Farid Saad

Euro Weight Loss-2015Frankfurt, Germany

August 18 – 20, 2015

Progressive weight loss in 104 obese hypogonadal men with type 2 diabetes mellitus (T2DM) treated with testosterone

undecanoate up to 84 months in an observational registry study

Saad F1,2, Haider A3, Doros G4, Traish A5

1Global Medical Affairs Andrology, Bayer Pharma, Berlin, Germany; 2Gulf Medical University, Ajman, UAE; 3Private Urology Practice, Bremerhaven, Germany; 4Department for Epidemiology and Statistics, Boston University School of Public Health, Boston, Mass, USA; 6Department of Biochemistry and Department of

Urology, Boston University School of Medicine, Boston, Mass, USA

Proportion of Hypogonadism in 103 Consecutive Male Patients with Diabetes

Dhindsa S et al. J Clin Endocrinol Metab 89(11): 5462-5468 (2004)

33

44

36

10

15

20

25

30

35

40

45

50

free T (<0.225 nmol/L) total T (<10.4 nmol/L) bio T (<5.2 nmol/L)

Kapoor D et al. Diabetes Care 30: 911-917 (2007)

51 5250

10

15

20

25

30

35

40

45

50

55

60

total T <= 12 nmol/L bioavailable T <= 4 nmol/L free T < 0.255 nmol/L

Proportion (%) of Hypogonadism in 355 Male Patients with Type 2 Diabetes (mean age 58 years, range: 32 – 83)

Dhindsa S et al. Diab Care 33: 1186-1192 (2010)

Prevalence (%) of Hypogonadism in Diabetic and Non-Diabetic Obese Men Separated into Quartiles of Age

0

10

20

30

40

50

60

70

Quartile 1 (45-52) N=408/55

Quartile 2 (53-59) N=378/82

Quartile 3 (60-68) N=326/136

Quartile 4 (69-91)N=339/125

no T2DM T2DM

p<0.01

p<0.01

p=0.05

Proportion of Type 2 Diabetes and Prediabetes in 1023 Hypogonadal Men from 3 German Centers

31

23

33

16

31

54

0

10

20

30

40

50

60

type 2 diabetes prediabetes

Hamburg Bremerhaven Muenster

Haider A et al. J Urol 193: 80-86 (2015)

Background:

There is a robust bi-directional association between obesity and testosterone (T) deficiency (hypogonadism) in men with a prevalence of hypogonadism in obese men as high as 52%. We investigated effects of normalising T in obese hypogonadal men on anthropometric parameters.

Methods:

Cumulative, prospective, observational registry study of 340 men with T levels ≤12.1 nmol/L receiving parenteral T undecanoate 1000 mg/12 weeks following an initial 6-week interval for up to seven years. A subgroup of 104 men (30.6% of the total group) with obesity and T2DM was analysed.

8

10

12

14

16

18

20

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

* *

+ 5.32 ± 0.4 nmol/L

* *

*

Total Testosterone (nmol/L)

p=0.0012p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

*p=NS

*p=0.0126

p=NS

#

*p<0.0001 vs baseline # p<0.0001 vs previous year

90

95

100

105

110

115

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

**#

*

- 22.87 ± 0.77 kg

*p=NS

104N= 104 104 102 87 73 71 65 58 54 53 50 2543 38

*

*

*p=0.0026

Weight (kg)

#

#

p=0.0001

29

30

31

32

33

34

35

36

37

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

**

*

- 7.4 ± 0.25 kg/m2

*p=NS

p=0.0021

#

Body Mass Index (BMI, kg/m2)

*#

*

*#

104N= 104 104 102 87 73 71 65 58 54 53 50 2543 38

p=0.0001

99

100

101

102

103

104

105

106

107

108

109

110

111

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

Waist Circumference (cm)

**#

- 11.89 ± 0.3 cm

*p=0.0025

104N= 104 104 102 87 73 71 65 58 54 53 50 2543 38

*#

*#

*#

*p=0.0126

0

10

20

30

40

50

60

70

80

90

100

3 months 6 months 9 months 12 months end point

increase any reduction ≥ 5% ≥ 10% ≥ 15% ≥ 20%%

Proportion of Patients with Varying Degrees of Weight Loss

95

100

105

110

115

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

*

- 23.64 ± 1.92 mg/dl

*p=NS* *

*p=NS

Fasting Glucose (mg/dl)

p=0.001

p=0.0006p=NS

p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

5,5

5,7

5,9

6,1

6,3

6,5

6,7

6,9

7,1

7,3

7,5

7,7

7,9

8,1

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

*

- 2.32 ± 0.07%

*p=0.0002

* p=0.0416

p=0.0001

HbA1c (%)

