BI 456906 for Obesity

Recruiting at 558 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: GLP-1R agonists

Disqualifiers: Type 1 diabetes, Gastric abnormalities, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 21

Duration: 2 years and 3 months

4935 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines a medicine called survodutide (also known as BI 456906) to determine if it can help individuals with obesity or overweight reduce their risk of serious heart problems. The study will also assess its effects on factors like blood pressure. Participants will be divided into three groups: two will receive different doses of survodutide, and one will receive a placebo (a non-active substance resembling the medicine). This study targets individuals who have previously tried dieting, have a BMI of 27 or more, and have heart or kidney issues, or at least two weight-related health problems. Participants will visit the study site over a period of up to about two years. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot have used certain diabetes medications called GLP-1R agonists in the last 3 months before joining. It's best to discuss your specific medications with the trial staff.

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

Research has shown that survodutide, the treatment being tested, may aid in weight loss. In earlier studies, participants lost a significant amount of weight, suggesting that this treatment could be effective for those who are overweight or have obesity.

Regarding safety, previous research examined how well people tolerate survodutide. Results so far indicate that most people handle the treatment well. However, like any new treatment, some side effects might occur. These could include mild to moderate reactions, but serious side effects have not been reported in the available data.

This current study involves more participants, allowing researchers to gather more detailed safety information. The treatment uses a combination of compounds often found in medicines for managing weight and blood sugar levels. While this suggests some familiarity with its components, participants should be aware that any side effects will be closely monitored throughout the trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for obesity?

Researchers are excited about survodutide for obesity because it offers a unique approach compared to current treatments. Most existing obesity medications focus on appetite suppression or calorie absorption reduction. Survodutide, however, is a GLP-1/glucagon receptor dual agonist, which not only helps to control appetite but also boosts energy expenditure by increasing metabolism. This dual action could potentially lead to more effective weight loss and improved metabolic health, setting it apart from other treatments that primarily target just one aspect of weight management.

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

Research has shown that survodutide (BI 456906) may aid weight loss in people with obesity. In an earlier study, participants lost nearly 19% of their body weight after using survodutide, highlighting its potential effectiveness. In this trial, participants will receive either varying dosages of survodutide or a placebo to further assess its effects. Researchers are also studying survodutide for potential heart health benefits, given the link between obesity and heart disease. Early results appear promising, but further research is necessary to confirm these benefits. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with a BMI of 27 kg/m2 or more can join this trial if they have cardiovascular disease, chronic kidney disease, or at least two weight-related health issues. They should have tried dieting to lose weight before.

Inclusion Criteria

History of at least one self-reported unsuccessful dietary effort to lose body weight

Have diagnosed and treated Hypertension, Dyslipidaemia, Type 2 Diabetes or NASH/MASH.

You do not have any other exclusionary concomitant conditions, such as severe gastroparesis or gastric outlet obstruction, chronic or acute pancreatitis, heart failure Class IV, recent (past month) acute CV events like a heart attack, stroke, TIA, hospitalization for heart failure, unstable angina, or peripheral artery event, and you do not have a family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2.

Exclusion Criteria

Treatment with any medication for the obesity indication within 3 months before screening; previous or planned (during the trial period) treatment for obesity with surgery or a weight loss device.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive survodutide or placebo injections once a week, with counseling on diet and physical activity

2 years and 3 months

21 visits (in-person), remote visits by video calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 456906

Trial Overview The study tests BI 456906 (survodutide) against a placebo for its effects on cardiovascular safety in overweight individuals. Participants are split into three groups and receive either survodutide or placebo alongside diet and exercise counseling.

How Is the Trial Designed?

Group I: survodutide 6.0 mg Experimental Treatment 1 Intervention

Group II: survodutide 3.6 mg Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Published Research Related to This Trial

Lifestyle changes like diet, exercise, and behavioral therapy are essential for treating obesity, and if these do not lead to a 5% weight loss in 3 to 6 months, medications may be considered for patients with a BMI of 30 or higher, or 27 with related health issues.

