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

Trial Summary

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.

What data supports the effectiveness of the drug BI 456906 for obesity?

Research shows that survodutide (BI 456906), a dual glucagon/GLP-1 receptor agonist, helps reduce body weight in people with type 2 diabetes. Similar drugs like semaglutide, which also target GLP-1 receptors, have been effective in promoting weight loss in people with obesity. ^{1 2 3 4 5}

What safety information is available for BI 456906 (Survodutide) in humans?

There is no specific safety data available for BI 456906 (Survodutide) in the provided research articles. ^{6 7 8 9 10}

What makes the drug BI 456906 unique for treating obesity?

BI 456906, also known as Survodutide, is unique because it is a novel treatment option for obesity that may offer a different mechanism of action compared to existing drugs like orlistat or liraglutide, which are GLP-1 receptor agonists. While specific details about BI 456906's mechanism are not provided, its development suggests it could provide an alternative for patients who do not respond well to current treatments. ^{4 6 11 12 13}

What is the purpose of this trial?

This trial tests a medicine called survodutide, which is injected regularly to help people with obesity or overweight lose weight. It focuses on adults with a high BMI and related health issues who have tried dieting before. The goal is to see if survodutide can reduce serious heart problems and improve overall health.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Germany 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. [2023]

2. England 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. [2023]

3. England pubmed.ncbi.nlm.nih.gov

New therapies for obesity. [2022]

4. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Wegovy (semaglutide): a new weight loss drug for chronic weight management. [2022]

6. United States 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. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Pharmacologic Approaches to Weight Management: Recent Gains and Shortfalls in Combating Obesity. [2018]

8. Netherlands 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. [2022]

9. England 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. [2023]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Benefit-Risk Assessment of Obesity Drugs: Focus on Glucagon-like Peptide-1 Receptor Agonists. [2020]

11. England 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. [2019]

12. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Cardiovascular effects of current and future anti-obesity drugs. [2019]

13. England pubmed.ncbi.nlm.nih.gov

Liraglutide, GLP-1 receptor agonist, for chronic weight loss. [2022]