What is the mechanism of action of this treatment?

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include Pan-PPAR agonists like Lanifibranor, which target multiple PPAR subtypes to regulate lipid metabolism, inflammation, and insulin sensitivity. This is crucial for NAFLD patients as it addresses key factors contributing to liver disease progression. Additionally, SGLT2 inhibitors improve glycemic control and reduce liver fat by promoting glucose excretion through urine. GLP-1 receptor agonists also enhance insulin sensitivity and decrease liver fat. These treatments are essential as they tackle the metabolic dysfunctions underlying NAFLD.

What side effects are associated with this type of intervention?

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include PPAR agonists like pioglitazone and rosiglitazone, which can cause weight gain, fluid retention, and an increased risk of heart failure. Statins, often used to manage associated dyslipidemia, may lead to muscle pain and liver enzyme abnormalities. GLP-1 receptor agonists, such as liraglutide, can cause gastrointestinal issues like nausea and vomiting. SGLT2 inhibitors, another class of drugs used in combination therapies, may lead to urinary tract infections and genital infections. Lanifibranor, a Pan-PPAR agonist under investigation, may share similar side effects with other PPAR agonists, including potential liver enzyme elevations and cardiovascular risks.

What prior FDA approvals exist?

As of now, there are no FDA-approved drugs specifically for the treatment of Non-alcoholic Fatty Liver Disease (NAFLD). However, several drugs are being studied for their potential benefits in NAFLD, including those targeting metabolic pathways similar to Lanifibranor, a Pan-PPAR agonist. Lanifibranor is being investigated for its effects on glycemic control and liver health in patients with NAFLD and Type 2 Diabetes Mellitus. Other investigational treatments include PPAR agonists like pioglitazone and elafibranor, which have shown promise in clinical trials for improving liver histology and metabolic parameters in NAFLD patients.

What other types of research exist?

Promising novel alternatives to Lanifibranor for NAFLD patients include: 1) GLP-1 receptor agonists (e.g., semaglutide), which have shown efficacy in reducing liver fat and improving liver histology; 2) FXR agonists (e.g., obeticholic acid), which target bile acid pathways to reduce liver inflammation and fibrosis; 3) PPAR agonists (e.g., elafibranor), which target multiple pathways involved in lipid metabolism and inflammation; and 4) FGF21 analogs (e.g., pegbelfermin), which have shown potential in reducing liver fat and improving metabolic parameters.

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PPAR agonist

Lanifibranor + Empagliflozin for Type 2 Diabetes (LEGEND Trial)

Phase 2

Waitlist Available

Research Sponsored by Inventiva Pharma

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up date of randomisation until the end of treatment at week 24

Summary

This trial is testing a new drug called lanifibranor to see if it can help people with Type 2 Diabetes control their blood sugar levels. It also looks at how well lanifibranor works when combined with another drug that helps remove sugar from the body through urine. The goal is to find better ways to manage blood sugar for people who struggle with current treatments.

Who is the study for?

Adults with NASH and Type 2 Diabetes Mellitus, HbA1c between 7.0-10.0%, stable on certain diabetes medications or diet alone can join this trial. Exclusions include recent participation in other trials, severe illnesses, specific medication use affecting glucose tolerance, uncontrolled hypertension, high BMI (>45), liver cirrhosis or cancer, significant alcohol consumption within the last 5 years.

What is being tested?

The study tests lanifibranor's effects on blood sugar control against a placebo and examines if combining it with an SGLT2 inhibitor (Empagliflozin) improves outcomes for diabetic patients with NASH.

What are the potential side effects?

Potential side effects may include typical drug reactions like nausea, headaches or allergic responses; however specific side effects of Lanifibranor and Empagliflozin are not detailed here.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ date of randomisation until the end of treatment at week 24

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~date of randomisation until the end of treatment at week 24

This trial's timeline: 3 weeks for screening, Varies for treatment, and date of randomisation until the end of treatment at week 24 for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Assessment of the effect of lanifibranor alone compared to placebo and the effect of lanifibranor in combination with empagliflozin compared to placebo on absolute change in HbA1c from baseline (Week 0) to Week 24

Side effects data

From 2021 Phase 3 trial • 5988 Patients • NCT03057951

15%

Cardiac failure

Hypotension

Hypertension

Urinary tract infection

Renal impairment

Hyperkalaemia

Fall

Atrial fibrillation

Diabetes mellitus

Hyperuricaemia

Anaemia

Acute kidney injury

Pneumonia

COVID-19

Death

Acute myocardial infarction

Cardiac failure congestive

Basal cell carcinoma

Cardiac failure chronic

Cellulitis

Syncope

Chronic kidney disease

COVID-19 pneumonia

Ischaemic stroke

Coronary artery disease

Chronic obstructive pulmonary disease

Myocardial infarction

Sepsis

Transient ischaemic attack

Angina unstable

Cerebrovascular accident

Angina pectoris

Ventricular tachycardia

100%

80%

60%

40%

20%

Study treatment Arm

Placebo

10 mg Empagliflozin

Trial Design

3Treatment groups

Experimental Treatment

Placebo Group

Group I: Lanifibranor (IVA337) (800 mg/day) plus Empagliflozin (10mg/day)Experimental Treatment2 Interventions

2 Lanifibranor tablets 400 mg plus 1 Empagliflozin tablet 10mg with food --\> once a day (quaque die, QD)

Group II: Lanifibranor (IVA337) (800 mg/day)Experimental Treatment1 Intervention

2 Lanifibranor tablets 400 mg with food --\> once a day (quaque die, QD)

Group III: Matching placeboPlacebo Group1 Intervention

2 Placebo to match tablets with food --\> once a day (quaque die, QD)

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

IVA337

2015

Completed Phase 2

~440

Empagliflozin

2017

Completed Phase 4

~181750

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Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include Pan-PPAR agonists like Lanifibranor, which target multiple PPAR subtypes to regulate lipid metabolism, inflammation, and insulin sensitivity. This is crucial for NAFLD patients as it addresses key factors contributing to liver disease progression. Additionally, SGLT2 inhibitors improve glycemic control and reduce liver fat by promoting glucose excretion through urine. GLP-1 receptor agonists also enhance insulin sensitivity and decrease liver fat. These treatments are essential as they tackle the metabolic dysfunctions underlying NAFLD.