean Change From Baseline in BMI-6.14 kg/m^2Standard Error 0.65
4 mg LY3437943Mean Change From Baseline in BMI-6.67 kg/m^2Standard Error 0.59
8 mg LY3437943 (2 mg)Mean Change From Baseline in BMI-8.12 kg/m^2Standard Error 0.55
8 mg LY3437943 (4 mg)Mean Change From Baseline in BMI-9.02 kg/m^2Standard Error 0.57
12 mg LY3437943 (2 mg)Mean Change From Baseline in BMI-9.14 kg/m^2Standard Error 0.46
p-value: <0.00195% CI: [-3.42, -1.57]Mixed Models Analysis
p-value: <0.00195% CI: [-6.81, -4.03]Mixed Models Analysis
p-value: <0.00195% CI: [-7.23, -4.67]Mixed Models Analysis
p-value: <0.00195% CI: [-8.62, -6.18]Mixed Models Analysis
p-value: <0.00195% CI: [-9.55, -7.05]Mixed Models Analysis
p-value: <0.00195% CI: [-9.49, -7.35]Mixed Models Analysis
Secondary

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.

Time frame: Baseline, Week 24

Population: All randomized participants who had baseline and at least one post-baseline BMI value, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Change From Baseline in BMI-0.49 kg/m^2Standard Error 0.21
1 mg LY3437943Mean Change From Baseline in BMI-2.64 kg/m^2Standard Error 0.26
4 mg LY3437943 (2 mg)Mean Change From Baseline in BMI-4.47 kg/m^2Standard Error 0.28
4 mg LY3437943Mean Change From Baseline in BMI-5.13 kg/m^2Standard Error 0.36
8 mg LY3437943 (2 mg)Mean Change From Baseline in BMI-6.15 kg/m^2Standard Error 0.27
8 mg LY3437943 (4 mg)Mean Change From Baseline in BMI-6.84 kg/m^2Standard Error 0.36
12 mg LY3437943 (2 mg)Mean Change From Baseline in BMI-6.44 kg/m^2Standard Error 0.25
p-value: <0.00195% CI: [-2.8, -1.5]Mixed Models Analysis
p-value: <0.00195% CI: [-4.66, -3.29]Mixed Models Analysis
p-value: <0.00195% CI: [-5.46, -3.82]Mixed Models Analysis
p-value: <0.00195% CI: [-6.34, -4.99]Mixed Models Analysis
p-value: <0.00195% CI: [-7.17, -5.53]Mixed Models Analysis
p-value: <0.00195% CI: [-6.59, -5.32]Mixed Models Analysis
Secondary

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.

Time frame: Baseline, Week 24

Population: All randomized participants who had baseline and at least one post-baseline value for body weight, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Change From Baseline in Body Weight-1.27 kilograms (kg)Standard Error 0.63
1 mg LY3437943Mean Change From Baseline in Body Weight-7.72 kilograms (kg)Standard Error 0.73
4 mg LY3437943 (2 mg)Mean Change From Baseline in Body Weight-12.59 kilograms (kg)Standard Error 0.81
4 mg LY3437943Mean Change From Baseline in Body Weight-14.79 kilograms (kg)Standard Error 1.09
8 mg LY3437943 (2 mg)Mean Change From Baseline in Body Weight-17.70 kilograms (kg)Standard Error 0.79
8 mg LY3437943 (4 mg)Mean Change From Baseline in Body Weight-19.75 kilograms (kg)Standard Error 1.08
12 mg LY3437943 (2 mg)Mean Change From Baseline in Body Weight-18.53 kilograms (kg)Standard Error 0.71
p-value: <0.00195% CI: [-8.36, -4.56]Mixed Models Analysis
p-value: <0.00195% CI: [-13.34, -9.3]Mixed Models Analysis
p-value: <0.00195% CI: [-15.99, -11.05]Mixed Models Analysis
p-value: <0.00195% CI: [-18.41, -14.45]Mixed Models Analysis
p-value: <0.00195% CI: [-20.93, -16.04]Mixed Models Analysis
p-value: <0.00195% CI: [-19.11, -15.4]Mixed Models Analysis
Secondary

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.

