Dapagliflozin May Reduce Liver Fat in Type 2 Diabetes Independent of Weight Loss: Study
Researchers have found in a secondary analysis of a clinical trial published in Obesity that taking dapagliflozin 10 mg daily for 12 months was associated with a reduction in liver fat among patients with type 2 diabetes. Notably, this benefit appeared to be independent of weight loss and other metabolic improvements. The study was conducted by Anna V. and colleagues.
Hepatic steatosis is a very common finding in patients with type 2 diabetes and is a contributing factor to the increasing incidence of metabolic dysfunction-associated steatotic liver disease. Although SGLT2 inhibitors are widely used for glycemic control and cardiovascular and renal protection, their effect on liver fat content and the mechanisms involved are still being explored.
This is a secondary analysis of a randomized, placebo-controlled clinical trial involving 56 patients with type 2 diabetes. Patients were randomly assigned to receive either placebo or 10 mg of dapagliflozin once daily. Anthropometric parameters, liver MRI-PDFF for the measurement of liver fat, fasting glucose, glycated hemoglobin (HbA1c), and liver function tests were evaluated at baseline and at 12 months.
Key findings
Dapagliflozin caused a significant reduction in liver fat after 12 months of treatment as measured by MRI-PDFF.
The mean change in liver fat fraction was −3.7% in the dapagliflozin group, while it increased by 0.5% in the placebo group (p = 0.001).
Body weight was reduced by −3.84 kg in the dapagliflozin group compared with −1.42 kg in the placebo group, giving a statistically significant difference (p = 0.015).
Glycemic parameters were also improved, with HbA1c levels decreasing by −0.52% in the dapagliflozin group compared with an increase of 0.11% in the placebo group (p = 0.012).
Dapagliflozin caused a reduction in both body weight and liver fat; however, the indirect effect of weight reduction on the change in liver fat was not statistically significant.
Twelve months of treatment with dapagliflozin in patients with type 2 diabetes led to a significant reduction in liver fat as measured by MRI-PDFF compared with placebo, and this was achieved independently of weight loss and other metabolic changes. These results indicate that SGLT2 inhibition may have direct effects on the liver that are independent of glycemic and weight-related effects, and this has important implications for the high prevalence of hepatic steatosis in patients with type 2 diabetes.
Reference:
Naumova, A. V., Cunha, G. M., Kim, N. J., Lu, J., Isquith, D., Chu, B., Maynard, C., Mahdavi, A., Firoozeh, N., Ordovas, K., Zhao, X.-Q., & Kim, F. (2026). Dapagliflozin-associated reduction in liver fat is independent of weight loss in patients with type 2 diabetes. Obesity (Silver Spring, Md.), oby.70134. https://doi.org/10.1002/oby.70134
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