Survodutide for Obesity and Fatty Liver Disease

Recruiting at 49 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

218 Participants Needed

Trial Summary

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.

What data supports the idea that Survodutide for Obesity and Fatty Liver Disease is an effective treatment?

The available research does not provide specific data on Survodutide for Obesity and Fatty Liver Disease. However, it mentions other treatments like cotadutide, which showed improvements in liver fat and metabolic health in people with obesity and type 2 diabetes. This suggests that similar drugs targeting the same pathways might be effective. Without direct data on Survodutide, we can't confirm its effectiveness, but the success of similar treatments offers some hope. ^{1 2 3 4 5}

What data supports the effectiveness of the drug Survodutide for obesity and fatty liver disease?

Research on similar drugs, like cotadutide, which also targets glucagon-like peptide 1 and glucagon receptors, shows that it can reduce liver fat and improve liver health in people with obesity and type 2 diabetes. This suggests that Survodutide, which may have similar mechanisms, could also be effective for these conditions. ^{1 2 3 4 5}

What safety data is available for Survodutide (BI 456906) in treating obesity and fatty liver disease?

The provided research does not contain specific safety data for Survodutide (BI 456906) or its other names. The studies mentioned focus on other treatments like DA-3091, liraglutide, saroglitazar, and cotadutide, which are not directly related to Survodutide. Therefore, no relevant safety data for Survodutide is available in the given research. ^{4 5 6 7 8}

Is Survodutide a promising drug for obesity and fatty liver disease?

Yes, Survodutide is a promising drug for obesity and fatty liver disease because it is similar to other treatments that have shown positive effects in reducing liver fat and improving liver health. These treatments also help with weight loss and managing diabetes, which are important for treating these conditions. ^{2 6 9 10 11}

What makes the drug Survodutide unique for treating obesity and fatty liver disease?

Survodutide is unique because it is a dual agonist, meaning it targets two different pathways in the body, which may enhance its effectiveness in treating obesity and fatty liver disease compared to other treatments that typically target a single pathway. ^{2 6 9 10 11}

What is the purpose of this trial?

This study is open to adults who are at least 18 years old and have * presumed or confirmed NASH together with overweight or obesity and * a body mass index (BMI) of 30 kg/m² or more, or * a BMI of 27 kg/m² and at least one weight-related health problem. People with a history of other chronic liver diseases cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people living with obesity or overweight and a confirmed or presumed liver disease called nonalcoholic steatohepatitis (NASH) to have less liver fat and to lose weight. Participants are put into 2 groups randomly, which means by chance. 1 group gets 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 and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week for about 1 year. 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 3 months. During this time, it is planned that participants visit the study site up to 14 times and receive 3 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. At 3 of the visits, the participants' liver is measured using different imaging methods. The results are compared between the groups to see whether the treatment works.

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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 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 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]

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 PPAR&#947; 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]

References

1. Japan 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. [2023]

2. United States 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. [2022]

3. Netherlands 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. [2023]

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

Cotadutide promotes glycogenolysis in people with overweight or obesity diagnosed with type 2 diabetes. [2023]

5. France 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. [2023]

6. Germany 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. [2018]

7. China 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]. [2018]

8. Switzerland 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. [2023]

9. Netherlands 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. [2022]

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

Deuterium-Stabilized (R)-Pioglitazone (PXL065) Is Responsible for Pioglitazone Efficacy in NASH yet Exhibits Little to No PPAR&#947; Activity. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Cotadutide effect in liver and adipose tissue in obese mice. [2023]