Outcomes of an observational registry research of males with type 2 diabetes and hypogonadism (low testosterone) counsel that as much as 12 years of testosterone injections each 3 months could enhance glycemic management.
A second research in the identical cohort hints that this remedy could decrease the chance for cardiovascular occasions and enhance survival ― however that research has inherent weaknesses and doesn’t tackle security issues, consultants warning.
Farid Saad, MD, who not too long ago retired from Medical Affairs Andrology, Bayer, Berlin, Germany, and Karim S. Haider, MD, a urologist at a clinic in Bremerhaven, Germany, introduced the most recent outcomes from the 2 observational research in an oral session on the American Diabetes Affiliation (ADA) 81st Scientific Periods earlier in the summertime.
Invited to remark, Maarten Albersen, MD, cautioned: “These are nonrandomized information; therefore, any laborious conclusions on the comparability between testosterone and management are not possible because of the truth that these teams are unadjusted for all potential confounders.”
Earlier this 12 months, a randomized managed trial (T4DM) that was published in Lancet Diabetes and Endocrinology confirmed that testosterone would possibly forestall or revert kind 2 diabetes in males enrolled in a life-style program, though there have been security issues with this trial.
A big, ongoing randomized section 4 trial, TRAVERSE, is predicted to ship ends in a few years, famous Albersen, a member of the European Affiliation of Urology Scientific Workplace, from Leuven College, Leuven, Belgium.
Glycemic Management, however at What Value?
Saad and Haider introduced findings from 361 males with kind 2 diabetes who underwent remedy in a urology clinic in Bremerhaven, Germany. Of these sufferers, 183 males opted to obtain testosterone undecanoate (Nebido) 1000 mg, which was administered by injection each 3 months, and 178 males opted to not obtain this remedy (management sufferers).
Saad introduced the glycemic management findings.
“We beforehand printed a research that confirmed that testosterone undecanoate injections had been related to prevention of development from prediabetes to diabetes (Diabetes Care. 2019;42:1104-1111),” he instructed Medscape Medical Information in an e mail.
This was adopted by a research of 11 years of remedy within the sufferers within the present analysis, which was introduced on the European and Worldwide Congress on Obesity (ECOICO 2020), as previously reported and subsequently printed (Diabetes Obes Metab. 2020;22:2055-2068).
The present research confirmed that amongst males with hypogonadism and kind 2 diabetes, from baseline to 12 years, imply A1c decreased from 9.4% to five.6% within the group that acquired testosterone undecanoate injections (T-group) and elevated from 7.8% to 10.4% within the management group.
“The randomized managed trial [T4DM]…confirms the helpful results of testosterone plus train on glycemia and metabolic profile (with train solely as a management group),” Albersen mentioned.
However within the T4DM trial, a security set off for a hematocrit >54% was met by 22% of sufferers receiving testosterone, vs 1% of sufferers within the management group, “and it’s recognized that an elevated hematocrit is a threat issue for thromboembolic occasions,” he identified.
Mortality, MACE, and Diabetic Problems
Haider reported findings relating to mortality, main antagonistic cardiovascular occasions (MACE; myocardial infarction [MI] or stroke), and diabetic issues.
At baseline, greater than a 3rd of sufferers (38%) in every group had a historical past of heart problems.
In comparison with sufferers within the management group, these within the T-group had been youthful (imply age, 61 vs 63 years) however in any other case had a worse threat issue profile. They had been extra more likely to smoke (41% vs 38%), they’d larger imply physique mass index (36 vs 33 kg/m2), larger systolic blood strain (163 vs 145 mm Hg), larger LDL-cholesterol degree (4.7 vs 4.1 mmol/L), and better A1c (9.4% vs 7.8%; P < .0001 for all).
However throughout follow-up, fewer sufferers within the T-group than within the management group died (15 sufferers [8.2%] vs 61 sufferers [34%]).
Not one of the sufferers within the T-group had an MI or stroke, in comparison with 56 circumstances of MI (31.5%) and 56 circumstances of stroke (31.5%) within the management group.
Albersen says these outcomes “don’t make sense. No MI and stroke within the T-group appears considerably weird (in a gaggle with larger up-front threat).”
He questioned how strict the follow-up was and famous that the pattern was too small to supply definitive conclusions about mortality.
With regard to microvascular issues, fewer sufferers within the T-group than within the management group developed retinopathy (3.3% vs 16.9%), nephropathy (0.01% vs 2.8%), or diabetic foot syndrome (0% vs 10.1%)
Ready for TRAVERSE Trial Outcomes for CV Security of Testosterone
Albersen famous that the 5-year, AbbVie-sponsored section 4 trial of testosterone gel in 6000 males, TRAVERSE, “is awaited to make clear cardiovascular results of testosterone remedy in a randomized vogue…as there have been issues on the cardiovascular security.” That trial is predicted to be accomplished in June 2022.
In a commentary that accompanied the publication of the T4DM research earlier this 12 months, Naveed Sattar, MD, of the College of Glasgow, Glasgow, United Kingdom, and colleagues famous, “The US Meals and Drug Administration agree [that caution is needed] and have mandated that any product for age-related hypogonadism ought to have a cardiovascular end result trial.” This led to the TRAVERSE research.
“It’s hoped the ensuing information will at the least present the cardiovascular security of testosterone remedies in males with low serum testosterone (<10.4 nmol/L) and at the least one symptom of hypogonadism,” the editorialists write.
Bayer AG (beforehand Schering AG) contributed partial funding for statistical analyses and information entry of the 2 research. Haider is a speaker for and receives analysis and journey assist from Bayer. Saad is a guide for Bayer AG and owns shares for Bayer AG and AbbVie. Aboumarzouk and Albersen have disclosed no related monetary relationships. Sattar has acquired private charges and a analysis grant from Boehringer Ingelheim and private charges from Amgen, AstraZeneca, Eli Lilly, Merck Sharp & Dohme, Novartis, Novo Nordisk, Pfizer, and Sanofi. The disclosures of the opposite editorialists are with the editorial.
American Diabetes Affiliation (ADA) 81st Scientific Periods: Scientific Periods. Introduced on June 28, 2021. 238-OR, 240-OR.