Time frame: Baseline, Week 48

Population: All randomized participants who had baseline and at least one post-baseline value for body weight, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Change From Baseline in Body Weight-1.84 kgStandard Error 0.83
1 mg LY3437943Mean Change From Baseline in Body Weight-9.37 kgStandard Error 1.06
4 mg LY3437943 (2 mg)Mean Change From Baseline in Body Weight-17.32 kgStandard Error 1.78
4 mg LY3437943Mean Change From Baseline in Body Weight-19.13 kgStandard Error 1.8
8 mg LY3437943 (2 mg)Mean Change From Baseline in Body Weight-23.52 kgStandard Error 1.61
8 mg LY3437943 (4 mg)Mean Change From Baseline in Body Weight-25.88 kgStandard Error 1.68
12 mg LY3437943 (2 mg)Mean Change From Baseline in Body Weight-26.17 kgStandard Error 1.33
p-value: <0.00195% CI: [-10.18, -4.88]Mixed Models Analysis
p-value: <0.00195% CI: [-19.35, -11.6]Mixed Models Analysis
p-value: <0.00195% CI: [-21.19, -13.39]Mixed Models Analysis
p-value: <0.00195% CI: [-25.25, -18.12]Mixed Models Analysis
p-value: <0.00195% CI: [-27.72, -20.36]Mixed Models Analysis
p-value: <0.00195% CI: [-27.4, -21.27]Mixed Models Analysis
Secondary

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.

Time frame: Baseline, Week 48

Population: All randomized participants who had baseline and at least one post-baseline waist circumference value, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Change From Baseline in Waist Circumference-2.64 cmStandard Error 0.99
1 mg LY3437943Mean Change From Baseline in Waist Circumference-6.49 cmStandard Error 1.12
4 mg LY3437943 (2 mg)Mean Change From Baseline in Waist Circumference-14.58 cmStandard Error 1.56
4 mg LY3437943Mean Change From Baseline in Waist Circumference-14.87 cmStandard Error 1.73
8 mg LY3437943 (2 mg)Mean Change From Baseline in Waist Circumference-18.53 cmStandard Error 1.46
8 mg LY3437943 (4 mg)Mean Change From Baseline in Waist Circumference-18.50 cmStandard Error 1.52
12 mg LY3437943 (2 mg)Mean Change From Baseline in Waist Circumference-19.60 cmStandard Error 1.29
p-value: 0.0195% CI: [-6.77, -0.91]Mixed Models Analysis
p-value: <0.00195% CI: [-15.54, -8.33]Mixed Models Analysis
p-value: <0.00195% CI: [-16.11, -8.33]Mixed Models Analysis
p-value: <0.00195% CI: [-19.33, -12.43]Mixed Models Analysis
p-value: <0.00195% CI: [-19.39, -12.31]Mixed Models Analysis
p-value: <0.00195% CI: [-20.13, -13.78]Mixed Models Analysis
Secondary

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.

Time frame: Baseline, Week 24

Population: All randomized participants who had baseline and at least one post-baseline waist circumference value, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Change From Baseline in Waist Circumference-2.60 centimeters (cm)Standard Error 0.8
1 mg LY3437943Mean Change From Baseline in Waist Circumference-5.43 centimeters (cm)Standard Error 0.94
4 mg LY3437943 (2 mg)Mean Change From Baseline in Waist Circumference-10.33 centimeters (cm)Standard Error 1.05
4 mg LY3437943Mean Change From Baseline in Waist Circumference-12.55 centimeters (cm)Standard Error 1
8 mg LY3437943 (2 mg)Mean Change From Baseline in Waist Circumference-13.74 centimeters (cm)Standard Error 1.04
8 mg LY3437943 (4 mg)Mean Change From Baseline in Waist Circumference-14.99 centimeters (cm)Standard Error 0.98
12 mg LY3437943 (2 mg)Mean Change From Baseline in Waist Circumference-14.33 centimeters (cm)Standard Error 0.86
p-value: 0.02295% CI: [-5.23, -0.41]Mixed Models Analysis
p-value: <0.00195% CI: [-10.32, -5.13]Mixed Models Analysis
p-value: <0.00195% CI: [-12.47, -7.43]Mixed Models Analysis
p-value: <0.00195% CI: [-13.72, -8.56]Mixed Models Analysis
p-value: <0.00195% CI: [-14.87, -9.9]Mixed Models Analysis
p-value: <0.00195% CI: [-14.04, -9.43]Mixed Models Analysis
Secondary

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.

