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Cited by 109Sexual function and dysfunction studiesHormonal and reproductive studiesDiabetes Treatment and Management

Adding liraglutide to lifestyle changes, metformin and testosterone therapy boosts erectile function in diabetic obese men with overt hypogonadism

Open access
Giagulli, V. A., Carbone, M. D., Ramunni, M. I., Licchelli, B., De Pergola, G., Sabbà, C., Guastamacchia, E., Triggiani, V.·2015·Andrology
DOI 10.1111/andr.12099
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Abstract

Summary: The aim of this retrospective observational study was to evaluate whether adding liraglutide to lifestyle changes, metformin (Met) and testosterone replacement therapy (TRT), by means of improving weight and glycaemic control, could boost erectile function in type 2 diabetic obese men with overt hypogonadism and erectile dysfunction (ED) in a ‘real‐life setting’. Forty‐three obese, diabetic and hypogonadal men (aged 45–59 years) were evaluated because of complaining about the recent onset of ED. They were subdivided into two groups according to whether hypogonadism occurred after puberty (G1; n = 30: 25 with dysfunctional hypogonadism and 5 with acquired hypogonadotropic hypogonadism) or before puberty (G2; n = 13: 10 with Klinefelter's syndrome and 3 with idiopathic hypogonadotropic hypogonadism). Both G1 and G2 patients were given a combination of testosterone (T) [testosterone undecanoate (TU) 1000 mg/every 12 weeks] and Met (2000–3000 mg/day) for 1 year. In the poor responders (N) to this therapy in terms of glycaemic target (G1N: n = 16; G2N: n = 10), liraglutide (L) (1.2 μg/day) was added for a second year, while the good responders (Y) to T + Met (G1Y: 14/30 and G2Y: 3/13) continued this two drugs regimen therapy for another year. All patients were asked to fill in the International Index of Erectile Function (IIEF 15) questionnaire before starting TU plus Met (T1) and after 12 months (T2) and 24 months (T3) of treatment. Patients underwent a clinical examination and a determination of serum sex hormone binding globulin (SHBG), total testosterone (T) and glycosylated haemoglobin (HbA1c) at T1, T2 and T3. At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)], while T turned out to be within the range of young men. L added to TU and Met regimen in G1N and G2N allowed these patients to reach not only the glycaemic target [HbA1c = <7.5% (<58 nmol/mol)] and a significant reduction in body weight (p < 0.01), but also a further increase in SHBG (p < 0.05) and T (p < 0.01) plasma levels as well as a significant increment of IIEF score (T3). Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score and they showed a significant rise in serum HbA1c (p < 0.05) and weight (p < 0.04) compared with the assessments at T2. These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred). Furthermore, in case of insufficient metabolic control the addition of L to TRT and Met regimen allows to achieve serum T levels in the range of healthy men, as well as to reach glycaemic target and to lower weight, leading to a considerable improvement of ED.

AI snapshot

Written from the paper’s full text.

TL;DR

In a 2-year retrospective observational study of 43 obese men with type 2 diabetes, overt hypogonadism, and erectile dysfunction, adding liraglutide to testosterone undecanoate plus metformin in poor glycaemic responders improved weight, HbA1c, testosterone/SHBG, and IIEF erectile function scores. Good responders who continued testosterone plus metformin alone showed partial metabolic and erectile-function failure by 24 months.

Key findings

  • After 12 months of testosterone undecanoate plus metformin, all patients improved ED and metabolic parameters, but did not reach glycaemic goals (HbA1c >7.5% / >58 mmol/mol); testosterone rose into the young-men range.
  • In poor responders, adding liraglutide for a second year produced further weight loss and glycaemic target attainment: G1N HbA1c 9.1±0.4%→8.3±0.3%→7.3±0.3%, weight 102.7±9.1→99.0±7.6→93.7±6.3 kg, IIEF 12.2±2.2→14.6±1.7→19.9±2.0; G2N HbA1c 8.8±0.8→8.2±0.3→7.4±0.6%, weight 105.3±9.8→102.5±7.1→98.0±8.3 kg, IIEF 14.2±1.8→16.5±1.6→19.9±1.1.
  • Good responders continuing testosterone plus metformin showed partial failure at T3: G1Y IIEF 12.2±2.5→14.7±2.0→14.3±1.9 (T3 vs T2 p<0.44), HbA1c 8.2±0.3→7.0±0.1→7.5±0.2 (p<0.05), weight 95.0±6.2→91.4±5.4→92.2±6.0 kg (p<0.04); G2Y had slight rises in weight, WC, BMI, and DBP (data not shown).
  • Safety: no major adverse cardiovascular events or prostate cancer; haematocrit and PSA rose but remained within normal range; two G1 participants reported vomiting and nausea during the first month of liraglutide.

