GLP-1 Agonisten- und SGLT-2 Inhibitoren-Therapie bei Patienten mit nicht alkoholischer Fettlebererkrankung und Diabetes mellitus Typ 2

Einleitung Die nicht-alkoholische Fettlebererkrankung (NAFLD) ist eine häufig auftretende Erkrankung mit steigender Prävalenz (aktuell 25%). Neben Adipositas stellt der Diabetes mellitus Typ 2 einen wichtigen Risikofaktor dar. Auf der anderen Seite haben Patienten mit NAFLD ein erhöhtes Risiko zur Entwicklung eines Diabetes mellitus Typ 2. Bisher existiert keine evidenzbasierte Pharmakotherapie, weswegen der Effekt verschiedener Antidiabetika auf die NAFLD durch multiple Studien überprüft wird. In dieser Studie wird untersucht, ob Sodium-Glucose Cotransporter-2 (SGLT-2) Inhibitoren oder Glucagon-like Peptide-1 (GLP-1) Agonisten eine Verbesserung der Steatose bei Patienten mit NAFLD und Diabetes mellitus Typ 2 bewirken. Patienten und Methoden 39 Patienten (49% Frauen, Alter 57,7 ± 10,9 Jahre) mit Diabetes mellitus Typ 2 und NAFLD, die mittels controlled attenuation parameter (CAP)-Messung definiert werden konnte (CAP-Wert ≥ 215 dB/m), wurden rekrutiert. Es erfolgten eine Screening-Untersuchung und Kontrolluntersuchungen in einem Beobachtungszeitraum von 6 Monaten in Bezug auf die Steatose, die Lebersteifigkeit (Vibration Controlled Transient Elastography) und die Körperzusammensetzung (Bioelectrical Impedance Analysis), ferner zur Leberfunktion sowie zum Glukose- und Lipidstoffwechsel. Ergebnisse Es wurde eine signifikante (P = 0,026) Reduktion der Steatosis hepatis in der gesamten Kohorte beobachtet. Diesbezüglich ergab sich eine absolute mediane Reduktion der CAP-Werte von -32 dB/m (-58 – 32 dB/m), die einer medianen relativen Reduktion von 9% entspricht. Ebenfalls wurden signifikante Verbesserungen der Leberenzyme (Alanin Aminotransferase, γ-Glutamyltranspherase), des Körpergewichts und des Body Mass Index (-2.5 ± 3.3 kg und -0.9 ± 1.2 kg/m2) sowie der Parameter des Glukosestoffwechsels (Hämoglobin A1c , Nüchternglukose und Homeostatic Model Assessment-estimated Insulin Resistance) nachgewiesen. Die Subgruppenanalyse ergab eine signifikante (P = 0,014) Reduktion der Steatose ausschließlich in der Gruppe der Patienten, die mit SGLT-2 Inhibitoren behandelt wurden. Hier zeigte sich eine absolute mediane CAP-Reduktion von -38 dB/m (-58 – 9 dB/m). Schlussfolgerungen SGLT-2 Inhibitoren haben einen positiven Einfluss auf die Glukose-Homöostase, das Körpergewicht sowie die NAFLD. Daher könnten diese Medikamente bei Patienten mit Diabetes mellitus Typ 2 und begleitender NAFLD bevorzugt verabreicht werden und sollten weiter untersucht werden.Treatment with Glucagon-like Peptide-1 (GLP-1) analogues and Sodium-Glucose Cotransporter-2 (SGLT-2) inhibitors in patients with non-alcoholic liver disease and diabetes mellitus type 2 Introduction and aim Non-alcoholic fatty liver disease (NAFLD) is believed to be the hepatic manifestation of metabolic syndrome and is currently the main cause of chronic liver disease in Western countries. NAFLD affects 80% of patients with type 2 diabetes, and plenty of studies report that insulin resistance is the primary determinant of its pathogenesis. Considering the lack of evidence-based pharmacotherapy for NAFLD, diabetes-related drugs are being tested. The aim of this study is to investigate whether SGLT-2 inhibitors or GLP-1 agonists improve hepatic fat accumulation in patients with type 2 diabetes. Patients and methods Overall, 39 patients (49% women, age 57.7 ± 10.9 years) with type 2 diabetes and hepatic steatosis (defined by controlled attenuation parameter [CAP] values ≥ 215 dB/m) were prospectively recruited and observed during the initiation of clinical therapy with either SGLT-2 inhibitors or GLP-1 agonists. Patients were observed for 6 months and were assessed for the following: hepatic steatosis and liver stiffness (Vibration Controlled Transient Elastography); body composition (Bioelectrical Impedance Analysis); glucose and lipid-metabolism as well as surrogate markers of liver function. Results A significant reduction of median liver fat contents by 9% (P = 0.026) was observed in the whole cohort after 6 months (absolute median CAP decrease -32 dB/m, -58 – 32 dB/m). This improvement was accompanied by significant reductions in liver function tests (reductions of alanine aminotransferase and γ-Glutamyltranspherase activities). Furthermore significant improvements in body weight, body mass index (-2.5 ± 3.3 kg and -0.9 ± 1.2 kg/m2, respectively) and glucose homeostasis (hemoglobin A1c, fasting plasma glucose and Homeostatic Model Assessment-estimated Insulin Resistance) were observed. Subgroup analysis revealed significant (P = 0,014) liver-related benefits to primarily occur in patients receiving SGLT-2 inhibitors (absolute median CAP decrease -38 dB/m, -58 – 9 dB/m). Conclusions SGLT-2 inhibitors improve hepatic steatosis parallel to glucose-homeostasis and body weight in patients with type 2 diabetes. Further studies should substantiate the positive effect of SGLT-2 inhibitors in larger groups of patients

