7808 Effect of Oral Semaglutide on Hepatic Steatosis and Fibrosis, and Bone Microarchitecture in Non-alcoholic Fatty Liver Disease Complicating Type 2 Diabetes Mellitus: A Prospective, Interventional, Open-Label, Paired Study
Authors: Das L , Bhadada S K , Duseja A , Bansal R 
Published: October 2024

Abstract
Disclosure: L. Das: None. S.K. Bhadada: None. A. Duseja: None. R. Bansal: None.
Introduction: Type 2 Diabetes mellitus (T2DM) predisposes to increased prevalence and severity of non-alcoholic fatty liver disease (NAFLD), but there are no approved therapies for NAFLD complicating T2DM. Further, weight loss, the cornerstone of management of NAFLD, is invariably associated with adverse bone health. This study aimed to evaluate the anti-steatotic and anti-fibrotic efficacy of oral semaglutide in T2DM with NAFLD and its effect on bone microarchitecture. Patients and Methods: Obese T2DM patients with NAFLD [steatosis defined as controlled attenuation parameter (CAP) &gt; 248dB/m with/without fibrosis [defined as liver stiffness measurement (LSM)] were recruited. Oral semaglutide was initiated at 3mg daily dose, followed by 4-weekly increments to 7mg and 14mg. Vibration-controlled transient elastography (FibroScan) was used to evaluate CAP and LSM. Steatosis and fibrosis were graded as per standard criteria (CAP: S0 &lt;248dB/m, S1 248-268, S2 268-280 and S3&gt;280; LSM: F0 &lt;6kPa, F2 ≥8.2, F3 ≥9.7, F4 ≥13.6) with F2-F4 grades constituting clinically relevant fibrosis (CRF). Body composition was analysed by DXA and bone microarchitecture by high-resolution peripheral quantitative CT. Results: There were 41 patients (49% males) with mean (± SD) age 50±9.2 years, mean BMI 35.6±6.1kg/m2 and median duration of T2DM 7 (IQR 2-12) years. All patients had steatosis (95% severe) and 70% had CRF. At 52 weeks, there was a significant reduction in the proportion of patients with steatosis (100% to 58%) and CRF (68% to 42%), with reduction in mean CAP and LSM (p&gt;0.05). Body weight [-6kg (3to13), p=0.002] reduced significantly, with concurrent reduction in fat percent (41 ± 8 to 39 ± 7, p = 0.06). There was significant HbA1c reduction [-1.1% (0.7to2.3), p=0.001] and improvement in HDL (41±12 to 50±13mg/dl, p=0.01). Baseline ALT was the only factor significantly greater in the responders (≥20% LSM reduction, 66.7% patients) as compared to non-responders (43±25 vs 23±3U/L, p =0.04). Tibial cortical volumetric BMD (923.3 ± 86.9 vs 915.5 ± 59.4, p=0.003) and trabecular inner volumetric BMD (125.8 ± 46.7 vs 113.2 ± 32.8, p=0.007) were significantly higher at 52 weeks than baseline without any significant changes in other cortical or trabecular parameters. Adverse effects included transient nausea and vomiting in 65% patients. Serum amylase and lipase increased non-significantly from baseline but there was no case of clinical pancreatitis. There was no worsening of retinopathy. Conclusion: Oral semaglutide was found to reduce proportion of patients with steatosis as well as CRF, with significant reduction in body weight, HbA1c, and improvement in HDL in this largest and longest interventional study, suggesting anti-steatotic and anti-fibrotic efficacy of the drug. Further, there was marginal improvement in volumetric BMD, which may provide an added benefit of this drug in NAFLD complicating T2DM.
Presentation: 6/2/2024