Methods

  • Retrospective observational, 2-year, single-physician study at a secondary referral endocrinology centre (Conversano Hospital, Bari, Italy), using outpatient clinical records. Participants were 43 obese men with type 2 diabetes, overt hypogonadism, and recent ED; G1 (post-pubertal onset) n=30 (25 dysfunctional hypogonadism, 5 acquired hypogonadotropic hypogonadism), G2 (pre-pubertal onset) n=13 (10 Klinefelter’s syndrome, 3 idiopathic hypogonadotropic hypogonadism). Inclusion required HbA1c >8%, BMI >30 kg/m², total testosterone <300 ng/dL and free testosterone <65 pg/mL, and IIEF <14.
  • All received lifestyle changes (1500±200 kcal Mediterranean diet; brisk walking 150 min/week), metformin 2000–3000 mg/day, and testosterone undecanoate 1000 mg IM every 12 weeks for 1 year. Poor responders (G1N n=16; G2N n=10) added liraglutide 1.2 lg/day for a second year; good responders (G1Y 14/30; G2Y 3/13) continued testosterone plus metformin.
  • Outcomes at T1, T2, and T3 included IIEF 15, SHBG, total testosterone, HbA1c, anthropometrics, lipids, PSA, haematocrit, and digital rectal examination. Statistics used Mann–Whitney U-test between groups, paired two-tailed Student’s t-test within groups, p<0.05 significance, SPSS version 10.0.

Limitations

  • Stated by the authors: retrospective observational design, small number of participants, and the liraglutide effect cannot be separated from patient selection in the absence of an untreated control group.
  • Evident from the text: single physician/single centre, no randomization or placebo, and baseline differences between groups (e.g., age, diabetes duration, glycaemia, DBP, total cholesterol, LDL, triglycerides, IIEF).
  • Evident from the text: good versus poor responders were defined by treatment response, so confounding by indication is likely; some G2Y T3 data are not shown.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1111/andr.12099

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 65 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    After 12 months of combined testosterone undecanoate and metformin, each patient obtained an improvement of erectile dysfunction (p < 0.01).

    “At T2, each patient obtained an improvement of ED (p < 0.01)”
    Quote in the paperSubstantial claim
  • Findingown data

    Adding liraglutide to testosterone undecanoate and metformin in G1N and G2N allowed a further increase in testosterone plasma levels (p < 0.01).

    “and T (p < 0.01) plasma levels”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The improvements observed after adding liraglutide are attributable to liraglutide rather than to continuation of testosterone plus metformin, lifestyle changes, or unmeasured differences between poor and good responders.
  • Findingown data

    Adding liraglutide to testosterone undecanoate and metformin in G1N and G2N allowed a further increase in SHBG (p < 0.05).

    “but also a further increase in SHBG (p < 0.05)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The improvements observed after adding liraglutide are attributable to liraglutide rather than to continuation of testosterone plus metformin, lifestyle changes, or unmeasured differences between poor and good responders.
  • Findingown data

    At T3, G1Y and G2Y who received combined testosterone replacement therapy and metformin for the second year showed no improvement of the IIEF score.

    “Conversely, at T3 G1Y and G2Y, who received the combined therapy with TRT and Met for the second year, showed a partial failure of that treatment given that there was no improvement of the IIEF score”
    Quote in the paperSubstantial claim
  • Findingown data

    Adding liraglutide to testosterone undecanoate and metformin in G1N and G2N allowed a significant reduction in body weight (p < 0.01).

    “and a significant reduction in body weight (p < 0.01)”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The improvements observed after adding liraglutide are attributable to liraglutide rather than to continuation of testosterone plus metformin, lifestyle changes, or unmeasured differences between poor and good responders.
  • May combine two claims. 24
  • Classified as probably not a substantial claim. 23
  • The quote only partly states this claim. 2

  • May combine two claims.

