LY3305677 for Obesity

Recruiting at 70 trial locations

Overseen By Jeffrey A Norton

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Disqualifiers: Type 1 diabetes, Hypertension, Liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

1217 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new treatments for individuals struggling with obesity to assess their safety and effectiveness. Participants will receive one of several treatments, such as LY3305677 (also known as LY900038), LY3549492, or LY3841136, administered as injections or pills. The trial seeks individuals with a body mass index (BMI) of 30 or higher, or those with a BMI of 27 or higher who have a weight-related health issue, and who have maintained a stable weight for the past three months. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that LY3305677, also known as IBI362, is generally safe for individuals who are overweight or have obesity, with a good safety record and few side effects. Most participants did not experience serious harmful effects.

Early studies on LY3549492 have examined its safety and tolerability, suggesting it is generally safe to use. However, because these are early studies, less information is available compared to treatments studied more thoroughly.

LY3841136, another drug tested in this trial, has been studied both alone and with tirzepatide. It is generally well tolerated, meaning most people can take it without major problems. Some studies have shown it can aid weight loss after just one dose.

In summary, current research indicates all three treatments appear safe. While side effects can occur, they are usually not serious. These findings are promising, but more research is needed to fully understand the safety of these drugs. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they offer innovative approaches to tackling obesity beyond the typical lifestyle changes and medications like orlistat, liraglutide, or semaglutide. LY3305677, for example, is unique because it is administered subcutaneously and may offer a novel mechanism of action targeting metabolic pathways. LY3549492, taken orally, provides a potentially easier administration route, which could improve patient compliance. Meanwhile, LY3841136, also administered subcutaneously, is notable for its potential use alongside tirzepatide, possibly enhancing its effectiveness. These treatments hold promise due to their varied delivery methods and potential for new mechanisms of action, which could lead to more effective and convenient options for managing obesity.

What evidence suggests that this trial's treatments could be effective for obesity?

Research has shown that the treatments tested for obesity in this trial have yielded promising results in earlier studies. Participants may receive LY3305677, which functions like semaglutide and has been linked to significant weight loss. Specifically, past studies showed about a 15% reduction in body weight over two years. Another treatment option is LY3549492, a pill that demonstrated an average weight loss of 12.4% in previous research. LY3841136, also under study, has shown potential for weight loss when used alone or with tirzepatide, a well-known weight loss drug. Each treatment targets obesity differently but has effectively reduced body weight in earlier research. ^{5 6 7 8 9}

Who Is on the Research Team?

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

This trial is for adults with obesity, defined as having a BMI ≥30 kg/m², or overweight individuals (BMI ≥27 kg/m² and <30 kg/m²) with weight-related health issues like high blood pressure on medication, cholesterol problems on drugs, heart disease, or sleep apnea. Participants should have maintained their body weight within a 5% range in the past 3 months.

Inclusion Criteria

Your body weight has not changed by more than 5% in the past 3 months before joining the study.

My BMI is between 27 and 30, and I have a weight-related health issue.

You have a BMI of 30 or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive various investigational interventions for chronic weight management as per the intervention-specific appendices (ISAs)

48 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY900038

Trial Overview The study is testing the safety and effectiveness of various potential treatments for chronic weight management. One group will receive an investigational drug called LY3305677 while another group will get a placebo. The interventions are part of separate appendices that can start at different times.

How Is the Trial Designed?

Group I: LY3841136 Obesity ISA LAA2 Experimental Treatment 3 Interventions

Participants will receive LY3841136, tirzepatide and placebo SC. Each ISA will detail the intervention specific analysis.

Group II: LY3841136 Obesity ISA LAA1 Experimental Treatment 2 Interventions

Participants will receive LY3841136 or placebo SC. Each ISA will detail the intervention specific analysis.

Group III: LY3549492 Obesity ISA GN02 Experimental Treatment 2 Interventions

Participants will receive LY3549492 or placebo orally. Each ISA will detail the intervention specific analysis.

Group IV: LY3549492 Obesity ISA GN01 Experimental Treatment 2 Interventions

Participants will receive LY3549492 orally. Each ISA will detail the intervention specific analysis.

