Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial

Fernández‐García, José Carlos; Barrios‐Rodríguez, Rocío; Asenjo-Plaza, Maite; Ramos‐Molina, Bruno; Molina‐Vega, María; Guzmán-Guzmán, Antonio; Moreno-León, Luis; Yubero‐Serrano, Elena M.; Rius-Díaz, Francisca; Valdés, Sergio; Martínez‐González, Miguel Ángel; Jiménez-Moleón, José Juan; Tinahones, Francisco J.

doi:10.1016/j.metabol.2022.155290

Cited by 12 publications

(4 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…In insulin‐resistant non‐diabetic obese men with hypogonadism, the combination of metformin plus testosterone replacement treatment compared to testosterone and metformin administered separately provided a more significant increase in serum TT and FT. However, it did not further ameliorate the erectile function 32 . In a sub‐study of a randomized, double‐blind, cross‐over, placebo‐controlled trial, 24 men with impaired glucose tolerance or T2D diagnosed with hypogonadism (serum TT ≤10.4 nmol/L) were randomized to receive metformin 2 g/day plus clomiphene or placebo (12 weeks apart by 6 weeks of pharmacological wash out).…”

Section: Discussionmentioning

confidence: 99%

“…However, it did not further ameliorate the erectile function. 32 In a sub-study of a randomized, double-blind, crossover, placebo-controlled trial, 24 men with impaired glucose tolerance or T2D diagnosed with hypogonadism (serum TT ≤10.4 nmol/L) were randomized to receive metformin 2 g/day plus clomiphene or placebo (12 weeks apart by 6 weeks of pharmacological wash out). The overall sexual function assessed by the IIEF15 and qADAM scores was not modified significantly.…”

Section: Effect Of 1-unit Increase In Baseline Parametersmentioning

confidence: 99%

See 1 more Smart Citation

Long‐acting glucagon‐like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study

Lisco,

Bartolomeo,

De Tullio

et al. 2023

Andrology

View full text Add to dashboard Cite

IntroductionThe pharmacological management of erectile dysfunction (ED) in type 2 diabetes (T2D) is challenging as ED has a multifactorial etiology. The therapeutic potential of certain antihyperglycemic medications, such as glucagon‐like peptide 1 receptor agonists (GLP‐1RAs), has yet to be entirely studied in this setting.Material and methodsA retrospective cohort study was conducted on 108 outpatients (median age 60 [56, 65] years) with T2D complaining of ED. Data were extracted from a database referring to patients with a 1‐year follow‐up on stable treatment with metformin alone (n = 45) and GLP‐1RAs as an add‐on to metformin (n = 63). Erectile function was assessed by the 5‐item International Index of Erectile Function (IIEF5) at baseline and after 1 year of stable treatment . Values were compared between baseline (T0) and after 12 months of treatment (T12).ResultsED was confirmed in all at baseline, with an IIEF5 score range between 13 and 19 points. After 12 months of treatment, glucose management was better in patients treated with GLP‐1RAs plus metformin (HbA1c T0: 8.3 ± 0.2 vs. HbA1c T12: 7% ± 0.3%, p < 0.0001) than in those on metformin alone (HbA1c T0: 7 ± 0.5 vs. HbA1c T12: 7.3 ± 0.4, p = 0.0007). GLP‐1RAs plus metformin over metformin alone resulted in a significant weight loss (−5.82 ± 0.69 kg, p < 0.0001), reduction in waist circumference (−4.99 ± 0.6 cm, p < 0.0001), improvement in HbA1c (−0.56% ± 0.13%, p < 0.0001), and fasting plasma glucose (−25.54 ± 3.09 mg/dL, p < 0.0001), increase in total (+41.41 ± 6.11 ng/dL, p < 0.0001) and free (0.44 ± 0.09 ng/dL, p < 0.0001) testosterone levels, and gain in self‐reported erectile function (IIEF5 score: +2.26 ± 0.26, p < 0.0001). The gain in the IIEF5 score was more relevant in patients with higher baseline IIEF5 score (estimated coefficient: 0.16 ± 0.08, p = 0.045), those having carotid stenosis (0.50 ± 0.24, p = 0.045), and showing weight loss from baseline (−0.08 ± 0.03, p = 0.013). The leading determinant of the final IIEF5 score was a 1‐year treatment with GLP‐1RAs plus metformin over metformin alone (2.74 ± 0.53, p < 0.0001).DiscussionGLP‐1RAs plus metformin over metformin alone improved ED regardless of different background characteristics of patients and partially irrespective of therapeutic targets achieved after 12 months of treatment. GLP‐1RAs may have induced positive vasculature effects, resulting in improved erectile function in T2D.ConclusionDue to the retrospective nature of the study, a potential cause–effect relationship between the use of GLP‐1RAs plus metformin over metformin alone in improving ED cannot be verified and confirmed. Randomized clinical trials are needed to provide evidence supporting the use of GLP‐1RAs for treating ED in T2D.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Effect Of 1-unit Increase In Baseline Parametersmentioning

confidence: 99%

Long‐acting glucagon‐like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study