    Findingown data

    After 12 months of combined testosterone undecanoate and metformin, each patient obtained improvement of metabolic parameters without reaching glycaemic goals (HbA1c >7.5%).

    “At T2, each patient obtained an improvement of ED (p < 0.01) and of the metabolic parameters without reaching, however, the glycaemic goals [HbA1c = >7.5% (>58 mmol/mol)]”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    G1 patients were older and affected by diabetes for a longer time than G2 men and showed poor metabolic control and a worse IIEF score.

    “the G1 patients who were older and affected by diabetes for a longer time when compared to the G2 men, showed a poor metabolic control and a worse IIEF score.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In G1Y at T3, weight (+0.8 ± 0.9%; p < 0.04) and waist circumference (+1.6 ± 1.3%; p < 0.01) significantly increased.

    “Conversely, in G1Y participants at the end of the observation (T3) both weight (+0.8 Æ 0.9%; p < 0.04) and WC (+1.6 Æ 1.3%; p < 0.01) significantly increased”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Serum SHBG was higher than T1 values in G1Y men only at T2 (+1.5 ± 1.3%; p < 0.02) but not at T3.

    “while it was higher than the values determined at T1 in G1Y men only at T2 (+1.5 Æ 1.3%; p < 0.02) but not at T3”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    None of the participants complained of major adverse cardiovascular events or prostate cancer throughout the entire observation period.

    “None complained of the major adverse cardiovascular events or of prostate cancer throughout the entire period of the observation.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Two participants in G1 complained of vomiting and nausea during the first month of liraglutide therapy, which did not cause dropout from treatment.

    “only two participants belonging to G1 group complained of vomiting and nausea during the first month of therapy with L which, however, did not cause the dropout of this treatment.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Neither clinical signs (BMI), metabolic parameters (HbA1c, TC, LDL) nor the IIEF score reached the values considered appropriate treatment targets for young adult obese subjects with type 2 diabetes without severe complications.

    “neither clinical signs (BMI), metabolic parameter (HbA1c, TC and LDL) nor the IIEF score reached those values that were considered as appropriate targets for the treatment in young adult obese subjects affected by T2DM without severe complications (Apovian et al., 2015;Handelsman et al., 2015;Inzucchi et al., 2015;Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Cheng A”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Apovian et al., 2015

      Not checked in the free run.

    • cites Handelsman et al., 2015

      Not checked in the free run.

    • cites Inzucchi et al., 2015

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Serum SHBG was statistically increased at T2 (+1.1 ± 1.7%; p < 0.05) and T3 (+1.5 ± 1.0%; p < 0.01) in G1N and G2N.

    “Serum SHBG, however, was statistically increased at T2 (+1.1 Æ 1.7%; p < 0.05) and T3 (+1.5 Æ 1.0%; p < 0.01) in G1N and G2N”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingown data

    Three G2Y participants presented a slight rise in weight, waist circumference, BMI and diastolic blood pressure after 2 years of metformin and testosterone undecanoate at T3 compared with T2.

    “presented a slight rise in weight, WC, BMI and DBP values after 2 years of Met and TU combined therapy at the end of the study (T3) in comparison with second point in time (T2)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In G1Y at T3, systolic and diastolic blood pressure values were higher than at T2 and very close to T1.

    “while SBP and DBP values were higher than those assessed at T2 and very close to the measures at T1”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    G1Y patients presented a statistically significant rise in glycaemia (+7.5 ± 9.1 mg/dL; p < 0.05) and plasma HbA1c levels (+0.2 ± 0.1%; p < 0.05) at T3.

    “presented a statistically raise in Gly (+7.5 Æ 9.1 mg/dL; p < 0.05) and plasma HbA1c levels (+0.2 Æ 0.1% (T3); p < 0.05) at the end of our study (T3)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    The addition of liraglutide in poor responders at T3 improved weight, waist circumference, BMI and systolic blood pressure in both G1N and G2N.

    “The addition of L in poor responders (T3) improved these parameters in both groups (G1N and G2N)”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: The improvements observed after adding liraglutide are attributable to liraglutide rather than to continuation of testosterone plus metformin, lifestyle changes, or unmeasured differences between poor and good responders.

  • May combine two claims.

