Long‐term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors

Hackett, Geoffrey; Cole, Nigel; Mulay, Akhilesh; Strange, Richard C.; Ramachandran, Sudarshan

doi:10.1111/bju.14536

Cited by 36 publications

(16 citation statements)

References 42 publications

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“…In fact there were fewer deaths (Figure 4), myocardial infarctions and strokes as compared with the control group (Table S1). Our observations are consistent with other studies showing reduced mortality in men with hypogonadism and T2DM receiving TTh 25,26 …”

Section: Discussionsupporting

confidence: 93%

“…Our observations are consistent with other studies showing reduced mortality in men with hypogonadism and T2DM receiving TTh. 25,26 For many decades, initiating prostate cancer or activating occult prostate cancer has been a concern when treating older men with testosterone. In the present study, the incidence of prostate cancer was significantly lower in the testosterone group compared to the control group (Table S1).…”

Section: Discussionmentioning

confidence: 99%

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Remission of type 2 diabetes following long‐term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11‐year data from a real‐world registry study

Haider¹,

Haider²,

Saad

et al. 2020

Diabetes Obesity Metabolism

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Aims: To investigate whether testosterone therapy (TTh) in men with hypogonadism and type 2 diabetes mellitus (T2DM) improves glycaemic control and insulin sensitivity, and results in remission of T2DM. Material and Methods: A total of 356 men who had total testosterone levels ≤12.1 nmol/L (350 ng/dL) and symptoms of hypogonadism were included in the study and followed up for 11 years. All patients received standard diabetes treatment and 178 patients additionally received parenteral testosterone undecanoate 1000 mg every 12 weeks following an initial 6-week interval. A control group comprised 178 hypogonadal patients who opted not to receive TTh. Results: Patients with hypogonadism and T2DM treated with testosterone had significant progressive and sustained reductions in fasting glucose, glycated haemoglobin (HbA1c) and fasting insulin over the treatment period. In the control group, fasting glucose, HbA1c and fasting insulin increased. Among the patients treated with testosterone 34.3% achieved remission of their diabetes and 46.6% of patients achieved normal glucose regulation. Of the testosterone-treated group, 83.1% reached the HbA1c target of 47.5 mmol/mol (6.5%) and 90% achieved the HbA1c target of 53.0 mmol/mol (7%). In contrast, no remission of diabetes or reductions in glucose or HbA1c levels were noted in the control group. There were fewer deaths, myocardial infarctions, strokes and diabetic complications in the testosterone-treated group. Conclusions: Long-term TTh in men with T2DM and hypogonadism improves glycaemic control and insulin resistance. Remission of diabetes occurred in one-third of the patients. TTh is potentially a novel additional therapy for men with T2DM and hypogonadism.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Remission of type 2 diabetes following long‐term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11‐year data from a real‐world registry study

Haider¹,

Haider²,

Saad

et al. 2020

Diabetes Obesity Metabolism

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“…As noted in Table 3, indeed TTh in overweight and obese men resulted in marked reduction in major cardiovascular adverse events. In contrast, untreated men experienced increased incidence of deaths and major adverse events including prostate cancer, confirming previous studies [32,34].…”

Section: Discussionsupporting

confidence: 87%

Differential effects of 11 years of long-term injectable testosterone undecanoate therapy on anthropometric and metabolic parameters in hypogonadal men with normal weight, overweight and obesity in comparison with untreated controls: real-world data from a controlled registry study