Time frame: Baseline, Week 48

Population: All randomized participants who had baseline and at least one post-baseline body weight value, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (LEAST_SQUARES_MEAN)Dispersion
PlaceboMean Percent Change From Baseline in Body Weight-2.11 percent changeStandard Error 0.73
1 mg LY3437943Mean Percent Change From Baseline in Body Weight-8.67 percent changeStandard Error 0.95
4 mg LY3437943 (2 mg)Mean Percent Change From Baseline in Body Weight-16.32 percent changeStandard Error 1.58
4 mg LY3437943Mean Percent Change From Baseline in Body Weight-17.83 percent changeStandard Error 1.53
8 mg LY3437943 (2 mg)Mean Percent Change From Baseline in Body Weight-21.72 percent changeStandard Error 1.41
8 mg LY3437943 (4 mg)Mean Percent Change From Baseline in Body Weight-23.88 percent changeStandard Error 1.51
12 mg LY3437943 (2 mg)Mean Percent Change From Baseline in Body Weight-24.22 percent changeStandard Error 1.24
p-value: <0.00195% CI: [-8.94, -4.2]Mixed Models Analysis
p-value: <0.00195% CI: [-17.64, -10.78]Mixed Models Analysis
p-value: <0.00195% CI: [-19.05, -12.4]Mixed Models Analysis
p-value: <0.00195% CI: [-22.73, -16.51]Mixed Models Analysis
p-value: <0.00195% CI: [-25.05, -18.51]Mixed Models Analysis
p-value: <0.00195% CI: [-24.92, -19.31]Mixed Models Analysis
Secondary

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.

Time frame: Week 24

Population: All randomized participants who had baseline and at least one post-baseline value for ≥ 10% body weight reduction, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Who Achieve ≥ 10% Body Weight Reduction3 percentage of participants
1 mg LY3437943Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction25 percentage of participants
4 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction59 percentage of participants
4 mg LY3437943Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction72 percentage of participants
8 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction83 percentage of participants
8 mg LY3437943 (4 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction94 percentage of participants
12 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction90 percentage of participants
p-value: <0.00195% CI: [11, 33]Regression, Logistic
p-value: <0.00195% CI: [38, 73]Regression, Logistic
p-value: <0.00195% CI: [53, 85]Regression, Logistic
p-value: <0.00195% CI: [66, 93]Regression, Logistic
p-value: <0.00195% CI: [83, 100]Regression, Logistic
p-value: <0.00195% CI: [78, 96]Regression, Logistic
Secondary

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.

Time frame: Week 48

Population: All randomized participants who had baseline and at least one post-baseline value for ≥ 10% body weight reduction, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Who Achieve ≥ 10% Body Weight Reduction9 percentage of participants
1 mg LY3437943Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction27 percentage of participants
4 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction73 percentage of participants
4 mg LY3437943Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction76 percentage of participants
8 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction90 percentage of participants
8 mg LY3437943 (4 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction91 percentage of participants
12 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 10% Body Weight Reduction93 percentage of participants
p-value: 0.00895% CI: [5, 31]Regression, Logistic
p-value: <0.00195% CI: [48, 81]Regression, Logistic
p-value: <0.00195% CI: [51, 84]Regression, Logistic
p-value: <0.00195% CI: [69, 94]Regression, Logistic
p-value: <0.00195% CI: [71, 94]Regression, Logistic
p-value: <0.00195% CI: [74, 94]Regression, Logistic
Secondary

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.