Group V: LY3305677 Obesity ISA OXA1 Experimental Treatment 2 Interventions

Participants will receive LY3305677 or placebo subcutaneously (SC). Each ISA will detail the intervention specific analysis.

LY900038 is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Wegovy for:

• Chronic weight management in adults with obesity or overweight with at least one weight-related condition

Approved in United States as Ozempic for:

• Type 2 diabetes mellitus
• Reducing the risk of major adverse cardiovascular events

Approved in United States as Rybelsus for:

• Type 2 diabetes mellitus

Approved in European Union as Semaglutide for:

• Type 2 diabetes mellitus
• Chronic weight management in adults with obesity or overweight with at least one weight-related condition

Approved in Canada as Semaglutide for:

• Type 2 diabetes mellitus
• Chronic weight management in adults with obesity or overweight with at least one weight-related condition

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Published Research Related to This Trial

In a phase 3 trial involving 667 adults with overweight or obesity, oral semaglutide 50 mg taken daily resulted in a significant average weight loss of 15.1% compared to only 2.4% with placebo over 68 weeks, demonstrating its efficacy in weight management.

While semaglutide was effective, it was associated with a higher incidence of adverse events, particularly gastrointestinal issues, affecting 80% of participants, indicating that while it is effective, monitoring for side effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral semaglutide 50 mg taken once per day in adults with overweight or obesity (OASIS 1): a randomised, double-blind, placebo-controlled, phase 3 trial. Knop, FK., Aroda, VR., do Vale, RD., et al.[2023]

Semaglutide 2.4 mg led to significant weight loss in adults with overweight/obesity, achieving a mean change of -15.7% for those on antidepressants compared to -0.2% for placebo, demonstrating its efficacy regardless of antidepressant use.

The safety profile of semaglutide was consistent with previous studies, showing a similar prevalence of adverse events between the semaglutide and placebo groups among participants taking antidepressants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of semaglutide 2.4 mg according to antidepressant use at baseline: A post hoc subgroup analysis. Kushner, RF., Fink-Jensen, A., Frenkel, O., et al.[2023]

Semaglutide, a once-weekly glucagon-like peptide-1 receptor agonist, has been shown to achieve significant and sustained weight loss in individuals with obesity, surpassing results from previous weight-loss medications, and has been approved for use alongside diet and exercise.

Emerging treatments like tirzepatide and cagrilintide are demonstrating even greater weight loss effects than semaglutide, indicating a shift towards more effective 'weight-centric' strategies for managing obesity and related conditions like type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Once-weekly 2.4 mg Semaglutide for Weight Management in Obesity: A Game Changer? Colin, IM., Gérard, KM.[2022]

In a 12-week study involving 72 adults with type 2 diabetes, the multi-receptor agonist LY3437943 demonstrated a good safety profile, with gastrointestinal disorders being the most common side effects.

LY3437943 significantly reduced daily plasma glucose and HbA1c levels, as well as body weight, in a dose-dependent manner, supporting its potential for once-weekly dosing and further development in treating type 2 diabetes and obesity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomised, multiple-ascending dose trial. Urva, S., Coskun, T., Loh, MT., et al.[2022]

In a 20-week trial with 72 adults, once-weekly subcutaneous semaglutide 2.4 mg significantly reduced appetite and energy intake, leading to a 9.9% reduction in body weight compared to only 0.4% with placebo.

Semaglutide improved participants' control over eating and reduced food cravings without causing delayed gastric emptying, indicating its efficacy in managing obesity without adverse effects on gastric function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of semaglutide 2.4 mg once weekly on energy intake, appetite, control of eating, and gastric emptying in adults with obesity. Friedrichsen, M., Breitschaft, A., Tadayon, S., et al.[2021]

Semaglutide, a glucagon-like peptide-1 receptor agonist, has been shown to produce the largest weight loss of any obesity medication, with an average reduction of about 15% of initial body weight over 68 weeks.

In addition to significant weight loss, semaglutide also improves cardiovascular risk factors and physical functioning, making it a promising option for chronic weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for the treatment of obesity. Chao, AM., Tronieri, JS., Amaro, A., et al.[2023]

In two phase III trials involving 2764 participants with overweight or obesity, semaglutide 2.4 mg once weekly significantly improved cardiometabolic risk factors, including reductions in waist circumference, blood pressure, and fasting glucose compared to placebo.

