Endocrinol Metab.  2018 Sep;33(3):387-394. 10.3803/EnM.2018.33.3.387.

Effect of Dapagliflozin on Alanine Aminotransferase Improvement in Type 2 Diabetes Mellitus with Non-alcoholic Fatty Liver Disease

• Choi DH
• Jung CH
• Mok JO
• Kim CH
• Kang SK
• Kim BY

• KMID: 2447029
• DOI: http://doi.org/10.3803/EnM.2018.33.3.387

Abstract

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.

Keyword

Sodium-glucose cotransporter-2 inhibitor; Diabetes mellitus, type 2; Non-alcoholic fatty liver disease

MeSH Terms

Alanine Transaminase*
Alanine*
Body Weight
Confounding Factors (Epidemiology)
Diabetes Mellitus, Type 2*
Humans
Hypoglycemic Agents
Liver
Metformin
Non-alcoholic Fatty Liver Disease*
Weight Loss
Alanine
Alanine Transaminase
Hypoglycemic Agents
Metformin

Figure

• 

  Fig. 1 Flow diagram for selection of study participants. T2DM, type 2 diabetes mellitus; NAFLD, non-alcoholic fatty liver disease; OAD, oral antidiabetic drugs; DPP4i, dipeptidyl peptidase-4 inhibitor.

• 

  Fig. 2 Comparison of alanine aminotransferase (ALT) reduction between two groups. ALT decreased significantly in both groups but decreased more in the dapagliflozin group than in the dipeptidyl peptidase-4 (DPP4) inhibitor group. The difference in the ALT reduction between the two groups was statistically significant (−21.1 U/L vs. −9.5 U/L, P=0.008).

• 

  Fig. 3 The proportion of patients with alanine aminotransferase (ALT) normalization. The percentage of ALT normalization was significantly higher in the dapagliflozin group than in the dipeptidyl peptidase-4 (DPP4) inhibitor group (80.0% vs. 61.5%, P=0.041).

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