Endocrinology and Metabolism

Dug-Hyun Choi (Choi DH)

1 Article

Clinical Study
Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease: Dug-Hyun Choi, Chan-Hee Jung, Ji-Oh Mok, Chul-Hee Kim, Sung-Koo Kang, Bo-Yeon Kim; Endocrinol Metab. 2018;33(3):387-394. Published online September 18, 2018; DOI: https://doi.org/10.3803/EnM.2018.33.3.387

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Background

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are expected to improve the liver function of patients with non-alcoholic fatty liver disease (NAFLD) combined type 2 diabetes mellitus (T2DM) by its characteristic mechanism. This study was designed to investigate the effect of dapagliflozin, one of the SGLT2i, on the liver function of T2DM with NAFLD when combined with metformin.

Methods

Among patients who received dual oral hypoglycemic agents within the 3 months of diagnosing NAFLD, patients who had abnormal alanine aminotransferase (ALT) level (>40 IU/L) were included. Patients were divided into two groups: metformin+dapagliflozin group and metformin+dipeptidyl peptidase-4 inhibitors (DPP4i) group. Demographic data, biochemical data and the clinical and treatment histories of all patients were reviewed.

Results

A total of 102 patients were included (dapagliflozin group, n=50; DPP4i group, n=52). Dapagliflozin group showed more weight loss and more ALT decline than DPP4i group (−2.9 kg vs. −0.4 kg, P=0.005; −21.1 U/L vs. −9.5 U/L, P=0.008, respectively) and the proportion of patients with ALT normalization after treatment was also significantly higher in the dapagliflozin group (80.0% vs. 61.5%, P=0.041). The effect of dapagliflozin with metformin on ALT normalization remained significant after adjustment for confounding variables including body weight loss (odds ratio, 3.489; P=0.046).

Conclusion

ALT improvement was statistically significant in the dapagliflozin than the DPP4i when combined with metformin and the result was consistent after adjustment for confounding variables including body weight loss.

Citations

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Frontiers in Pharmacology.2022;[Epub] CrossRef
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The Effects of Hypoglycemic Agents on Non-alcoholic Fatty Liver Disease: Focused on Sodium-Glucose Cotransporter 2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists
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Journal of Obesity & Metabolic Syndrome.2019; 28(1): 18. CrossRef
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Molecular and Cellular Endocrinology.2019; 498: 110539. CrossRef
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Diabetes & Metabolism.2019; 45(3): 213. CrossRef

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