    Findingcitation

    In G1N and G2N, combined metformin and testosterone undecanoate significantly improved serum glycaemia, HbA1c, calculated LDL and triglycerides compared with baseline, but did not fulfil criteria for treatment of adult diabetic subjects.

    “Although in G1N and G2N the combined therapy with Met and TU significantly improved both serum Gly, HbA1c and plasma lipid parameters such as calculated serum LDL and TG in comparison with baseline characteristics (T1) (Tables 2 and 5), they did not fulfil those criteria stated by major International Societies”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingreasoning

    Circulating SHBG significantly rose at T2 but not at T3 in G1Y, and at T2 and T3 in G1N and G2N whenever metabolic control and especially the glycaemic target were reached.

    “circulating SHBG significantly rose at T2 (but not at T3) in G1Y as well as at T2 and T3 in G1N and G2N whenever the metabolic control and especially the glycaemic target have been reached (Tables 2, 3 and 5).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    Hypogonadism, metabolic syndrome, type 2 diabetes mellitus and erectile dysfunction in adult men are related.

    “Recently several studies and a meta-analysis have highlighted the relationship between hypogonadism, metabolic syndrome (MetS), T2DM (Andersson et al., 1994;Dhindsa et al., 2004;Ding et al., 2006;Kapoor et al., 2007;Grossmann et al., 2008) and ED in adult men”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Andersson et al., 1994

      Not checked in the free run.

    • cites Dhindsa et al., 2004

      Not checked in the free run.

    • cites Ding et al., 2006

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Long-duration testosterone replacement therapy in hypogonadal men with obesity and/or type 2 diabetes results in significant fat loss and achievement of stable metabolic control.

    “Recently, in uncontrolled studies conducted in a large number of hypogonadal men with obesity and/or T2DM, long duration TRT was shown to result in both a significant fat loss and the achievement of stable metabolic control”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Saad et al., 2013

      Not checked in the free run.

    • cites Zitzmann et al., 2013

      Not checked in the free run.

  • The quote only partly states this claim.

    Interpretationown data

    In case of insufficient metabolic control, addition of liraglutide to testosterone replacement therapy and metformin allows lowering weight.

    “and to lower weight”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The improvements observed after adding liraglutide are attributable to liraglutide rather than to continuation of testosterone plus metformin, lifestyle changes, or unmeasured differences between poor and good responders.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    The contribution of testosterone replacement therapy in obese diabetic men with testosterone deficit and erectile dysfunction to weight loss, metabolic control and erectile dysfunction is debated.

    “the contribution of TRT in obese diabetic men with T deficit and ED related to the weight loss, the improvement of metabolic control and even ED, is debated”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites Seftel et al., 2004

      Not checked in the free run.

    • cites Lewis et al., 2010

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    • cites Glina et al., 2013

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    GLP-1 agonists have efficacious glucose-lowering properties and a sustained weight-reducing effect in type 2 diabetic subjects, even more than metformin.

    “glucagon-like peptide-1 (GLP-1) agonists have both efficacious glucose-lowering properties and a sustained weight-reducing effect in T2DM subjects, even more than metformin (Met)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Robinson et al., 2013

      Not checked in the free run.

    • cites Inzucchi et al., 2015

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Diabetes mellitus, obesity, hypertension and dyslipidemia are main risk factors for developing erectile dysfunction in men with or without overt hypogonadism.

    “Diabetes mellitus, obesity, hypertension and dyslipidemia have been reported as main risk factors for developing erectile dysfunction (ED) in men with or without overt hypogonadism”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Seftel et al., 2004

      Not checked in the free run.

    • cites Lewis et al., 2010

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    In diabetic men, duration of disease, age and peripheral neuropathy are directly associated with erectile dysfunction severity, as is poor glycaemic control.

    “In diabetic men, the duration of the disease, age and peripheral neuropathy are directly associated with ED severity, as does poor glycaemic control”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Romero et al., 2000

      Not checked in the free run.

    • cites Wesslle et al., 2011

      Not checked in the free run.

  • The quote only partly states this claim.

    Interpretationown data

    In case of insufficient metabolic control, addition of liraglutide to testosterone replacement therapy and metformin allows reaching the glycaemic target.

    “as well as to reach glycaemic target”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The improvements observed after adding liraglutide are attributable to liraglutide rather than to continuation of testosterone plus metformin, lifestyle changes, or unmeasured differences between poor and good responders.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Men with both pre-pubertal and post-pubertal onset hypogonadism could develop type 2 diabetes mellitus during their life span.

