Sustained weight loss over 10 years in hypogonadal men with type 2 diabetes receiving testosterone in a registry study  
 

A Haider, G Doros, KS Haider, A Traish, F Saad



Background: Hypogonadism is highly prevalent in men with type 2 diabetes mellitus (T2DM) as well as obesity and can affect up to 50% of patients with either condition. 

Aim: To study long-term effectiveness and safety of testosterone undecanoate injections (TU) in a subgroup of hypogonadal men from an ongoing registry study in a urological setting.

Method: 
A registry of hypogonadal men was established in 2004 in a single urologist’s office. All men had testosterone ≤12.1 nmol/L. Of 776 patients, 286 (36.9%) had type 2 diabetes which had been diagnosed and is being treated elsewhere (family physician, diabetologist).
Of these men, 133 received TU 1000 mg/12 weeks (T-group) following an initial 6-week interval. 153 had opted against TTh for various reasons and served as controls (CTRL). Measurements were performed 1-4 times a year for up to 11 years and included, anthropometric parameters, glycaemic control and lipids. 10-year data are reported. 

Results:
Mean age at baseline was 61.8±5.4 years in the T-group and 64.2±4.6 years in CTRL. 

The majority of men were obese: 91% in the T-group and 72% in CTRL. In the T-group, 18% had excessive obesity, defined by BMI ≥40 kg/m2, in CTRL, 5%. Only 1 patient in the T-group and 5 in CTRL fell into the normal weight category.

Mean weight progressively decreased from 113.1±13.7 to 89.6±9.0 kg after 10 years in the T-group (p<0.0001). The decrease was statistically significant vs. previous year for the first 9 years, then continued without reaching statistical significance. In CTRL, mean weight remained stable from 100.8±12.9 to 99.2±12.9 kg (NS). The estimated adjusted difference between groups was -22.2 kg (p<0.0001). 

Mean waist circumference progressively decreased from 111.1±7.4 to 99.2±5.5 cm after 10 years in the T-group (p<0.0001). The decrease was statistically significant vs. previous year for the first 9 years, then continued without reaching statistical significance. In CTRL, mean waist circumference fluctuated but dropped during the last 4 years from 115.1±12.8 at baseline to 111.8±13.0 cm at 10 years (NS vs. baseline). The estimated adjusted difference between groups was -13.5 cm (p<0.0001).

Mean BMI progressively decreased from 36.2±4.4 to 29.1±2.9 kg/m2 after 10 years in the T-group (p<0.0001). The decrease was statistically significant vs. previous year for the first 9 years, then continued without reaching statistical significance. In CTRL, mean BMI remained stable from 32.3±4.6 to 32.7±5.1 kg/m2 (NS). The estimated adjusted difference between groups was -7.2 kg/m2 (p<0.0001).

Per cent weight loss was -20.1±5.3% after 10 years in the T-group (p<0.0001). In CTRL, weight change was 0.5±5.9% (NS). The estimated adjusted difference between groups was -20.4% (p<0.0001). 

Per cent reduction in waist circumference was -11.4±3.6% after 10 years in the T-group (p<0.0001). In CTRL, the adjusted per cent change in waist circumference remained neutral at 0.0±4.9% (NS). The estimated adjusted difference between groups was -12.1% (p<0.0001).

Mean waist:height ratio decreased from 0.63±0.04 to 0.57±0.03 after 10 years (p<0.0001). The decrease was statistically significant vs. previous year for the first 9 years. In CTRL, waist:height ratio remained stable from 0.65±0.08 to 0.64±0.09 (NS). The estimated adjusted difference between groups was -0.08 (p<0.0001).

In the T-group, all but 1 patient lost weight, despite the fact that 54 men were on insulin. The only patient who gained 1 kg of weight during the observation time was a man whose testosterone treatment was interrupted following a diagnosis of prostate cancer. In CTRL, almost all men gained weight. Only 12 men lost weight, and 5 men did not have any change in weight.

In the T-group, 4 patients (3%) died of non-cardiovascular events. There were no non-fatal major adverse cardiovascular events (MACE). In CTRL, 24 patients (15.7%) died. 50 non-fatal MACE occurred (26 myocardial infarctions, 24 strokes).

No patient dropped out. Since all injections were administered in the doctor’s office and documented, there was a 100% adherence to testosterone treatment. 

Discussion: 
Limitations: The study was not designed to investigate effects of testosterone on obesity in men with T2DM. Patients were not randomized as in a medical office setting, neither randomisation nor placebo-control were an option. Patients in the T-group had higher baseline weight while waist circumference at baseline was higher in CTRL. 
Strengths: The long duration of follow-up, the excellent medication adherence to testosterone, and close interdisciplinary collaboration with the diabetologists. All patients had the same opportunity to attend lifestyle courses at the diabetes centre. 
Conclusion: 
Long-term treatment with TU in hypogonadal men with T2DM resulted in substantial and sustained weight loss in comparison to untreated controls. Correcting hypogonadism in men with T2DM supports standard diabetes treatment including lifestyle instructions.