Survodutide for Obesity and Fatty Liver Disease

No longer recruiting at 60 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: Liver injury drugs

Disqualifiers: Chronic liver diseases, Cirrhosis, 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: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a medicine called survodutide can help individuals with obesity or overweight and nonalcoholic steatohepatitis (NASH) reduce liver fat and lose weight. Participants are divided into two groups: one receives survodutide, while the other receives a placebo (a substance with no active medicine) for comparison. Eligible participants should have a body mass index (BMI) of 30 or more, or a BMI of 27 with a weight-related health issue such as type 2 diabetes or high blood pressure. Participants will inject the study treatment under their skin weekly for about a year, with regular check-ups to monitor their health. 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.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop your current medications. However, you cannot participate if you are taking medications associated with liver injury, hepatic steatosis, or steatohepatitis.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that you cannot take part if you are on medications associated with liver injury or certain liver conditions. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that survodutide is likely to be safe for humans?

Research has shown that survodutide, the treatment under study, has undergone previous testing. In an earlier study, most patients experienced improvement in liver disease related to MASH, a condition similar to NASH, suggesting that survodutide might aid liver issues. Another study found that patients taking survodutide lost a significant amount of weight, offering hope for those dealing with obesity.

Regarding safety, studies demonstrated that survodutide is generally well-tolerated, with most participants not experiencing serious side effects. Some individuals did encounter side effects, but these were not severe enough to halt further testing. The current study's later phase indicates that survodutide has passed earlier safety tests and is deemed safe for larger groups.

Overall, while minor side effects may occur, research so far supports that survodutide is safe for participation in clinical trials. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Survodutide is unique because it targets obesity and fatty liver disease by combining two mechanisms into one treatment. Unlike current standard options that often focus separately on weight loss or liver health, survodutide is designed to address both issues simultaneously. This dual-action approach could potentially offer more comprehensive benefits, making it an exciting development for researchers looking to improve outcomes for individuals with these conditions.

What evidence suggests that survodutide might be an effective treatment for obesity and fatty liver disease?

Research shows that survodutide, the investigational treatment in this trial, can help people with NASH (a liver condition) and obesity. In earlier studies, up to 87% of people taking survodutide experienced a significant reduction in liver fat, compared to just 19.7% of those taking a placebo (a pill with no active medicine). Additionally, 83% of participants showed major improvements in liver fibrosis, a type of liver damage. Survodutide has also helped people with type 2 diabetes lose weight and lower their blood sugar levels. These findings suggest that survodutide may reduce liver fat and support weight loss for those with NASH and obesity. Participants in this trial will receive either survodutide or a placebo to further evaluate these effects. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

Adults over 18 with obesity or overweight and presumed or confirmed NASH can join. They must have a BMI of at least 30, or a BMI of 27 plus a weight-related health issue like hypertension, type 2 diabetes, dyslipidemia, sleep apnea, or cardiovascular disease. Those with other chronic liver diseases are excluded.

Inclusion Criteria

My BMI is over 30, or it's over 27 with a condition like high blood pressure or diabetes.

Exclusion Criteria

I am not taking medication known to harm the liver.

I have been diagnosed with cirrhosis.

Evidence of portal hypertension

Timeline for a Trial Participant

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 once a week for about 1 year, with regular health checks and counseling for diet and exercise

48 weeks

14 visits (in-person), 3 phone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment, including liver imaging and weight measurements

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Survodutide

Trial Overview

The trial tests if Survodutide reduces liver fat and aids weight loss in people with NASH and obesity/overweight. Participants are randomly assigned to receive either Survodutide doses or placebo weekly for about a year while also getting diet and exercise counseling.

How Is the Trial Designed?

Group I: Treatment arm Experimental Treatment 1 Intervention

Group II: Placebo arm 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

In an 8-week study with obese mice, the new sustained-release formulation of exenatide, DA-3091, significantly reduced body weight gain more effectively than the obesity drug sibutramine, indicating its potential as a weight management treatment.

DA-3091 also showed promise in treating non-alcoholic fatty liver disease (NAFLD) by significantly lowering liver injury markers (ALT and AST) and reducing hepatic lipid accumulation in mice, suggesting its efficacy in addressing metabolic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a new sustained-release microsphere formulation of exenatide, DA-3091, on obese and non-alcoholic fatty liver disease mice. Son, JP., Son, MK., Jun, SW., et al.[2018]

Liraglutide treatment in ApoE knockout mice on a high-fat diet significantly reduced body weight, fasting plasma glucose, triglycerides, total cholesterol, and liver enzyme levels, indicating its efficacy in preventing nonalcoholic fatty liver disease (NAFLD).

The mechanism of liraglutide's protective effects involves increasing Acrp30 levels and enhancing AMPK phosphorylation, which helps reduce hepatic lipid accumulation and metabolic disturbances associated with a high-fat diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Liraglutide protects against nonalcoholic fatty liver disease in ApoE knockout mice with high-fat diet and silenced Acrp30 by increasing AMPK]. Zhao, XY., Zhang, LL., Suolang, QZ., et al.[2018]

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Samajdar, SS., Das, S.[2023]

In a phase 2a trial involving men and women with overweight or obesity and type 2 diabetes, cotadutide significantly reduced liver glycogen and fat compared to both placebo and liraglutide, indicating its efficacy in improving liver health.

