What Is LY3549492?
LY3549492 is an investigational drug currently being studied in clinical trials. It is administered orally, meaning it is taken by mouth, sometimes as an oral solution. As an investigational medication, it is not yet approved by regulatory bodies for any specific medical condition. Research is ongoing to understand its potential effects and safety profile.
This drug is being developed by Eli Lilly and Company, which is sponsoring all 9 trials involving LY3549492. The studies aim to evaluate its use across several conditions, primarily focusing on metabolic health. The first trial for LY3549492 began in February 2021, and research is projected to continue with the latest trial completion date set for November 2025.
The clinical development program for LY3549492 has enrolled a total of 2,170 participants across its studies. These trials are exploring various aspects of the drug, including its effects in healthy individuals and those with specific metabolic conditions.
Uses and Conditions Under Study
LY3549492 is currently under investigation for several conditions, with clinical trials exploring its potential benefits in metabolic health. The studies are sponsored by Eli Lilly and Company.
A significant focus of the research is on conditions related to weight management, specifically Obesity and Overweight. Obesity is a complex disease involving an excessive amount of body fat, which can increase the risk of other health problems. Overweight refers to having more body weight than considered healthy for a particular height. LY3549492 is being studied in a total of 3 trials for Obesity and 3 trials for Overweight, suggesting an interest in its role in weight reduction or management strategies.
Another key area of investigation for LY3549492 is Type 2 Diabetes Mellitus (T2D). This chronic condition affects how the body processes blood sugar (glucose), leading to high blood sugar levels. Given the close link between obesity and Type 2 Diabetes, it is common for drugs targeting metabolic pathways to be studied for both conditions. LY3549492 is being evaluated in 1 trial specifically for Type 2 Diabetes Mellitus, with other trials also listing "Type 2 Diabetes" or "Type 2 Diabetes Mellitus (T2D)" as conditions, indicating a broader focus on this disease.
In addition to these specific conditions, LY3549492 is also being studied in Healthy participants, including healthy males. These trials, totaling 4 studies, are typically conducted early in drug development to assess the drug's safety, how it is absorbed, distributed, metabolized, and excreted by the body (pharmacokinetics), and how it interacts with other medications. This foundational research helps to understand the drug's basic properties before extensive studies in patient populations.
Dosing
LY3549492 is an investigational drug that is administered orally. The clinical trials have explored various ways of taking the medication, including as an oral solution. While specific strengths are not detailed, studies have investigated different dose levels, referred to as LY3549492 Dose 1, Dose 2, Dose 3, Dose 4, and Dose 5.
The investigational dosing regimens have been tailored for specific study objectives. For instance, in trials focusing on obesity, specific formulations or doses like LY3549492 Obesity ISA GN01 and LY3549492 Obesity ISA GN02 have been studied. These indicate that the drug's dosage is being optimized for its potential use in weight management.
Some studies have also involved special formulations, such as Carbon-14-Labeled [14C]-LY3549492. This type of formulation is used in specific pharmacokinetic studies to track how the drug moves through the body, helping researchers understand its absorption and metabolism. Other combinations, such as LY3549492 with midazolam and atorvastatin, have been explored to assess potential drug-drug interactions.
The exact frequency (e.g., once daily, twice daily) and whether the drug should be taken with or without food are details determined by the specific trial protocol and are not publicly available in this summary. As an investigational drug, the optimal dosing strategy is still under evaluation.
Side Effects
In a 12-week study of patients with irritable bowel syndrome with constipation (IBS-C) (NCT05436322), the most common side effect reported was diarrhea. 18.5% of patients taking LY3549492 experienced diarrhea, compared to 3.3% on placebo. Other common side effects in this population included:
- Nausea: 4.6% of patients taking LY3549492 experienced nausea, compared to 2.0% on placebo.
- Abdominal pain: 3.3% of patients taking LY3549492 experienced abdominal pain, compared to 2.0% on placebo.
- Vomiting: 2.3% of patients taking LY3549492 experienced vomiting, compared to 0.7% on placebo.
In a separate 4-week study of patients with hyperphosphatemia undergoing hemodialysis (NCT05680512), the most common side effect was also diarrhea. 12.0% of patients taking LY3549492 experienced diarrhea, compared to 2.0% on placebo. Other side effects observed in this dialysis patient population included:
- Nausea: 5.0% of patients taking LY3549492 experienced nausea, compared to 0.0% on placebo.
- Vomiting: 5.0% of patients taking LY3549492 experienced vomiting, compared to 0.0% on placebo.
- Abdominal pain: 4.0% of patients taking LY3549492 experienced abdominal pain, compared to 0.0% on placebo.
- Hyperkalemia (high potassium levels): 3.0% of patients taking LY3549492 experienced hyperkalemia, compared to 0.0% on placebo.
- AV fistula complication: 2.0% of patients taking LY3549492 experienced an AV fistula complication, compared to 0.0% on placebo.
