Effect of Erugliflozin On Liver Fat, Liver Fibrosis and Glycemic Control in Type II DM Patients With NASH/NAFLD

Study Overview
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Brief Summary
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Open-label, prospective, single-arm, multicenter study to determine effects of Ertugliflozin on liver fat, liver fibrosis & glycemic control in subjects with Type 2 Diabetes Mellitus (T2DM) with Non-Alcoholic Fatty Liver Disease (NAFLD)/Non-Alcoholic Steatohepatitis (NASH)

Official Title
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Effects of Ertugliflozin on Liver Fat, Liver Fibrosis & Glycemic Control in Subjects With Type 2 Diabetes Mellitus (T2DM) & Non-Alcoholic Fatty Liver Disease /Non-Alcoholic Steatohepatitis

Conditions
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Liver Fat, Liver Fibrosis, Glycemic Control, Body Weight Changes, Waist Circumference, Tolerance

Intervention / Treatment
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* Drug: Ertugliflozin 5 mg, 15mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient able to provide written informed consent Adult males & females between 18 to 65 years SGLT2i and insulin naïve patients BMI >23 Kg/m2 HbA1C % ≥ 6.5 to 10 Documented hepatic steatosis or fatty liver disease on Ultrasound Patient with Type II Diabetes Mellitus Exclusion Criteria: History of use of SGLT 2 inhibitors or Glucagon-like peptide (GLP) 1 agonist or insulin; 3 months prior to enrollment in the study. Pioglitazone use in the past 6 months History of vitamin E use (400mg twice daily) 3 months prior to enrollment in the study. History of anti-obesity medication or weight loss procedure (bariatric surgery) use within 3 months prior to enrollment in the study. History of uncontrolled Endocrine disorder (for example uncontrolled hypothyroidism, or that requires frequent dose adjustment, or Cushing's syndrome) History of liver disease including viral hepatitis, auto-immune hepatitis, liver cirrhosis, hepatocellular carcinoma and/or HIV History of recurrent UTIs and mycotic infection. Severely ill patients (who have high grade fever, sepsis or acute infection) Pregnant woman, lactating woman or planning pregnancy during study duration History of Drug-induced liver disease (e.g. amiodarone, valproate, tamoxifen, methotrexate, steroids (including homeopathic medicines). History of active substance abuse (cannabinoid-derived substances like heroin, cocaine, amphetamines) based on history and/or laboratory tests Alcohol intake 10 - 30 g/day (three drinks per day) within the previous year Active substance abuse such as acetaminophen over-use, hashish, tobacco products, heroin, cocaine or amphetamines. Severe hepatic impairment ( AST & ALT levels > 3 times upper limit normal

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ertugliflozin<br>Ertugliflozin 5/15mg once daily with standard of care | Drug: Ertugliflozin 5 mg, 15mg<br>* Ertugliflozin 5/15mg once daily in addition to standard of care<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiologic liver parameters | Number of participants reported change in liver fat content from baseline, as quantified by fibroscan | up to 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c% levels compare with baseline in 6 months | Efficacy | up to 24 weeks | 
| Change in body weight compare with baseline in 6 months | Body Weight | up to 24 weeks | 
| Change in waist circumference compare with baseline in 6 months | Waist Circumference | up to 24 weeks | 
| Fibrosis 4 score levels compare with baseline in 6 months | Fibrosis Scoring < 1.45 indicates Fibrosis Stage 0-2, 1.45 to 3.25 is deemed indeterminate fibrosis stage, > 3.25 indicates Fibrosis stage 3-4 | up to 24 weeks | 
| Non-Alchoholic Fatty Liver Disease Fibrosis Score levels compare with baseline in 6 months | Non-Alchoholic Fatty Liver Disease Fibrosis Scoring, < -1.455 indicates Fibrosis Stage 0-2, -1.455 to 0.676 is considered indeterminate fibrosis stage, > 0.676 indicates Fibrosis Stage 3-4 | up to 24 weeks | 
| Frequency of adverse events in 6 months | Safety | up to 24 weeks |