Ursodeoxycholic Acid as add-on Therapy in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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Diabetes mellitus (DM) is a complex metabolic disorder characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It is one of the most prevalent metabolic disorders globally. Despite the advancement in anti-diabetic drug therapy, most patients fail to achieve optimal glycemic control. therefore, there is a large unmet need to develop new strategies to improve the therapeutic outcomes in diabetic patients. This study is designed to evaluate the efficacy of ursodeoxycholic acid as adjunctive therapy in patients with type 2 diabetes mellitus.

Detailed Description
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Diabetes mellitus (DM) is a complex metabolic disorder characterized by hyperglycemia and abnormalities in carbohydrate, fat, and protein metabolism. It is one of the most prevalent metabolic disorders globally. More than 75% of diabetic patients live in low- and middle-income countries. About 90% of diabetic patients have type 2 diabetes. Insulin resistance (IR) and β-cell dysfunction are the two main pathophysiological events contributing to type 2 diabetes. Insulin resistance is a pathological condition in which insulin-dependent tissues fail to properly respond to normal circulatory levels of insulin. Inflammatory mediators play a key role in insulin resistance. For example, tumor necrosis factor alpha (TNF-α) impairs insulin signaling via serine phosphorylation of insulin receptor substrate (IRS-1). Additionally, it reduces glucose transporter-4 (GLUT-4) expression, limiting glucose entry into adipocytes and skeletal muscle cells. Similarly, IL-6 induces IRS degradation. Oxidative stress interferes with insulin signal transduction leading to IR. It activates several serine-threonine kinase pathways, which, in turn, phosphorylates IRS proteins leading to subsequent degradation. β-cell dysfunction is associated with β-cell death. In an excessive nutritional state, as in obesity, hyperglycemia and hyperlipidemia are often present, favoring IR and chronic inflammation. Under these circumstances, β-cells are subject to toxic pressures including inflammation, endoplasmic reticulum stress, oxidative stress, as well as amyloid stress, that ultimately lead to loss of islet integrity. Ursodeoxycholic acid (UDCA) is an endogenous hydrophilic bile acid normally present in human bile and traditionally used for the treatment of liver diseases. UDCA has direct antioxidant properties. It decreased glucose levels, alleviated hyperinsulinemia, and improved islet function in rats with liver fibrosis. Therefore, this study is designed to evaluate the efficacy of ursodeoxycholic acid as adjunctive therapy in patients with type 2 diabetes mellitus.

Official Title
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A Clinical Study Evaluating the Use od Ursodeoxycholic Acid as Adjuvant Therapy in Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Ursodeoxycholic acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who have been diagnosed with type 2 diabetes mellitus within the previous 12 months. Glycated hemoglobin (HbA1c) between 7% and 9%. Body mass index ≥ 25 kg/m2 Exclusion Criteria: Pregnant or nursing women. Type 1 diabetes mellitus. Liver disease (alanine aminotransferase > 3 upper normal limit). Kidney disease (estimated glomerular filtration rate < 60 ml/min/1.73 m2). Inflammatory bowel diseases History of allergy and/or adverse reactions to the drugs used in the study.

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Group 1<br>44 diabetic patients receiving dual treatment with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors (such as vildagliptin) | |
| Active Comparator: Group 2<br>44 diabetic patients who will receive ursodeoxycholic acid 500 mg orally twice daily in addition to dual treatment with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors (such as vildagliptin) | Drug: Ursodeoxycholic acid<br>* ursodeoxycholic acid 500 mg orally twice daily for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic control | Fasting blood glucose, glycated hemoglobin | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid profile | Total cholesterol, triglycerides, HDL-cholesterol, and LDL-cholesterol | 12 weeks | 
| Insulin resistance | Fasting insulin, HOMA-IR | 12 weeks | 
| Oxidative stress marker | Serum malondialdehyde | 12 weeks | 
| Inflammation marker | Interleukin-6, high mobility group box-1 | 12 weeks | 
| Serum asprosin |  | 12 weeks |