Saad

Doros

Haider³

et al. 2020

Int J Obes

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Background and significance Obesity is a chronic disease, warranting long-term medical intervention. We evaluated effects of testosterone (T) therapy (Th) in men with T deficiency with normal weight, overweight and obesity on anthropometric and metabolic parameters, compared with untreated men. Methods Hypogonadal men (n = 823) with total T ≤ 12.1 nmol/L (age: 60.6 ± 7.0 years) participated in an ongoing registry study. Among these men 474 (57.6%) were obese, 286 (34.8%) overweight and 63 (7.7%) had normal weight. T undecanoate injections were administered to 428 men and 395 remained untreated. Anthropometric and metabolic parameters were measured at least twice a year and changes adjusted for confounding factors to account for baseline differences between groups. Results Long-term TTh in hypogonadal men, irrespective of weight at baseline, produced improvements in body weight, waist circumference (WC) and body mass index (BMI). Furthermore, TTh decreased fasting blood glucose and HbA 1c and improved lipid profiles. Gradual decreases in blood pressure (systolic and diastolic) and pulse pressure occurred in men treated with T in each group. Marked reductions in mortality and major cardiovascular events were recorded in men receiving TTh. Conclusions Our findings demonstrate that TTh produces reductions in weight, WC, and BMI. There were 77 (19.5%) deaths in the untreated groups and 23 (5.4%) in the T-groups. Based on these findings we suggest that long-term TTh in overweight and obese hypogonadal men produces progressive and sustained clinically meaningful weight loss and that TTh may contribute to reductions in mortality and incident major adverse cardiovascular events.

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“…10,[12][13][14][15] In men with T2DM and adult-onset TD, testosterone therapy (TRT) can improve sexual health, increase lean mass and reduce body fat, fasting glycaemia, insulin resistance and all-cause mortality though importantly, not all men demonstrate beneficial effects. [15][16][17][18][19][20][21][22] Understanding the role of SHBG in this process is complicated by the finding that in adults, serum SHBG levels increase with age and demonstrate marked interand intra-individual variation. 23 Thus, in 857 men with T2DM, we found concentrations between 7.9 and 185.5 nmol/L.…”

Section: Introductionmentioning

confidence: 99%

Testosterone replacement therapy: Pre‐treatment sex hormone‐binding globulin levels and age may identify clinical subgroups

2020

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Background Testosterone replacement therapy (TRT) improves health in some but not all men with type 2 diabetes (T2DM) and adult‐onset testosterone deficiency (TD). Such heterogeneity is compatible with the concept of patient subgroups that respond differently to therapy. Objectives Use baseline SHBG and age to identify putative subgroups that demonstrate different responses in variables such as waist circumference and HbA1c following TRT. Materials and methods A randomized double‐blind trial approach was used to recruit and randomize men with T2DM and adult‐onset TD into placebo and TRT‐treated groups. Multiple regression was used to study differences between groups. Results Baseline SHBG and change in SHBG (∆SHBG) were inversely related in the TRT group. Both median values of SHBG and age mediated the effect of TRT on ∆SHBG depending on whether baseline values were ≤ or>median (28.1 nmol/L, 63 years, respectively). In men with both SHBG ≤ 28.1 nmol/L and age ≤ 63 years (subgroup 1), TRT was positively associated with ∆SHBG (c = 4.67, 95%CI 1.17‐8.16, P = .010) while in those with SHBG > 28.1 nmol/L and age > 63.1 years (subgroup 4) the association was inverse (c = −7.07, 95%CI −11.64 to −2.49, P = .003). The association between TRT and change (∆) in waist circumference, HbA1c and International Index of Erectile Function (IIEF) score differed between subgroups; in subgroup 4 but not subgroup 1, the therapy was significantly associated with ∆waist circumference, ∆HbA1c and ∆IIEF. Discussion Though the mechanism remains unclear, our finding of different responses to TRT in terms of change in waist circumference, HbA1c and IIEF score supports the concept of subgroups in men with T2DM and adult‐onset TD. Conclusion Our approach may provide a basis for identifying men who will or will not derive benefit from TRT though a larger study is required.

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Long‐term testosterone therapy in type 2 diabetes is associated with reduced mortality without improvement in conventional cardiovascular risk factors

Cited by 36 publications

References 42 publications

Remission of type 2 diabetes following long‐term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11‐year data from a real‐world registry study

Remission of type 2 diabetes following long‐term treatment with injectable testosterone undecanoate in patients with hypogonadism and type 2 diabetes: 11‐year data from a real‐world registry study

Differential effects of 11 years of long-term injectable testosterone undecanoate therapy on anthropometric and metabolic parameters in hypogonadal men with normal weight, overweight and obesity in comparison with untreated controls: real-world data from a controlled registry study

Testosterone replacement therapy: Pre‐treatment sex hormone‐binding globulin levels and age may identify clinical subgroups

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