Endocrine Abstracts

Background and aims: There is evidence that new anti-diabetic drugs may limit liver disease progression, reduce liver fat and normalize serum aminotranferase levels in patients with NAFLD. We compared the effectiveness of new drug classes on liver fat in T2DM patients by means of surrogate markers.

Materials and methods: In an observational retrospective study we analysed the 12-month time-courses of clinical and anthropometric data of T2DM cases treated by SGLT2-inhibitors (n=131), DPP4-inhibitors (n=102), and GLP-1R-agonists (n=232), alone or in combination with metformin/sulfonylureas, together with a group of 154 cases treated by GPs with sulfonylureas±metformin and/or pioglitazone (CONT). The aminotransferase levels, the Fatty Liver Index (FLI-a validated measure of steatosis) and the Fib-4 score (a surrogate marker of fibrosis) were measured at 6-month intervals.

Results: In the whole population, mean BMI was 34.7±7.0 kg/m², ALT levels 35.8±24.8 U/l. A1c levels were higher in SGLT-2Is and GLP-1RAs compared to other classes. ALT levels were higher in GLP-1RA treated cases, and lower in DPP-4I-treated patients, compared to other classes. At 12-mo follow-up changes in ALT levels were present in GLP-1RA and SGLT-2I groups. At baseline most cases were classified as steatosis (89%) or indeterminate (9%) by FLI. In a logistic regression analysis, treatment with SGLT-2Is was the only therapy associated with significant improvement in FLI class from steatosis to indeterminate/no steatosis (15% of cases) (OR, 5.12; 95% CI, 1.50–17.5), after adjustment for age, gender, BMI, ALT and HbA1c at baseline. No significant changes in Fib-4 score were measured at follow-up in any group.

Conclusion: SGLT-2Is and GLP-1RAs are particularly effective in metabolic control, and are associated with improved liver enzymes and markers of steatosis in T2DM at 12-month follow-up, without any difference in fibrosis markers.