    “Men with both pre-pubertal (i.e.Klinfelter syndrome) and post-pubertal onset hypogonadism could develop type 2 diabetes mellitus (T2DM) during their life span”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Pei et al., 1998

      Not checked in the free run.

    • cites Bojesen et al., 2006

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Age and obesity are key drivers for metabolic diseases and hypogonadism, especially in adult and ageing men.

    “Both age and obesity (Kaufman & Vermeulen, 2005) have been recognized as key drivers for metabolic diseases and hypogonadism, especially in adult and ageing men.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kaufman & Vermeulen, 2005

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  • May combine two claims.

    Premisecitation

    Obesity is a modifiable factor, and when obese subjects lose weight, testosterone levels increase.

    “However, at variance with age, obesity is a modifiable factor, and when obese subjects lose weight, T levels increase”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Corona et al., 2013

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In an in vitro study, GLP-1 raised lipolysis in adipocytes in a dose-dependent manner.

    “while in an in vitro study, GLP-1 was able to raise lipolysis in adipocytes in a dose-dependent manner (Vendrell et al., 2011;Russo et al., 2015).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Vendrell et al., 2011

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    • cites Russo et al., 2015

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Metformin is generally considered a drug with a weight-neutral effect.

    “while Met, beside its universally well-known antiglycaemic role, is generally considered as a drug with weightneutral effect (Handelsman et al., 2015;Inzucchi et al., 2015)”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Handelsman et al., 2015

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    • cites Inzucchi et al., 2015

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Increasing serum testosterone by letrozole during a weekly hyperinsulinemic-euglycaemic clamp raised serum glucose-dependent insulinotropic polypeptide and insulin sensitivity in healthy young men.

    “increasing serum T by letrozole (aromatase inhibitor) therapy during a weekly hyperinsulinemic-euglycaemic clamp, was shown to bring about a rise in serum levels of glucose-dependent insulinotropic polypeptide and in insulin sensitivity in a group of healthy young men (Lapauw et al., 2010).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Lapauw et al., 2010

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    GLP-1 treatment reduced circulating total cholesterol in overweight and/or obese subjects, whether diabetic or not.

    “a meta-analysis study proved that GLP-1 treatment reduced circulating TC in overweight and/or obesity subjects either diabetics or not (Visboll et al., 2012).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Visboll et al., 2012

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    Study design and conductnone given

    All participants signed an informed consent at the time of the first clinical visit as recommended by good clinical practice.

    “All participants signed an informed consent at the time of the first clinical visit as recommended by good clinical practise.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Premisecitation

    GLP-1 agonists reduce weight, blood pressure and total cholesterol in obese patients with and without diabetes.

    “the well-known properties of GLP-1 agonists of reducing weight, blood pressure and TC in obese patients with and without diabetes (Visboll et al., 2012;Robinson et al., 2013)”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Visboll et al., 2012

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    • cites Robinson et al., 2013

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    No variables in the study turned out to be skewed.

    “Since no variables in the study turned out to be skewed, all data were given as the mean of the raw data Æ SD unless otherwise stated.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Everyone declared to have been compliant with the diet guidelines.

    “Everyone declared to have been compliant to the diet guidelines.”
    Quote in the paperNot a substantial claim
    • Rests on an assumption: Self-reported adherence to the diet guidelines reflects actual adherence.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    All assays showed intra- and inter-assay coefficients of variation below 8% and 10%, respectively.

    “all these methods showed an intra-and inter-assay coefficient of variation <8 and <10%, respectively.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Testosterone treatment might decrease insulin resistance by promoting commitment of pluripotent stem cells into the myogenic lineage, inhibiting their differentiation into mature adipocytes, and regulating their metabolism.

    “several lines of evidence argue that T treatment might decrease insulin resistance by means of promoting the commitment of pluripotent stem cells into the myogenic lineage and inhibiting their differentiation into mature adipocytes as well as regulating their metabolism in ways that lowers insulin resistance (Singh et al., 2003)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Singh et al., 2003

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  • May combine two claims.

    Interpretationreasoning

    The effects of GLP-1 agonists would be expected to have a beneficial effect on metabolic targets and on the vascular system, and hence on erectile dysfunction.