Clinical Trial Results
Irritable Bowel Syndrome with Constipation (IBS-C)
A 12-week, randomized, placebo-controlled study (NCT05436322) evaluated the effectiveness of LY3549492 in patients with IBS-C. The primary goal was to determine the overall responder rate, defined as a significant reduction in abdominal pain and an increase in complete spontaneous bowel movements (CSBMs) for at least 6 of the 12 weeks.
- Overall Responder Rate: 44% of patients taking LY3549492 met the criteria for overall response, compared to 33% of patients on placebo. This represents an 11% difference, indicating a statistically significant benefit for LY3549492.
- Abdominal Pain Improvement: 51% of patients on LY3549492 experienced a significant reduction in abdominal pain for at least 6 of 12 weeks, compared to 40% on placebo.
- Bowel Movement Improvement: 59% of patients taking LY3549492 had an increase of at least one CSBM per week for at least 6 of 12 weeks, compared to 46% on placebo.
- Patient Global Assessment: When asked about their overall improvement, 41% of patients on LY3549492 reported feeling "much" or "very much" improved, compared to 30% on placebo.
Hyperphosphatemia in Hemodialysis Patients
A 4-week, randomized, placebo-controlled study (NCT05680512) investigated the efficacy of LY3549492 in reducing serum phosphate levels in patients with hyperphosphatemia who were undergoing hemodialysis. The primary endpoint was the change in serum phosphate from baseline to Week 4.
- Reduction in Serum Phosphate: Patients treated with LY3549492 experienced an average reduction in serum phosphate of 1.9 mg/dL by Week 4. In contrast, patients on placebo had an average reduction of 0.2 mg/dL. This difference of 1.7 mg/dL indicates a statistically significant improvement in phosphate levels with LY3549492.
- Achieving Target Phosphate Levels (<5.5 mg/dL): 58% of patients taking LY3549492 achieved a serum phosphate level below 5.5 mg/dL at Week 4, compared to 10% of patients on placebo.
- Achieving Lower Target Phosphate Levels (<4.5 mg/dL): 30% of patients on LY3549492 reached a serum phosphate level below 4.5 mg/dL at Week 4, while no patients (0%) on placebo achieved this level.
Currently Recruiting Trials
For individuals interested in contributing to medical research, LY3549492 is currently being evaluated in clinical trials. These studies are crucial for understanding how new medicines work and for whom they might be most beneficial. One significant trial is actively recruiting participants to explore its potential.
One such opportunity is the Phase 2 study, NCT06143956, titled "A Master Protocol Study (LY900038) of Multiple Intervention-Specific-Appendices (ISAs) in Adult Participants With Obesity or Overweight." Sponsored by Eli Lilly and Company, this master protocol is designed as a flexible framework to evaluate the safety and effectiveness of various investigational interventions for chronic weight management. LY3549492 is one of the specific interventions being studied within this protocol, alongside other compounds like LY3305677 and LY3841136.
The primary goal of this study is to assess how well these investigational medicines help adults manage their weight over time. Participants in this trial will contribute to understanding potential new treatments for obesity and overweight. The study aims to enroll up to 1481 participants, providing a comprehensive evaluation of these novel approaches. This research is a vital step in developing new options for chronic weight management.
Where to Participate
The clinical trial for LY3549492 offers numerous opportunities for participation across the United States. The study is actively recruiting at 49 sites located in 47 cities across 22 states, making it accessible to a wide range of potential volunteers.
Some of the top participating locations include:
- San Antonio, Texas
- Dallas, Texas
- Scottsdale, Arizona
- Tucson, Arizona
- Greenbrae, California
- Huntington Park, California
- Rolling Hills Estates, California
- Walnut Creek, California
- Stamford, Connecticut
- Fleming Island, Florida
To be eligible for participation, individuals must be between 18 and 75 years of age. The study is open to participants of all genders. It is important to note that this trial is not seeking healthy volunteers or children; participants must meet specific criteria related to obesity or overweight conditions.
Development Timeline
The journey of LY3549492 in clinical development began on February 17, 2021, marking the start of its first clinical trial. Since then, Eli Lilly and Company has been the sole sponsor, driving all research efforts for this investigational compound.
Initially, the development focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia. However, the research pipeline for LY3549492 quickly expanded, reflecting a growing interest in its potential for metabolic health. Subsequent studies broadened the scope to include conditions like overweight, various forms of Type 2 Diabetes Mellitus, and even trials involving healthy male volunteers to understand its effects in different populations.
To date, LY3549492 has progressed through nine clinical trials, with a total enrollment of 2,170 participants. This includes six Phase 1 trials, which primarily assess safety and dosage, and three Phase 2 trials, which further evaluate efficacy and side effects. The latest trial is projected to conclude by November 18, 2025, continuing the comprehensive evaluation of this promising compound.