Current obesity medications like orlistat, sibutramine, and rimonabant can lead to moderate weight loss and improved cardiovascular health, particularly enhancing glucose metabolism, but their side effects must be carefully evaluated before use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. Hamann, A.[2021]

Semaglutide 2.4 mg/week, a GLP-1 receptor analogue, has shown promising results in achieving over 15% weight loss in individuals with obesity, marking a significant advancement in obesity treatment options.

The dual agonist tirzepatide, which targets both GLP-1 and glucose-dependent insulinotropic polypeptide, has demonstrated even greater weight loss potential, suggesting that combining different gut hormone mechanisms could enhance the effectiveness of obesity pharmacotherapy compared to existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New therapies for obesity. Papamargaritis, D., le Roux, CW., Holst, JJ., et al.[2022]

GLP-1 receptor agonists, specifically semaglutide, have been shown to significantly promote weight loss in clinical trials, with superior efficacy compared to placebo and other antidiabetic medications.

The STEP trial demonstrated that a higher dose of semaglutide (2.4 mg, once-weekly) specifically targets obesity, leading to its FDA approval as Wegovy for weight management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wegovy (semaglutide): a new weight loss drug for chronic weight management. Singh, G., Krauthamer, M., Bjalme-Evans, M.[2022]

Liraglutide, a GLP-1 receptor agonist, is effective for weight loss in overweight or obese patients, showing greater weight reduction compared to placebo and orlistat, particularly at a dosage of 3 mg daily.

In addition to weight loss, liraglutide has been associated with significant health improvements, including reductions in waist circumference, blood pressure, and better lipid profiles, making it a beneficial option for patients with or without type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Liraglutide, GLP-1 receptor agonist, for chronic weight loss. Moore, KG., Shealy, K., Clements, JN.[2022]

Modest weight loss of 5-10% can lead to significant improvements in cardiovascular health for individuals with obesity, highlighting the importance of even small changes in weight.

Recent FDA approvals of medications like phentermine/topiramate ER, lorcaserin, naltrexone SR/bupropion SR, and liraglutide 3.0 mg provide new pharmacologic options for obesity treatment, which is crucial given the rising obesity epidemic in the USA.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacologic Approaches to Weight Management: Recent Gains and Shortfalls in Combating Obesity. Saunders, KH., Kumar, RB., Igel, LI., et al.[2018]

A comprehensive analysis of the FDA Adverse Event Reporting System revealed 18,675 unique adverse event reports linked to anti-obesity medications (AOMs) among 15,143 patients, highlighting significant safety concerns.

Serious adverse events included a fatality ratio of 4.9%, with cardiovascular complications being particularly prevalent, accounting for 31% of AEs related to phentermine, and indicating a need for ongoing safety monitoring of AOMs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Descriptive analysis of reported adverse events associated with anti-obesity medications using FDA Adverse Event Reporting System (FAERS) databases 2013-2020. Alsuhibani, A., Alrasheed, M., Gari, M., et al.[2022]

In the SURMOUNT-1 trial, tirzepatide significantly reduced the 10-year predicted risk of developing type 2 diabetes (T2D) compared to placebo, with reductions ranging from 12.4% to 14.7% at week 72, depending on the dosage.

Participants with prediabetes experienced greater risk score reductions (16.0%-20.3%) than those without prediabetes (10.1%-11.3%), indicating that tirzepatide is effective across different glycaemic statuses and body mass index levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tirzepatide reduces the predicted risk of developing type 2 diabetes in people with obesity or overweight: Post hoc analysis of the SURMOUNT-1 trial. Hankosky, ER., Wang, H., Neff, LM., et al.[2023]

Long-acting GLP-1 receptor agonists, such as liraglutide and semaglutide, are effective anti-obesity medications that can lead to significant weight loss, with semaglutide showing an average weight loss of 11.6% after one year, compared to 5.5% with liraglutide.

Both medications are generally well tolerated, with similar safety profiles, though they can cause transient gastrointestinal issues; ongoing long-term studies are needed to further evaluate their efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. Christensen, RM., Juhl, CR., Torekov, SS.[2020]

In a Phase II study involving 413 participants with type 2 diabetes, the dual agonist survodutide significantly reduced HbA1c levels and body weight after 16 weeks of treatment, with the most effective doses being 1.8 mg and 2.7 mg once weekly.

