Obeticholic Acid and Insulin Sensitivity in Overweight Patients with Prediabetes

BACKGROUND. Due to its role as a risk factor for the emergence of metabolic illnesses including type 2 diabetes, cardiovascular disease, and certain cancers with pandemic evolution, obesity is a serious public health concern. Diabetes mellitus type 2 (T2DM) poses a major risk to human health. The byproducts of the breakdown of cholesterol are bile acids, which are crucial for preserving cholesterol homeostasis. Research indicates that bile acids might control insulin sensitivity, energy metabolism, and glucose tolerance. Farnesoid X receptors (FXRs) are crucial for controlling bile acid production and hepatic glucose metabolism. The ligand for FXR The semisynthetic derivative of chenodeoxycholic acid, a bile acid, is obeticholic acid (OCA). Research indicates that bile acids may be a viable therapeutic target for type 2 diabetes (T2DM) given that therapy with oleic acid (OCA) enhanced insulin sensitivity and decreased indicators of liver inflammation and fibrosis in individuals with T2DM and nonalcoholic steatohepatitis (NASH).

AIM. To assess Obeticholic acid’s effectiveness in obese individuals with prediabetes.

MATERIALS AND METHODS. Over the course of three months, we performed a randomized single blind placebo controlled trial on eighty-two overweight and obese patients with prediabetes in the outpatient clinic at Ain Shams University Hospital. Through block randomization, patients were split into two groups (Group A received daily oral tablets containing 5 mg of obeticholic acid, while Group B received non-sweet capsules as a placebo). Three follow-up visits were conducted to ensure adherence and monitor for any emergence of side effects.

RESULTS. 82 patients of matched age and sex criteria who underwent block randomization into 2 equal groups, group (A) representing cases and group (B) the placebo controlled group, with 3 months’ regular follow up showed at end of treatment statistically significant difference in weight being lower in group (A) with p-value 0.004 with decreased parameters of glycemic profile (Fasting insulin, FPG, HOMA_IR, 2h PP, HbA_1c) in group (A) with p-value <0.001 except 2hpp which p-value is 0.006. Also ALT was much decreased in group (A) with p-value <0.001. Lipid profile didn’t show significant difference between 2 groups except for TGs which deceased in follow up in group (A) with p-value <0. 001. Additionally, it should be highlighted that there was no statistically significant difference between the control group’s baseline and post-treatment data.

CONCLUSION. In individuals who are overweight or obese and have insulin resistance and prediabetes, activation of FXR by OCA results in enhanced insulin sensitivity. Patients who received OCA also lost weight.

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