Time frame: Week 24

Population: All randomized participants who had baseline and at least one post-baseline value for ≥ 15% body weight reduction, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Who Achieve ≥ 15% Body Weight Reduction1 percentage of participants
1 mg LY3437943Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction10 percentage of participants
4 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction29 percentage of participants
4 mg LY3437943Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction44 percentage of participants
8 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction51 percentage of participants
8 mg LY3437943 (4 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction68 percentage of participants
12 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction70 percentage of participants
p-value: 0.02995% CI: [1, 17]Regression, Logistic
p-value: <0.00195% CI: [11, 43]Regression, Logistic
p-value: <0.00195% CI: [26, 60]Regression, Logistic
p-value: <0.00195% CI: [33, 66]Regression, Logistic
p-value: <0.00195% CI: [51, 83]Regression, Logistic
p-value: <0.00195% CI: [56, 80]Regression, Logistic
Secondary

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.

Time frame: Week 48

Population: All randomized participants who had baseline and at least one post-baseline value for ≥ 15% body weight reduction, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Who Achieve ≥ 15% Body Weight Reduction2 percentage of participants
1 mg LY3437943Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction16 percentage of participants
4 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction55 percentage of participants
4 mg LY3437943Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction64 percentage of participants
8 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction73 percentage of participants
8 mg LY3437943 (4 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction77 percentage of participants
12 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 15% Body Weight Reduction83 percentage of participants
p-value: 0.00295% CI: [6, 24]Regression, Logistic
p-value: <0.00195% CI: [36, 70]Regression, Logistic
p-value: <0.00195% CI: [47, 79]Regression, Logistic
p-value: <0.00195% CI: [55, 87]Regression, Logistic
p-value: <0.00195% CI: [62, 89]Regression, Logistic
p-value: <0.00195% CI: [71, 92]Regression, Logistic
Secondary

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.

Time frame: Week 48

Population: All randomized participants who had baseline and at least one post-baseline value for ≥ 5% body weight reduction, excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Who Achieve ≥ 5% Body Weight Reduction27 percentage of participants
1 mg LY3437943Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction64 percentage of participants
4 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction87 percentage of participants
4 mg LY3437943Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction97 percentage of participants
8 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction100 percentage of participants
8 mg LY3437943 (4 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction100 percentage of participants
12 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction100 percentage of participants
p-value: <0.00195% CI: [20, 54]Regression, Logistic
p-value: <0.00195% CI: [44, 76]Regression, Logistic
p-value: <0.00195% CI: [57, 83]Regression, Logistic
p-value: <0.00195% CI: [62, 84]Regression, Logistic
p-value: <0.00195% CI: [62, 84]Regression, Logistic
p-value: <0.00195% CI: [67, 84]Regression, Logistic
Secondary

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.

Time frame: Week 24

Population: All randomized participants who had baseline and at least one post-baseline value for ≥ 5% body weight reduction excluding participants discontinuing study drug due to inadvertent enrollment and data after discontinuation of study drug.

ArmMeasureValue (NUMBER)
PlaceboPercentage of Participants Who Achieve ≥ 5% Body Weight Reduction26 percentage of participants
1 mg LY3437943Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction59 percentage of participants
4 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction87 percentage of participants
4 mg LY3437943Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction94 percentage of participants
8 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction100 percentage of participants
8 mg LY3437943 (4 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction100 percentage of participants
12 mg LY3437943 (2 mg)Percentage of Participants Who Achieve ≥ 5% Body Weight Reduction97 percentage of participants
p-value: <0.00195% CI: [17, 49]Regression, Logistic
p-value: <0.00195% CI: [45, 77]Regression, Logistic
p-value: <0.00195% CI: [54, 81]Regression, Logistic
p-value: <0.00195% CI: [63, 85]Regression, Logistic
p-value: <0.00195% CI: [63, 85]Regression, Logistic
p-value: <0.00195% CI: [59, 82]Regression, Logistic

Source: ClinicalTrials.gov · Data processed: Feb 9, 2026