Noninvasive monitoring of liver fat during treatment with GLP‐1 analogues and SGLT‐2 inhibitors in a real‐world setting

Introduction: Patients with NAFLD have a two‐fold increased risk of diabetes, and conversely, NAFLD affects up to 80% of patients with type 2 diabetes. Due to the co‐occurrence of both diseases and the lack of approved pharmacotherapy for NAFLD, the anti‐steatogenic potential of diabetes‐related drugs is being explored. In this study, we aim to monitor liver fat noninvasively during treatment with SGLT‐2 inhibitors or GLP‐1 analogues in a real‐world setting. Methods: Overall, 39 patients (49% women, age 57.7 ± 10.9 years) with type 2 diabetes and hepatic steatosis (defined by controlled attenuation parameter [CAP] values ≥ 215 dB/m) were observed for 6 months and routinely monitored with respect to hepatic fat contents and liver stiffness (VCTE); body composition (BIA); and blood biochemistry, including liver function tests (LFTs), serum lipids and glucose metabolism markers. Results: Median liver fat contents were significantly (P = .026) reduced by 9% in patients taking either SGLT‐2 (n = 22) or GLP‐1 (n = 17) for 6 months (absolute median CAP decrease: −32 dB/m [−58 to 32 dB/m]). In parallel, serum ALT and γ‐GT activities decreased significantly (P = .002 and P = .049, respectively). These improvements were accompanied by significant (P < .0001) changes to body weight and BMI (−2.5 ± 3.3 kg and −0.9 ± 1.2 kg/m2, respectively) and glucose homeostasis, with significant reductions in HbA1c and fasting plasma glucose (FDG) (both P < .0001). Of note, significant reductions of intrahepatic lipid contents occured in patients receiving SGLT‐2 inhibitors only. Conclusions: In this real‐world observational evaluation of fatty liver monitored noninvasively in patients with type 2 diabetes treated with either SGLT2 or GLP‐1, improvements in measures of hepatic steatosis, glucose and weight parameters were observed after 6 months, with significant reductions of intrahepatic lipid contents seen specifically in the SGLT2 subgroup