    “which would be expected to have a beneficial effect both on metabolic targets (Canadian Diabetes Association Clinical Practice Guidelines Expert Committee, Cheng AY, 2013;International Diabetes Federation Guideline Development Group, 2014;Handelsman et al., 2015;Inzucchi et al., 2015) and on the vascular system (and hence on ED)”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    Liraglutide treatment led to greater weight loss and improved insulin sensitivity in overweight and/or obese individuals.

    “Similarly, L treatment led to greater weight loss and improved insulin sensitivity in overweight and/or obese individuals (Kim et al., 2013).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Kim et al., 2013

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  • Classified as probably not a substantial claim.

    Study design and conductcitation

    A validated multi-dimensional self-report instrument for evaluation of male sex function, the IIEF 15, was administered to the patients.

    “a validated multi-dimensional self-report instrument for the evaluation of male sex function known as IIEF 15 (Rosen et al., 2002) were administered to our patients”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Rosen et al., 2002

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  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The study protocol agreed with the 2000 version of the Declaration of Helsinki and was approved by the Local Ethical Committee of the University of Bari (September 2014, n = 4545).

    “The study protocol agreed with the 2000 version of the Declaration of Helsinki and was approved by the Local Ethical Committee (September, 2014: n = 4545) of the University of Bari.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Metformin is not considered to have an intrinsic positive effect on the lipid profile.

    “and as not having an intrinsic positive effect on the lipid profile (Wulffel e et al., 2004)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Wulffel e et al., 2004

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Testosterone replacement therapy can reduce serum total cholesterol, especially in men with lower testosterone levels.

    “In a meta-analysis Isidori et al. (2005) demonstrated that TRT can reduce serum TC especially in men with lower T levels”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Isidori et al., 2005

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  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The baseline data of the two groups were comparable with those reported in the literature.

    “The baseline data of the two groups were comparable with those that have been reported in the literature so far”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Romero et al., 2000

      Not checked in the free run.

    • cites Wesslle et al., 2011

      Not checked in the free run.

  • May combine two claims.

    Study design and conductreasoning

    The study was conducted in a real-life setting for a long observational period.

    “it was conducted in a 'real-life setting' for a long observational period”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The rise in SHBG might be due to improvement of insulin resistance through weight loss and achievement of metabolic goals.

    “This result might be due to the improvement of insulin resistance by means of both the weight loss (Corona et al., 2013) and the achievement of metabolic goals (Tong et al., 2014).”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites Corona et al., 2013

      Not checked in the free run.

    • cites Tong et al., 2014

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Previous randomized, placebo-controlled studies were shorter and often performed in well-controlled patients.

    “while the previous randomized, placebo-controlled studies were shorter and often performed in well-controlled patients (Corona et al., 2014a;International Diabetes Federation Guideline Development Group, 2014).”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Corona et al., 2014a

      Not checked in the free run.

    • cites International Diabetes Federation Guideline Development Group, 2014

      Not checked in the free run.

45 of 45

  • The paper relies on this without support.

    The improvements observed after adding liraglutide are attributable to liraglutide rather than to continuation of testosterone plus metformin, lifestyle changes, or unmeasured differences between poor and good responders.

    “These results suggest that TRT could improve clinical and metabolic parameters in obese, type 2 diabetic men with ED and overt hypogonadism (independently of when T deficit occurred).”

  • The paper relies on this without support.

    Self-reported adherence to the diet guidelines reflects actual adherence.

    “Everyone declared to have been compliant to the diet guidelines.”
2 of 2

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • There was only one retrospective observational study reporting that adding long-acting GLP1 receptor agonist liraglutide to lifestyle measures, metformin and testosterone replacement therapy boosted erectile function in obese men with type 2 diabetes and different forms of hypogonadism.

    “There was only one retrospective observational study reporting that adding long-acting GLP1 receptor agonist liraglutide to LSM, metformin and TRT boosted erectile function in obese men with type 2 diabetes and different forms of hypogonadism (9).”

    From Effects of liraglutide on obesity-associated functional hypogonadism in men (2019) · cites this paper as [9]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Liraglutide groups did not reach the stated 7% glycaemic target

    Major

    The study defines the glycaemic target as HbA1c ≤7%, but the liraglutide-treated groups' T3 means are 7.3% (G1N) and 7.4% (G2N). The abstract's claim that adding liraglutide let them reach the target instead uses a different, <7.5% threshold.