#

*#

104N= 67 62 58 56 43 45 40 37 35 35 31 1529 25

*#

Patients Reaching HbA1c Target of ≤ 7.0%

100%

0%

10%

90%

0

10

20

30

40

50

60

70

80

90

100

no yes no yes

baseline endpoint

Patients Reaching HbA1c Target of ≤ 6.5%

4%

96%

3%8

97%

0

10

20

30

40

50

60

70

80

90

100

no yes no yes

baseline endpoint

130

135

140

145

150

155

160

165

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

**

*

- 24.72 ± 1.11 mmHg

*p=NS

**

p=NS

Systolic Blood Pressure (mmHg)

p=0.0007

p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

*p=NS

75

80

85

90

95

100

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

**

*

- 21.94 ± 0.93 mmHg

*p=NS

* *p=NS

Diastolic Blood Pressure (mmHg)

p=0.0005 p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

*p=0.0253

74

74,5

75

75,5

76

76,5

77

77,5

78

78,5

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

- 3.77 ± 0.66 bpm

*p=NS

*p=NS

Heart Rate (bpm)

p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

*p=NS

*p=NS

*p=NS

59

59,5

60

60,5

61

61,5

62

62,5

63

63,5

64

64,5

65

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

- 2.8 ± 0.93

*p=NS

*p=NS

Pulse Pressure

p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

*p=NS

*p=NS

*p=NS

180

190

200

210

220

230

240

250

260

270

280

290

300

310

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

*

- 116.04 ± 3.59 mg/dl

*p=NS

**

*p=NS

Total Cholesterol (mg/dl)

p=0.0067

p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

p=0.0359

60

62

64

66

68

70

72

74

76

78

80

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

+ 12.36 ± 0.69 mg/dl

* * *

HDL Cholesterol (mg/dl)

p=NS p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

p=0.0011

*p=NS

*p=0.0001

120

130

140

150

160

170

180

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

- 41.24 ± 2.73 mg/dl

*

* *

LDL Cholesterol (mg/dl)

p=0.0363

p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

p=0.0002

*p=NS

*p=0.0002

180

190

200

210

220

230

240

250

260

270

280

290

300

310

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

*

- 111.41 ± 4.74 mg/dl

*p=NS

* * p=NS

Triglycerides (mg/dl)

p=0.0006p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

*p=NS

2

2,5

3

3,5

4

4,5

5

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

*

- 2.36 ± 0.07

*p=NS

* * *p=0.0444

Total Cholesterol:HDL Ratio

p=0.0102p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

p=NS

2

2,5

3

3,5

4

4,5

5

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

*

- 2.31 ± 0.09

*p=NS

* * *p=0.0451

Triglycerides:HDL Ratio

p=0.0027p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

p=NS

18

20

22

24

26

28

30

32

34

36

38

40

42

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

AST ALT

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

- 20.51 ± 1.14 U/L

* *

*

Liver Transaminases (U/L)

p=NS p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

#

*p=NS *

p=NS

*p=NS

- 22.48 ± 1.22 U/L

*#

* *p=NS p=NS

*p=NS *

p=NS

*p=NS

0

0,5

1

1,5

2

2,5

3

3,5

4

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

*

*

- 5.05 ± 0.57 mg/dl

*p=NS

* *p=NS

CRP (mg/dl)

p=0.0165p=NS

104N= 104 103 102 87 73 71 65 58 54 53 50 2543 38

*p=NS

*p=0.0003

17

22

27

32

37

42

47

52

0 3 6 9 12 15 18 21 24 27 30 33 36 39 42 45 48 51 54 57 60 63 66 69 72 75 78 81 84

*p<0.0001 vs baseline # p<0.0001 vs previous year

**

- 34.49 ± 0.7

*p=NS

#

Quality of Life Measured by Aging Males‘ Symptoms Scale (AMS)

104N= 104 104 102 87 73 71 65 58 54 53 50 2543 38

*p=NS

*p=NS

*p=NS

*p=NS

There was no major adverse cardiovascular event (MACE).

No patient dropped out.

Summary and Conclusions

Obesity and type 2 diabetes are common in men with testosterone deficiency and vice versa.

Testosterone therapy induces meaningful and sustained weight loss.

Long-term testosterone therapy progressively and sustainably improves metabolic parameters and glycaemic control thus improving the cardiometabolic risk profile.

These effects require long-term treatment.

Testosterone treatment was well tolerated.

Treatment adherence was excellent suggesting a high level of patient satisfaction.

farid.saad@bayer.com

Euro Weight Loss – 2016 Website:http://weightloss.global-summit.com/

europe/

Meet the eminent gathering once again atEuro Weight Loss-2016

Vienna, AustriaSeptember 19-21, 2016