Testosterone therapy (TTh) prevents progression from prediabetes to type 2 diabetes (T2DM) in hypogonadal: 9-year data from a registry study

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Testosterone therapy (TTh) prevents progression from prediabetes to type 2 diabetes (T2DM) in hypogonadal: 9-year data from a registry study F Saad 1,2, KS Haider 3, A Haider 3 1 Global Medical Affairs Andrology, Bayer AG, Berlin, Germany 2 Gulf Medical University School of Medicine, Ajman, United Arab Emirates 3 Private Urology Practice, Bremerhaven, Germany

Background: The recommended strategy to prevent progression from prediabetes to T2DM is weight loss. Method: Of 400 men with symptomatic hypogonadism, 45 (11.3%) had prediabetes defined by HbA 1c of 5.7-6.4%. Most men had presented to the urology office with complaints of erectile function or urinary function. All men men received testosterone undecanoate injections (TU) 1000 mg/12 weeks following an initial 6-week interval. No structured recommendations for lifestyle modifications were provided. Most measurements were performed 2 to 4 times a year for up to 11 years. 9-year data are presented.

20 Trough total testosterone (nmol/l) in 45 hypogonadal men with prediabetes on longterm treatment with testosterone undecanoate 19 18 17 16 15 14 13 12 11 10 9 8

HbA 1c (%) in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 6 5,9 5,8 5,7 5,6 5,5 5,4 5,3 5,2 5,1 5

Fasting glucose (mmol/l) in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 6 Testosterone 5,9 5,8 5,7 5,6 5,5 5,4 5,3 5,2 5,1 5 p<0.001 p<0.005 p<0.01 p<0.005 p<0.005 p<0.001 p<0.0005 NS * ; NS=non-significant

Triglyceride:HDL ratio in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 7,5 7 6,5 6 5,5 5 4,5 4 3,5 3

Weight (kg) in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 100 95 90 85 80

Waist circumference (cm) in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 105 100 95 90

BMI (kg/m 2 ) in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 33 32 31 30 29 28 27 26 25

Weight change (%) in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 0-5 -10-15 -20-25

Systolic and diastolic blood pressure (mmhg) in 45 hypogonadal men with prediabetes on long-term treatment with testosterone undecanoate 150 140 130 120 110 100 90 80 70 60

Prediabetes Nebido HAIDER 12 135 116 84-32 37,4 27,1 6,3 5,4 30 132 82 76-6 25,9 24 6,1 5,2 68 132 118 82-36 39 27,1 6,1 5,2 78 132 128 96-32 42,8 32,1 6,1 5,5 83 132 88 75-13 28,1 23,9 5,9 5,4 85 129 98 80-18 33,1 27 6,1 5,3 87 132 108 81-27 35,7 26,8 5,9 5,3 88 120 100 90-10 34,6 31,1 5,8 5,5 108 132 104 84-20 31,1 25,1 5,7 5 130 126 126 93-33 39,3 29 6,1 5,2 183 111 108 93-15 35,7 30,7 6,2 5,4 184 72 92 82-10 28,7 25,6 6,1 5 189 108 110 85-25 34,3 26,5 5,7 5,2 190 108 121 86-35 36,9 26,3 5,7 5,3 219 93 95 82-13 29,6 25,6 5,7 5 222 93 84 77-7 27,1 24,9 5,7 5 223 93 102 88-14 27,4 23,6 5,8 5,4 225 90 85 81-4 27,1 25,9 5,7 5 233 75 92 90-2 29,7 29,1 5,9 5,7 257 90 102 93-9 32,6 29,7 6,1 5,5 261 75 91 84-7 27,5 25,4 5,7 5,4 265 75 102 86-16 33,7 28,4 5,9 5,2 270 75 78 73-5 24,9 23,3 5,7 5,4 274 72 82 76-6 27,4 25,4 5,7 5,2 277 72 97 83-14 30,3 25,9 5,7 4,9 295 69 107 95-12 33,8 30 5,7 5,1 296 69 82 78-4 27,7 26,4 5,7 4,9 303 69 73 72-1 23,8 23,5 5,8 5,2 304 69 77 73-4 24,3 23 5,7 5,1 305 69 75 72-3 24,5 23,5 5,8 5,2 307 66 79 74-5 25,5 23,9 5,9 5,3 310 66 78 72-6 25,2 23,2 5,8 5,4 312 69 103 91-12 32,9 29 5,8 5,2 314 69 111 94-17 36,7 31 5,7 5,2 315 66 109 96-13 34 30 5,9 5,3 330 69 103 90-13 34 29,7 5,9 5 331 69 102 91-10 32,6 29 5,7 5,1 332 66 110 95-15 35,9 31 6,1 5,1 333 66 108 95-13 36,1 31,7 5,9 5 334 63 109 96-13 35,2 31 5,8 5,1 335 63 111 97-14 35 30,6 6,1 5 336 63 107 94-13 33,4 29,3 5,8 5,1 337 63 114 99-15 38,1 33,1 6,1 5,1 338 63 108 94-14 34,5 30 5,7 5 339 66 110 96-13 37,6 32,8 5,9 5 Individual patients: No progression from prediabetes to T2DM HbA 1c <5.7% (cut-off for prediabetes) HbA 1c 5.7% and <6.5% (cut-off for diabetes)

Conclusions Long-term TTh with TU in hypogonadal men with prediabetes completely prevented progression from prediabetes to type 2 diabetes. This effect may have been mediated by weight loss which was demonstrated by sustained reductions in weight and waist circumference. In addition, it is known that testosterone increases lean body mass and reduces fat mass, changes in body composition which are beneficial over and beyond weight loss alone.