Effects of Testosterone Undecanoate vs Placebo on Intrahepatic Fat Content in Overweight/Obese Men With T2DM or Prediabetes and Hypogonadism
Trial Parameters
Brief Summary
The epidemics of obesity, MeTSy, T2DM and CVD are increasing worldwide. Non-alcoholic fatty liver disease (NAFLD) is becoming recognized as a condition possibly involved in the pathogenesis of these diseases. The prevailing hypothesis for NAFLD pathogenesis is the 'two-hit' model, with insulin resistance and hyperinsulinemia playing essential roles, which have a plethora of effects on hepatic lipid metabolism and can lead to accumulation of triglycerides in hepatocytes. Accepted treatment for NAFLD is lifestyle modifications. Sex hormones might be relevant in T2DM development and treatment. Low testosterone (T) has deteriorating effects on glucose levels, and aggravates in obesity as aromatization of T is enhanced. T deficiency is related to increases of visceral fat accumulation and associated with development of NAFLD. T replacement might be a successful way in hypogonadism to treat obesity and counteract progression of MEtSy,T2DM or CVD driven by visceral fat accumulation or NAFLD. Primary Objective To investigate the effects on hepatic lipid content reduction of a therapy with Testosterone undecanoate 1000mg compared to placebo given for 52 weeks in patients with type 2 diabetes mellitus and hypogonadism.
Eligibility Criteria
Inclusion Criteria: * prediabetes/T2DM * male sex * HbA1c \>=5.7% -9.0% or fasting glucose \>=100mg/dl or postprandial glucose\>= 140mg/dl * Age \>=18 -75 years * BMI\>=25kg/m² * Hypogonadism assessed by laboratory testing (testosterone \< 4,04ng/ml (=14nmol/l) Metformin 8 weeks stable dose, SGLT2 inhibitors 3 months stable dose, DPP4 inhibitors 3 months stable dose, GLP1 RA 3 months stable dose and long acting insulin (basal insulin) 8 weeks stable dose * able and willing to not change diet and physical activity during enrollment in study * consent and able to give informed consent. Exclusion Criteria: * Current testosterone treatment or testosterone replacement within the last 12 month * Serum creatinine\>1,5mg/dl * Liver enzymes above 3 fold normal range * PSA\>4.0μg/l * Hematocrit\>50% * Known intolerance to testosterone undecanoate or any of its ingredients * Myocardial infarction within the last 12month * Stroke within the last 12 month * Untreated congestive heart disease * mali