Efficacy Study of Diacerein on Glycemic Control and Liver Fat in Type 2 Diabetes Subjects (DGCLFT2DM)

Universidade Federal do Rio de Janeiro

Status and phase: Completed; Phase 3

Conditions: Non-alcoholic Fatty Liver Disease; Diabetes Mellitus, Type 2

Treatments: Drug: Diacerein; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02242149

30194914.3.0000.5257

Details and patient eligibility

About

This study is conducted to test the hypothesis that in uncontrolled type 2 diabetic adults treatment with diacerein will improve glycemic control and will reduce liver fat within a 24 month period.

Full description

Background: Recently, knowledge about diacerhein, an anthraquinone drug with powerful anti-inflammatory properties, revealed that this drug improves insulin sensitivity, mediated by the reversal of chronic subclinical inflammation. Amongst the numerous pathogenetic factors, oxidative stress and apoptosis of hepatocytes initiate many inflammatory processes and are involved in the progression of Non alcoholic fatty liver disease.

Aims:The aim is to evaluate the effect of treatment with diacerein in improvement of glycemic parameters (mean glycated hemoglobin, fasting blood sugar) and reduction of liver fat fraction.

Methods:Two-hundred patients will be randomly allocated either to treatment with diacerein plus their usual therapeutic regimen or to placebo for 24 months. Clinic, laboratory evaluation (including glycated hemoglobin, fasting blood sugar, creatinine, ferritin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), g-glutamyl transpeptidase, alkaline phosphatase, bilirubin, albumin, prothrombin time, platelet count, total cholesterol, high-density and low-density lipoprotein cholesterol and triglycerides and urinary albumin excretion rate no 24-hour urine collection) will be performed before and every 3 months until the end of study. Pro-Inflammatory cytokines, adiponectin and cytokeratin-18 were measured before, at 12 months and at the end of study. Liver fat fraction measurement using controlled attenuation parameter (CAP) by transient elastography. (Fibroscan) will be performed before and after the 12 and 24-month treatment, with the observers blinded to the allocation group.

Enrollment: 84 patients

Sex: All

Ages: 30 to 75 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Type 2 diabetes.
• Presence of liver steatosis diagnosed by ultrasound or transient elastography (Fibroscan®)
• Age 30-75 years.
• HbA1c 7.5- 9.5 for at least 8 weeks prior to screening.
• Stable diabetes therapeutic regimen consisting of either diet, oral hypoglycemic agents with or without insulin for 8 weeks prior to randomization.

Exclusion criteria

• Body mass index > 40 kg/m2
• Serum creatinine ≥180mmol/L or estimated glomerular filtration rate < 30 ml/min.
• Presence of any serious concomitant disease, such as a pulmonary disease or malignant disorders.
• Current daily alcohol ingestion ≥20 g.
• Hepatotoxic drugs.
• Presence of other chronic liver disease other than nonalcoholic fatty liver disease, including hepatitis B virus and hepatitis C virus infection, hemochromatosis, Wilson's disease, alfa-1 antitrypsin deficiency, autoimmune hepatitis.
• Women seeking pregnancy.
• Current use or previous use within 6 months of vitamin E or pioglitazone

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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84 participants in 2 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

All subjects will be given placebo identically matched with regard to shape, color and taste. They will be given one tablet/day for 2 weeks and then two tablets/day for the duration of sudy.

Treatment:

Drug: Placebo

Diacerein

Experimental group

Description:

All subjects will be given diacerein with a starting dose of 50 mg in one tablet once daily for 2 weeks. After 2 weeks, they will be given diacerein 50 mg in one tablet twice daily for the duration of sudy.

Treatment:

Drug: Diacerein