New Insights on Using Oral Semaglutide versus Dapagliflozin in Patients with Type 2 Diabetes and Metabolic Dysfunction-Associated Steatotic Liver Disease

Background and aims: Increases in both the prevalence and severity of metabolic dysfunction-associated steatotic liver disease (MASLD) and obesity are closely related. Type 2 diabetes (T2DM) has been associated with metabolic dysfunction-associated steatohepatitis (MASH)-related cirrhosis and hepatocellular carcinoma. Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of T2DM and has an important role in weight loss. Also, it may represent a new therapeutic option for the treatment of MASH in obese diabetic patients. The main outcomes were changes from baseline in liver steatosis and fibrosis at week 24.

Material and methods: A total of one hundred eighty-seven patients with T2DM were eligible for this prospective study; ninety-five subjects were treated with oral semaglutide, and ninety-two patients were treated with dapagliflozin as an add-on to metformin. All the subjects were evaluated using Vibration Controlled Transient Elastography (VCTE) from June to December 2022.

Results: From our cohort, 54% of the patients were females, with a mean age of 59.92 ± 11.89 years and a mean body mass index (BMI) of 29.53 ± 5.33 kg/m². Following a six-month medication period, we observed a substantial reduction in anthropometric measurements, including the BMI, waist circumference (WC), and waist-to-hip ratio (WtHr), in both groups. Regarding HbA1c, a notable decrease was observed in the semaglutide group (p < 0.001) when compared to the dapagliflozin group (p = 0.011). In addition, the liver stiffness measurement (LSM) according to VCTE improved significantly in the semaglutide group participants from 8.07 ± 2.90 kPa at baseline to 6.51 ± 3.09 kPa after medication (p < 0.001).

Conclusion: The superior metabolic effects of semaglutide, correlated to dapagliflozin, may contribute to a more efficient decrease in hepatic stress and injury, leading to a substantial enhancement of liver function in T2DM patients. Further investigations conducted over an ideal timeframe are necessary to confirm the evidence presented in this study.