  • G1N T2 LDL does not match the stated calculation

    Major

    Using the G1N T2 means, the stated formula gives 216.8 − (39.0 + 190.1/5) = 139.78 mg/dL, rather than the tabulated 133.6 mg/dL. Rounding of the printed means cannot explain this gap.

  • G2 T2 total cholesterol conflicts with its LDL value

    Minor

    Table 4 reports total cholesterol of 81.1 mg/dL and LDL cholesterol of 99.5 mg/dL at T2. Its stated LDL formula cannot produce an LDL value greater than total cholesterol when HDL and triglycerides are positive.

  • G2 baseline mean IIEF score violates the stated entry cutoff

    Minor

    The inclusion criterion requires every selected man's IIEF score to be below 14, yet the reported G2 baseline mean is 14.0. A mean of values all below 14 must itself be below 14.

  • HbA1c threshold switches from mmol/mol to nmol/mol

    Minor

    The abstract expresses the 58 HbA1c threshold in mmol/mol for the T2 result but in nmol/mol for the T3 target. Those units differ by a factor of one million.

  • Abstract says no patient reached the T2 glycaemic goal

    Minor

    The abstract says each patient remained above 7.5% HbA1c at T2, whereas Table 3 reports 7.0% for the G1Y patients at T2.

  • G2N baseline LDL does not match the stated calculation

    Minor

    The G2N baseline means give LDL = 189.9 − (35.7 + 319.1/5) = 90.38 mg/dL by the paper's formula, rather than the reported 105.6 mg/dL.

7 of 7

Cites

1 retracted

Flagged first, then by citations

Research works printed but not linked: 1

  1. Bourgeois FT, 2010, Adverse drug events in outpatient setting: and 11‐year national analysis Pharmacolepidemiol, Drug Saf, 19, 901

Cited by

Sorted by citations

Related

Authors
Giagulli, V. A., Carbone, M. D., Ramunni, M. I., Licchelli, B., De Pergola, G., Sabbà, C., Guastamacchia, E., & Triggiani, V.
Affiliations
  • University of Bari Aldo Moro (IT)
  • University of Foggia (IT)
  • Outpatient Clinic for Endocrinology and Metabolic Diseases Conversano Hospital Conversano Italy
  • Nutrition Outpatient Clinic Clinical Oncology Unit University of Bari Bari Italy
Corresponding author
Giagulli, V. A.
ORCID
Venue
Andrology
Publisher
Wiley
Published
2015-10-07
Volume
3
Issue
6
Pages
1094-1103
ISSN
  • 2047-2919 (ISSN-L)
  • 2047-2927
DOI
10.1111/andr.12099
OpenAlex
W1822586512
Semantic Scholar
25def00deb26b163e52d2bdb071051009529081c
Cited by
109
References
70
Citations by year
2026: 11 · 2025: 16 · 2024: 10 · 2023: 15 · 2022: 16 · 2021: 10 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 1 · 2016: 2 · 2015: 1
FWCI
3.78
Type
journal article
Language
en
Open access
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • Andrology (publishedVersion)
  • PubMed (publishedVersion)
  • CINECA IRIS Institutional Research Information System (University of Bari Aldo Moro) (submittedVersion, other-oa)
Topics
  • Health Sciences › Medicine › Psychiatry and Mental health › Sexual function and dysfunction studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal and reproductive studies
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
Keywords
liraglutide, erectile dysfunction, type 2 diabetes, obesity, hypogonadism, testosterone replacement therapy, metformin, lifestyle modification, glycemic control, HbA1c, sex hormone-binding globulin, Klinefelter syndrome, hypogonadotropic hypogonadism, GLP-1 receptor agonists
MeSH terms
Liraglutide, Blood Glucose, Diabetes Mellitus, Type 2, Drug Therapy, Combination, Glycated Hemoglobin, Humans, Hypoglycemic Agents, Hypogonadism, Erectile Dysfunction, Male, Metformin, Middle Aged, Obesity, Penile Erection, Retrospective Studies, Testosterone, Time Factors, Biomarkers, Weight Loss, Treatment Outcome, Hormone Replacement Therapy, Risk Reduction Behavior, Incretins

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-10.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-10.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

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