(398) Remission of Type 2 Diabetes, Mortality, and Major Adverse Cardiovascular Events in Men with Hypogonadism and Type 2 Diabetes Receiving Long-term Testosterone Therapy in Comparison to an Untreated Control Group in a Urological Registry Study
Authors: Haider K S , Haider A , Doros G , Traish A , Saad F 
Published: May 2023

Abstract

Introduction
We had reported previously that 34.3% of patients with hypogonadism and type 2 diabetes (T2DM) receiving testosterone therapy (TTh) up to 11 years in our registry study achieved remission of their T2DM after a mean time of 8.6±2.9 years (Haider KS et al. Diabet Obes Metab 2020;22:2055-2068). Remission is defined as discontinuation of anti-diabetic medication while maintaining HbA1c within the non-diabetic range for at least three months.

Objective
to investigate effects of long-term TTh up to 13 years in men with hypogonadism and T2DM on glycemic control, remission of T2DM, mortality, and major adverse cardiovascular events (MACE).

Methods
In an ongoing registry study in men with hypogonadism (total testosterone ≤350 ng/mL and at least moderate symptoms on the Aging Males’ Symptoms scale, AMS) in a single urology office, 370 men had type 2 diabetes. 190 men received testosterone undecanoate (TU) injections 1000 mg/12 weeks following an initial 6-week interval (T-group), 180 opted against TTh and served as controls (CTRL). Patients’ T2DM was treated at the local diabetes center which included mandatory lifestyle education. Glycemic control (HbA1c) was measured and insulin resistance (HOMA-IR) calculated at each or each other visit. Absolute measures with standard deviations (SDs) as well as changes over time, adjusted for age, weight, waist circumference, fasting glucose, blood pressure, lipids, and quality of life to account for baseline differences between groups, are reported for a duration of 13 years.

Results
Mean (median) follow-up: T-group 9.0±3.4 (9), CTRL 9.7±3.2 (11) years, total observation time: T-group 1703, CTRL 1747 patient-years. Baseline age was 60.0±6.4 (T-group) and 63.0±4.9 years (CTRL) (p&lt;0.0001). 71 patients (37.4%) in the T-group and 74 (41.1%) in CTRL had a history of cardiovascular disease (myocardial infarction MI, stroke, or coronary artery disease diagnosis) (p&lt;0.05). Baseline smoking prevalence was 41.6% (79 men) in the T-group and 37.4% (67 men) in CTRL (p=0.415). HbA1c decreased from 9.5±1.4% to 5.5±1.2% in the T-group and increased from 7.8±0.7% to 10.5±1.2% in CTRL (means ± SDs). Mean adjusted change from baseline (least squares means ± SEs) at 13 years was -3.7±0.2 (T-group) and +3.4±1.2 (CTRL) (p&lt;0.0001 for all). HOMA-IR decreased from 10.2±2.1 to 1.5±0.3 in the T-group and increased from 7.3±1.3 to 14.8±2.5 in CTRL. Mean adjusted change from baseline at 13 years was -8.3±0.3 (T-group) and +6.8±0.4 (CTRL) (p&lt;0.0001 for all). In the T-group, 108 patients (56.8%) went into remission. The median time to remission was 87 months. During the entire observation period, 21 patients (11.1%) died in the T-group vs. 62 (34.4%) in CTRL (p&lt;0.0001). Major adverse cardiovascular events (MACE): in the T-group, there were no cases of MI or stroke. In CTRL, there were 62 cases of MI (34.4%) and 51 cases of stroke (28.3%).

Conclusions
Long-term TTh in men with hypogonadism and T2DM improves glycemic control and insulin resistance and reduces mortality and MACE, compared to untreated controls. Every other patient receiving TTh achieves remission of T2DM.

Disclosure
Yes, this is sponsored by industry/sponsor: Bayer AG, Berlin, Germany.

Clarification
Industry funding only - investigator initiated and executed study.
Any of the authors act as a consultant, employee or shareholder of an industry for: Bayer AG.