Background: Prevalence of hypogonadism has been reported as high as 50% in men with T2DM. ADA Guidelines recommend assessment of hypogonadism in men with T2DM. Methods: In a registry of 865 men with hypogonadism, 361 men (41.7%) had T2DM. 183 received TU 1000 mg/12 weeks (T-group), 178 opted against treatment (CTRL). Changes over time between groups were compared and adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids and quality of life to account for baseline differences between the two groups. Results: Mean follow-up 8.7±3.1, baseline age: 60.7±5.5 (T-group) and 63.0±4.9 (CTRL) years. T-group: HbA1c progressively decreased by 3.7±0.2% at 12 years (unadjusted from 9.4±1.4% to 5.6±0.2%). CTRL: HbA1c increased by 3.2±0.2% (from 7.8±0.7% to 10.4±1.2%) (p<0.0001 for both). Fasting glucose (mmol/L) decreased in T-group by 1.9±0.1 (from 7.8±1.3 to 5.4±0.1) and increased in CTRL by 1.8±0.1 (from 6.3±0.7 to 8.0±1.2) (p<0.0001 for both). In the T-group, 89 men (48.6%) received insulin at baseline at a mean dose of 38.0±13.3 U/d. Dose requirement declined by 32.7±1.3 U/d (from 38.0±13.3 to 8.8±9.2) during the observation period. In CTRL, 69 men (38.8%) received insulin at baseline at a mean dose of 31.3±6.2 U/d. Dose requirement increased by 20.0±1.4 U/d (from 31.3±6.2 to 43.8±7.8) (p<0.0001 for both). HOMA-IR decreased by 8.0±0.3 (from 10.1±2.1 to 1.7±0.4) in the T-group and increased by 6.5±0.4 (from 7.3±1.3 to 14.3±2.3) in CTRL (p<0.0001 for both). In CTRL, 22 patients were started on insulin during the observation period. 37 patients had incident T2DM during the observation time. Conclusions: Long-term testosterone therapy with TU in men with hypogonadism and T2DM progressively improved glycemic control which deteriorated in untreated men. Disclosure F. Saad: Consultant; Self; Bayer AG, Stock/Shareholder; Self; AbbVie Inc., Bayer AG, Novo Nordisk. K. S. Haider: Other Relationship; Self; Bayer AG. A. Haider: Other Relationship; Self; Bayer AG. Funding Bayer AG