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.
prediabetes/T2DM
male sex
HbA1c >=5.7% -9.0% or fasting glucose >=100mg/dl or postprandial glucose>= 140mg/dl
Age >=18 -75 years
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
Parallel
Testosterone Undecanoate
Drug1000mg/4ml i.m. initial, after 6 weeks, every 10 weeks thereafter
Placebo
DrugPlacebo Arm
Liver fat
Change in Liver fat content
body weight
change in body weight
waist, hip and neck circumference
change in waist, hip and neck circumference
insulin sensitivity
change in insulin sensitivity and Insulin secretion assessed by oGTT
Level of HbA1c
change in HbA1c from baseline to week 52
amount of body fat
Change in body fat, liver volume, visceral adipose tissue, subcutaneous adipose tissue, total adipose tissue and total lean tissue, myocardial and pancreatic fat and ventricular function
level of HbA1c
The occurrence of treat to target efficacy i.e. HbA1c \< 7.0 % or \< 6.5 %.
HbA1c reduction >=0.5%
The occurrence of a relative efficacy response. i.e. HbA1c lowering of at least 0.5%
mean daily glucose profile
The change from baseline in mean daily glucose profile assessed by 8 point glucose profiles
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Alexandra Kautzky-Willer
Lead sponsor
Medical University of Vienna
Sponsor institution
Bayer
Collaborator