The safety and tolerability of cotadutide were found to be comparable to previous studies, suggesting it is a safe option for treating conditions like non-alcoholic steatohepatitis and type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. Parker, VER., Robertson, D., Erazo-Tapia, E., et al.[2023]

In a phase I study involving 37 participants with varying degrees of renal impairment, cotadutide showed similar pharmacokinetics across all renal function groups, indicating that its absorption and concentration in the body are not significantly affected by kidney function.

The safety profile of cotadutide was favorable, with most treatment-emergent adverse events being mild to moderate, suggesting that dose adjustments may not be necessary for individuals with renal impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study. Klein, G., Petrone, M., Yang, Y., et al.[2023]

A systematic review of 25 trials involving 2597 adults found that PPAR agonists and GLP-1R agonists significantly improved liver histology in patients with non-alcoholic fatty liver disease (NAFLD), indicating their potential as effective treatments.

SGLT2 inhibitors were shown to reduce liver fat content, further supporting their role in managing NAFLD, especially in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. Mantovani, A., Byrne, CD., Targher, G.[2022]

GLP-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 (SGLT-2) inhibitors are associated with a lower risk of developing nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes, with SGLT-2 inhibitors showing a more significant reduction in incidence (HR 0.78).

Both GLP-1 RA and SGLT-2 inhibitors also reduce the risk of elevated liver enzymes, indicating potential protective effects on liver health in diabetic patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-Like Peptide 1 Receptor Agonists and Sodium-Glucose Cotransporter 2 Inhibitors and Risk of Nonalcoholic Fatty Liver Disease Among Patients With Type 2 Diabetes. Pradhan, R., Yin, H., Yu, O., et al.[2022]

PXL065, a deuterium-stabilized form of the (R)-pioglitazone stereoisomer, retains the efficacy of pioglitazone in treating nonalcoholic steatohepatitis (NASH) while showing limited to no side effects related to weight gain and edema, which are common with the original drug.

In a phase 1a clinical study, PXL065 demonstrated safety and tolerability at doses lower than those of pioglitazone, suggesting it could provide similar or greater efficacy for NASH without the adverse effects associated with PPARγ activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Deuterium-Stabilized (R)-Pioglitazone (PXL065) Is Responsible for Pioglitazone Efficacy in NASH yet Exhibits Little to No PPARγ Activity. Jacques, V., Bolze, S., Hallakou-Bozec, S., et al.[2023]

In a study involving diet-induced obese mice treated with cotadutide for 4 weeks, the drug effectively controlled weight gain, improved glucose intolerance, and reduced insulin resistance, indicating its potential as a treatment for obesity and type 2 diabetes.

Cotadutide also showed significant benefits for liver health by reducing fat accumulation, inflammation, and endoplasmic reticulum stress, while enhancing lipid metabolism, suggesting it could be a promising new therapy for nonalcoholic fatty liver disease (NAFLD) and related metabolic disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cotadutide effect in liver and adipose tissue in obese mice. Marcondes-de-Castro, IA., Oliveira, TF., Spezani, R., et al.[2023]

In a study of 85 patients with type 2 diabetes and non-alcoholic fatty liver disease, liraglutide and metformin were found to significantly reduce body fat mass and promote weight loss over 24 weeks, while gliclazide showed no significant changes in weight or fat mass.

Both liraglutide and metformin improved blood glucose control and liver function markers more effectively than gliclazide, indicating they may be better treatment options for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial. Feng, WH., Bi, Y., Li, P., et al.[2023]

In a phase IIa study involving 145 participants with non-alcoholic fatty liver disease (NAFLD), efinopegdutide (10 mg weekly) resulted in a significantly greater reduction in liver fat content (LFC) compared to semaglutide (1 mg weekly), with reductions of 72.7% and 42.3% respectively after 24 weeks (p < 0.001).

Both treatments led to weight loss, with efinopegdutide showing an 8.5% reduction compared to 7.1% for semaglutide, although efinopegdutide was associated with slightly higher gastrointestinal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. Romero-Gómez, M., Lawitz, E., Shankar, RR., et al.[2023]

Citations

1.

boehringer-ingelheim.com

boehringer-ingelheim.com/human-health/metabolic-diseases/survodutide-top-line-results-mash-fibrosis

survodutide top-line results MASH fibrosis

Survodutide Phase II trial shows 83% of adults treated achieved groundbreaking results in liver disease due to MASH, with significant improvements in fibrosis.

2.

nejm.org

nejm.org/doi/full/10.1056/NEJMoa2401755

A Phase 2 Randomized Trial of Survodutide in MASH and ...

A decrease in liver fat content by at least 30% occurred in 63% of the participants in the survodutide 2.4-mg group, 67% of those in the 4.8-mg ...

3.

boehringer-ingelheim.com

boehringer-ingelheim.com/human-health/metabolic-diseases/breakthrough-phase-2-survodutide-data-liver-fibrosis-mash

Breakthrough Phase 2 survodutide data liver fibrosis MASH

Actual treatment results showed that up to 87.0% of adults achieved at least a 30% relative reduction in liver fat versus 19.7% with placebo, as ...

4.

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 to ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10844353/

a randomised clinical trial - PMC - PubMed Central

Survodutide reduced HbA 1c levels and bodyweight after 16 weeks' treatment in participants with type 2 diabetes.

6.

jacc.org

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

Survodutide for the Treatment of Obesity: Rationale and ...

In a recent phase 2 dose-finding trial, treatment with survodutide resulted in up to a mean 14.9% weight loss over 46 weeks in patients with a ...