The benefits of semaglutide were not sustained after stopping the treatment, indicating that ongoing administration may be necessary to maintain improvements in health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity: STEP 1 and 4 exploratory analyses. Kosiborod, MN., Bhatta, M., Davies, M., et al.[2023]

Semaglutide, approved by the FDA on June 4, 2021, is the first new drug for chronic weight management in adults with obesity or overweight since 2014, specifically targeting those with a BMI of 27 or greater and at least one weight-related condition.

This medication is intended to be used alongside a weight management program that includes a reduced-calorie diet and increased physical activity, highlighting its role as part of a comprehensive approach to weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity. Mares, AC., Chatterjee, S., Mukherjee, D.[2023]

Obesity is a major public health concern, with projections indicating that over 1.1 billion individuals will be affected by 2030, highlighting the urgent need for effective treatments.

GLP-1 receptor agonists, particularly semaglutide, are at the forefront of clinical development for obesity treatment, showing promise in improving metabolic health and potentially serving as a benchmark for future anti-obesity therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity. Jepsen, MM., Christensen, MB.[2022]

High-dose once-weekly semaglutide has been shown to significantly reduce weight in patients with obesity or overweight, as demonstrated in four phase 3 clinical trials involving various populations, including those with diabetes.

While gastrointestinal side effects were common, semaglutide was generally well tolerated and also led to improvements in cardiometabolic risk factors, such as waist circumference and blood pressure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-Dose Once-Weekly Semaglutide: A New Option for Obesity Management. Bradley, CL., McMillin, SM., Hwang, AY., et al.[2022]

Citations

1. prnewswire.com prnewswire.com/news-releases/novo-nordisk-presents-four-new-analyses-on-oral-semaglutide-25-mg-wegovy-in-a-pill-at-obesityweek-2025-including-demonstrated-reductions-in-cardiovascular-risk-factors-302605329.html

Novo Nordisk presents four new analyses on oral ... A meaningful change in PF score was achieved by most patients (77.3%) taking oral semaglutide 25 mg versus those taking placebo (42.9%).4.

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa2032183

Once-Weekly Semaglutide in Adults with Overweight or ... Analyses from the DXA substudy suggested that semaglutide led to greater reduction in fat mass than lean body mass, a finding consistent with ...

3. novomedlink.com novomedlink.com/obesity/products/treatments/wegovy/efficacy-safety/chronic-weight-management.html

Chronic Weight Management Trial Results | Wegovy ... During the trial, 13% of patients in the Wegovy® arm discontinued treatment compared with 27% in the placebo arm. Missing data were imputed from retrieved ...

4. nature.com nature.com/articles/s41591-022-02026-4

Two-year effects of semaglutide in adults with overweight ... The mean weight loss of ~15% achieved with semaglutide 2.4 mg at week 104 in STEP 5 exceeds weight loss reported at similar time points in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9758543/

Semaglutide for Weight Loss in Obesity Without Diabetes Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight loss with an 11.85% reduction from baseline compared ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39948761/

Safety profile of semaglutide versus placebo in the ... The objective of this study was to assess safety of once-weekly subcutaneous semaglutide 2.4 mg versus placebo, beyond reduction in major adverse ...

7. nejm.org nejm.org/doi/full/10.1056/NEJMoa2307563

Semaglutide and Cardiovascular Outcomes in Obesity ... This trial involved targeted collection of safety data, in which the only adverse events systematically recorded and reported were serious adverse events ...

8. clinicaltrials.gov clinicaltrials.gov/study/NCT03548935

NCT03548935 | STEP 1: Research Study Investigating ... Effect and Safety of Semaglutide 2.4 mg Once-weekly in Subjects With Overweight or Obesity. Conditions. Metabolism and Nutrition DisorderOverweight or Obesity.

9. sciencedirect.com sciencedirect.com/science/article/pii/S2589537021003680

IBI362 (LY3305677), a weekly-dose GLP-1 and glucagon ... In summary, this study demonstrated that IBI362 was well tolerated with an overall good safety profile in Chinese participants with overweight or obesity.