Lisco,

Bartolomeo,

De Tullio

et al. 2023

Andrology

View full text Add to dashboard Cite

show abstract

“…Несмотря на актуальность изучения влияния коррекции метаболического синдрома, в частности показателей углеводного обмена и массы тела на эндогенную продукцию тестостерона у мужчин с СД2 и ассоциированным с ним функциональным гипогонадизмом, в литературе встречается крайне ограниченное число работ, посвященных данному вопросу [15,16,34,35].…”

Section: обсуждение дополнительных результатов исследованияunclassified

Evaluation of the effect of testosterone replacement therapy with a transdermal testosterone on glycemic control in men with type 2 diabetes mellitus

Rozhivanov,

Chernova,

Ioutsi

et al. 2024

Diabetes mellitus

View full text Add to dashboard Cite

BACKGROUND: It is important to evaluate the effect of androgen replacement therapy on glycemic control.AIMS: Assessment of the effect of transdermal testosterone therapy on glycemic control in men with hypogonadism and T2DM.MATERIALS AND METHODS: The prospective, comparative study included 300 men aged 55[49;61] years: men receiving both glucose-lowering therapy (GLT) and transdermal testosterone; and patients receiving only GLT. Observation period 1 year. A medical history, a questionnaire for symptoms of androgen deficiency, and measurement of total testosterone and glycated hemoglobin were carried out. Groups were compared using nonparametric methods.RESULTS: Patients receiving androgen replacement therapy in combination with GLT at both 6 and 12 months from the moment of inclusion in the study, they had a statistically significantly higher level of total testosterone and less severity of symptoms of androgen deficiency. When assessing the magnitude of changes in the studied parameters, it was found that patients receiving testosterone replacement therapy (TRT) were characterized by a statistically significantly more pronounced decrease in the level of glycated hemoglobin (average difference 0,3%). In 29 (20,4% (95% ДИ 13,8–27,0)) men who received only GLT, hypogonadism was eliminated. In 3 patients from the TRT group, a pathological increase in the level of total blood PSA was observed, and therefore TRT was discontinued. An increase in hemoglobin above the reference value (>172 g/l) was detected in 8% and 1,3% of men on TRT and without correction of hypogonadism, respectively, p=0,011.CONCLUSIONS: The combination of transdermal TRT and GLT has a positive effect on glycemic control, which is manifested by a decrease in glycated hemoglobin to a greater extent than when using GLT alone. Normalization of testosterone levels leads to a decrease in the symptoms of androgen deficiency, which is accompanied by an improvement in quality of life. Elimination of hypogonadism only with GLT is possible in a small number of cases.

show abstract

“…The clinical trial consisted of 82 participants with obesity and low testosterone levels, that were randomized to metformin (n=19), testosterone (n=24), metformin plus testosterone (n=20), or placebo (n=19), for 12 months. Plasma samples of participants were collected in the Department of Endocrinology and Nutrition at the Virgen de la Victoria University Hospital (Malaga, Spain) as described previously (Fernández-García et al 2022).…”

Section: Participantsmentioning

confidence: 99%

Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome

Vinicki,

Pribić,

Vučković

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

With aging, there is a correlation between a decline in the body’s ability to maintain regular functioning and greater susceptibility to age-related diseases. Therapeutic interventions targeting the underlying biological changes of aging hold promise for preventing or delaying multiple age-related diseases. Metformin, a drug commonly used for diabetes treatment, has emerged as a potential gerotherapeutic agent due to its established safety record and preclinical and clinical data on its anti-aging effects. Glycosylation, one of the most common and complex co- and post-translational protein modifications, plays a crucial role in regulating protein function and has been linked to aging and various diseases. Changes in IgG glycosylation patterns have been observed with age, and these alterations may serve as valuable biomarkers for disease predisposition, diagnosis, treatment monitoring, and overall health assessment. In this study, we analyzed the IgG glycosylation patterns of individuals under treatment with metformin, testosterone, metformin plus testosterone and placebo, and investigated the longitudinal changes in glycosylation over time. We observed statistically significant differences in the IgG glycome composition between participants on testosterone therapy and placebo, with decreased agalactosylation and increased galactosylation and sialylation. However, metformin therapy did not result in statistically significant changes in glycosylation patterns. These findings contribute to our understanding of the impact of therapeutic interventions on IgG glycosylation and confirm the value of IgG glycosylation as a significant biomarker, capable of assessing biological age using the GlycanAge index and providing insight into overall health compared to chronological age.

show abstract

Metformin, testosterone, or both in men with obesity and low testosterone: A double-blind, parallel-group, randomized controlled trial

Cited by 12 publications

References 35 publications

Long‐acting glucagon‐like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study

Long‐acting glucagon‐like peptide 1 receptor agonists boost erectile function in men with type 2 diabetes mellitus complaining of erectile dysfunction: A retrospective cohort study

Evaluation of the effect of testosterone replacement therapy with a transdermal testosterone on glycemic control in men with type 2 diabetes mellitus

Effects of testosterone and metformin on the GlycanAge index of biological age and the composition of the IgG glycome

Contact Info

Product

Resources

About