Survodutide showed a greater reduction in body weight compared to semaglutide at higher doses, although gastrointestinal side effects were common, affecting 77.8% of participants, suggesting that careful dose escalation may help manage these adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose-response effects on HbA1c and bodyweight reduction of survodutide, a dual glucagon/GLP-1 receptor agonist, compared with placebo and open-label semaglutide in people with type 2 diabetes: a randomised clinical trial. Blüher, M., Rosenstock, J., Hoefler, J., et al.[2023]

Lifestyle modifications are effective in preventing the progression to type 2 diabetes and can be combined with pharmacological treatments for better outcomes.

Among the medications reviewed, phentermine with topiramate showed the greatest weight reduction (10.2 kg), while liraglutide is notable for its long-term efficacy (up to 3 years) in patients with prediabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obesity management among patients with type 2 diabetes and prediabetes: a focus on lifestyle modifications and evidence of antiobesity medications. Nguyen, B., Clements, J.[2019]

Several anti-obesity drugs have been withdrawn from the market due to serious cardiovascular risks, such as fenfluramine and sibutramine, highlighting the importance of safety in obesity treatments.

Current treatments like GLP-1 analogues and metformin not only aid in weight loss but also have favorable cardiovascular profiles, suggesting they could be effective options for managing obesity alongside type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of current and future anti-obesity drugs. Comerma-Steffensen, S., Grann, M., Andersen, CU., et al.[2019]

In two phase I studies involving a total of 149 participants, the dual agonist BI 456906 demonstrated significant weight loss, with a maximum placebo-corrected reduction of 13.8% in body weight observed at week 16 in the multiple rising dose study.

While BI 456906 showed promising efficacy in promoting weight loss, it was associated with an increase in drug-related adverse events, particularly gastrointestinal issues and decreased appetite, leading to discontinuation in some participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I studies of the safety, tolerability, pharmacokinetics and pharmacodynamics of the dual glucagon receptor/glucagon-like peptide-1 receptor agonist BI 456906. Jungnik, A., Arrubla Martinez, J., Plum-Mörschel, L., et al.[2023]

Tirzepatide, administered once weekly, was found to be effective in reducing obesity in individuals with type 2 diabetes, as demonstrated in a large phase 3 trial involving multiple centers.

The study was double-blind and placebo-controlled, ensuring robust results that support tirzepatide as a promising treatment option for weight management in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In adults with BMI ≥27 kg/m2 and type 2 diabetes, adding tirzepatide to a lifestyle intervention increased weight loss at 72 wk. Davidson, MB.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06077864

NCT06077864 | A Study to Test the Effect of Survodutide ... The purpose of this study is to find out whether people with overweight or obesity who take a medicine called survodutide (BI 456906) are less or more likely ...

2. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/metabolic-diseases/obesity/phase-ii-clinical-trial-weight-loss-results

Phase II clinical trial weight loss results Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with survodutide (BI 456906)

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39453356/

Survodutide for the Treatment of Obesity SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk.

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa2401755

A Phase 2 Randomized Trial of Survodutide in MASH and ... Here, we report results from a phase 2 dose-finding trial investigating the efficacy, safety, and side-effect profile of multiple subcutaneous ...

5. jacc.org jacc.org/doi/10.1016/j.jchf.2024.09.004

Survodutide for the Treatment of Obesity: Rationale and ... SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk.

6. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/metabolic-diseases/phase-3-studies-survodutide-obesity-and-overweight

Phase 3 studies survodutide obesity and overweight Data shows nearly 19% weight loss in people with overweight or obesity in Boehringer Ingelheim and Zealand Pharma Phase II trial with ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38330987/

Glucagon and GLP-1 receptor dual agonist survodutide for ... This study aimed to investigate the safety, tolerability, and efficacy of glucagon receptor-GLP-1 receptor dual agonist survodutide (BI 456906) in obesity ...