Objective : Prevalence of Non Alcoholic Fatty Liver Disease (NAFLD) is roughly 20–30% in the general population, but it reaches 50% in patients affected by Type 2 Diabetes Mellitus (T2DM). We sought to evaluate the effect of GLP-1 agonists and SGLT-2 inhibitors on NAFLD by measurement of “Fatty Liver Index” (FLI) in T2DM patients.
Methods : 58 patients treated with metformin, with or without insulin, were added with GLP-1 agonists or SGLT-2 inhibitors for poorly controlled diabetes (HbA1c >7.0%). Personal, bio-humoral data and FLI were assessed at baseline and 12 month later. FLI was calculated by the formula ey / (1 + ey) × 100, where y = 0.953 × ln(triglycerides, mg/dL) + 0.139 × BMI, kg/m2 + 0.718 × ln (GGT, U/L) + 0.053 × waist circumference, cm – 15.745.
Results : After 12 months of treatment both GLP-1 agonists and SGLT-2 inhibitors groups showed significantly lower BMI (-3.9% and -2.7%, respectively), waist circumference (-2.8% and -1.7%, respectively), fasting blood glucose (-14.3% and -18.3%, respectively), HbA1c (-12.8% and -13.2%, respectively), triglycerides (-18% and -15%, respectively) and FLI (-9-3% and -8.7%, respectively). SGLT-2 inhibitors also showed significant reduction of ALT (-15.1%) and total cholesterol (-12.5%). No differences were detected at follow up between the two groups. .
Several studies demonstrated positive effects of GLP-1 agonists on NAFLD of type 2 diabetic patients expressed by reduction of ALT and AST, intrahepatic lipids and histological resolution of NAFLD. The expression of GLP-1R in hepatocytes is still controversial, then, it is uncertain whether GLP-1 agonists act directly through hepatic GLP-1 receptor or indirectly via metabolic amelioration.
SGLT-2 inhibitors too have been demonstrated to reduce liver fat, improve ALT levels, reduce hepatocyte injury biomarkers and FLI. Positive effects on liver fat were also demonstrated both by CT scan and histological findings.
This is the first study that compared the effect of SGLT-2 inhibitors and GLP-1 agonists on FLI. Both drugs, at a similar extent, were able to reduce FLI. As expected, they induced a reduction of BMI, waist circumference, fasting plasma glucose, HbA1c, and triglycerides. The amelioration of FLI seemed to be dependent by the metabolic improvement, and independent by the mechanism of action, as no difference could be detected between the two drugs.
Conclusion : The study showed that in patients with T2DM and NAFLD, the addition of SGLT-2 inhibitors or GLP-1 agonists to metformin, with or without insulin, hesitated in a significant amelioration of FLI.
Division of Endocrinology,
Lecce, Puglia, Italy
Roberto Negro, MD, FACE, is Senior Assistant Physician at Endocrine Unit of “V. Fazzi” Hospital in Lecce (Italy) since 2005. Professor of Endocrinology at University of Parma, Italy (2007-2009). Reviewing Editor of Journal of Endocrinological Investigations (2009-2012). Fellow American College of Endocrinology (2011). Reviewing Editor of Journal of Clinical Endocrinology & Metabolism (2012-2016). He is author and co-author of more than 60 published papers, having Thyroid and Pregnancy as main field of interest. He has been part of the panel of experts appointed by the American Thyroid Association for the compilation of the Guidelines for the “Diagnosis and Management of Thyroid Disease during Pregnancy and Postpartum”, and by the European Thyroid Association for the compilation of the “Guidelines for Subclinical Hypothyroidism in Pregnancy and Childhood”.
Awards and Honors
2007 The Endocrine Society and Pfizer, Inc. International Award for Excellence in Published Clinical Research in The Journal of Clinical Endocrinology & Metabolism.
2008 The Endocrine Society and Pfizer, Inc. International Award for Excellence in Published Clinical Research in The Journal of Clinical Endocrinology & Metabolism.