Combined Active Treatment in Type 2 Diabetes with NASH (COMBAT_T2_NASH)

German Diabetes Center

Status and phase: Active, not recruiting; Phase 4

Conditions: Non-alcoholic Steatohepatitis (NASH); Type 2 Diabetes; Non-alcoholic Fatty Liver Disease (NAFLD)

Treatments: Drug: Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector; Drug: Placebo matching empagliflozin and placebo pen injector matching semaglutide; Drug: Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT04639414

Combat_T2_NASH_002

2019-001987-31 (EudraCT Number)

Details and patient eligibility

About

The aim of this multicentre, prospective, placebo-controlled, double-blind, randomized, 3-arm parallel group, interventional study is to assess for the first time the effects of either a combined therapy with the antihyperglycemic drugs semaglutide and empagliflozin or empagliflozin monotherapy compared to placebo as potential treatments for non-alcoholic steatohepatitis (NASH) in patients with type 2 diabetes.

Full description

Obesity and type 2 diabetes (T2D) are tightly associated with non-alcoholic fatty liver disease (NAFLD), which in turn predicts the development of T2D and cardiovascular disease.

Up to 80% of NAFLD patients with T2D have NASH and the presence of T2D is an independent risk factor for more-advanced fibrosis, higher rate of fibrosis progression, and increased mortality. Liver-related mortality is increased 10-fold in NASH patients compared with the general population. In addition, people with NASH are at an excessive risk of cardiovascular morbidity and mortality.

Currently, there are no established pharmacotherapies for NASH patients with T2D.

The aim of this trial is to evaluate efficacy of a combined treatment with semaglutide 1 mg/week (GLP1RA) and empagliflozin 10 mg/d (SGLT2I) or ii) empagliflozin 10 mg/d monotherapy by means of histological resolution of NASH in T2D patients without progression of fibrosis after 48 weeks treatment.

To confirm a histological diagnosis of NASH and proof efficacy of treatment, a liver biopsy will be performed prior to screening as well as at the end of treatment phase.

Enrollment: 192 estimated patients

Sex: All

Ages: 25 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of T2D and NASH with fibrosis stage F1-F3
• Age between 25 and 75 years
• HbA1c ≤ 9.5%
• obtained written informed consent

Exclusion criteria

• Contraindications on liver biopsy
• Evidence of cirrhosis on liver biopsy
• Liver disease of other etiology including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis, or liver cirrhosis of any etiology
• History of ketoacidosis
• Alcohol consumption >30 g/d for males and >20 g/d for females
• Past (≥5 years) or current history of alcohol or drug abuse and/or psychiatric disease including severe depression necessitating pharmacological treatment
• Medications that may induce steatosis:tamoxifen, raloxifene, oral glucocorticoids or chloroquine
• Planned pregnancy, pregnant or lactating women, positive pregnancy test, and woman of childbearing potential not using two adequate methods of contraception, including a barrier method and a highly efficacious non-barrier method

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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192 participants in 3 patient groups, including a placebo group

Combined treatment with Empagliflozin and Semaglutide

Experimental group

Description:

Combined treatment with Empagliflozin, film-coated tablet, 10mg once daily and Semaglutide, colourless solution in pre-filled pen, 1mg once weekly

Treatment:

Drug: Empagliflozin 10mg oral tablet / Semaglutide 1mg pen injector

Empagliflozin monotherapy

Experimental group

Description:

Empagliflozin, film-coated tablet, 10mg once daily and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)

Treatment:

Drug: Empagliflozin 10mg oral tablet and placebo pen injector matching semaglutide

Placebo

Placebo Comparator group

Description:

Placebo matching Empagliflozin (film-coated tablet, once daily) and Placebo matching Semaglutide (colourless solution in pre-filled pen, once weekly)

Treatment:

Drug: Placebo matching empagliflozin and placebo pen injector matching semaglutide