BI 456906 for Obesity

(SYNCHRONIZE™-1 Trial)

Recruiting at 128 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: Obesity medications, Glucose-lowering agents

Disqualifiers: Type 2 diabetes, Heart failure, 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: 17

Duration: 76 weeks

727 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is open to adults who are at least 18 years old and have * a body mass index (BMI) of 30 kg/m² or more, or * a BMI of 27 kg/m² or more and at least one health problem related to their weight. People with type 2 diabetes cannot take part in this study. Only people who have previously not managed to lose weight by changing their diet can participate. The purpose of this study is to find out whether a medicine called survodutide (BI 456906) helps people living with overweight or obesity to lose weight. Participants are divided into 3 groups by chance, like drawing names from a hat. 2 groups get different doses of survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Every participant has a 2 in 3 chance of getting survodutide. Participants inject survodutide or placebo under their skin once a week for about one and a half years. In addition to the study medicine, all participants receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for about 1 year and 7 months. During this time, it is planned that participants visit the study site up to 14 times and receive 6 phone calls by the site staff. The doctors check participants' health and take note of any unwanted effects. The participants' body weight is regularly measured. The results are compared between the groups to see whether the treatment works.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are taking medication for obesity, you must stop at least 3 months before joining the study.

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}

Is BI 456906 (Survodutide) safe for humans?

There is no specific safety data available for BI 456906 (Survodutide) in the provided research articles. However, similar drugs like liraglutide and semaglutide, which are glucagon-like peptide-1 receptor agonists, are generally well tolerated with common side effects being temporary stomach issues. Long-term safety monitoring is recommended for these types of medications. ^{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 glucagon-like peptide-1 (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. ^{3 9 11 12 13}

Eligibility Criteria

This trial is for adults over 18 without diabetes, with a BMI of at least 30 kg/m² or a BMI of 27 kg/m² plus weight-related health issues. Candidates should have tried and failed to lose weight through dieting before.

Inclusion Criteria

I have obstructive sleep apnea.

My condition meets other specific criteria not listed.

I have high blood pressure.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive survodutide or placebo injections weekly and counseling for diet and exercise

76 weeks

14 visits (in-person), 6 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• BI 456906

Trial Overview The study tests survodutide (BI 456906) on people with obesity, comparing two different doses against a placebo. Participants will self-inject weekly for around one and a half years while also receiving lifestyle 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]

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]

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]

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]

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. Germany pubmed.ncbi.nlm.nih.gov

[Pharmacotherapy of obesity]. [2021]

4. England pubmed.ncbi.nlm.nih.gov

New therapies for obesity. [2022]

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

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

6. 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]

7. 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]

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

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

9. 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]

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

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

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]