Effects of liraglutide on diastolic function parameters in patients with type 2 diabetes and coronary artery disease: a randomized crossover study.

BACKGROUND: Diastolic dysfunction is highly prevalent in patients with type 2 diabetes mellitus (T2DM) and is associated with overweight, glucose dysregulation and coronary artery disease (CAD). The GLP-1 receptor agonist, liraglutide, has shown to induce weight loss and improve metabolic factors, thus modulating factors associated with diastolic dysfunction. We have previously reported the effects of liraglutide on systolic function, and in this current study we explore the effects of liraglutide on diastolic function parameters in patients with stable CAD, preserved left ventricular ejection fraction (LVEF), and newly diagnosed T2DM. METHODS: Thirty subjects were randomized to liraglutide or placebo intervention for 12 + 12-weeks in this double-blind cross-over study. 2D-echocardiography using tissue velocity imaging was used for assessment of diastolic function parameters. Early diastolic filling velocity (E), late atrial filling velocity (A), E-wave deceleration time (EDT) and E/A ratio was assessed from the pulse wave (PW)-Doppler velocity recording of the mitral inflow. Peak early diastolic annular velocities (e') was measured from color tissue doppler images. RESULTS: Liraglutide, when compared to placebo, induced a significant reduction in average e' and lateral e' velocities (- 0.57 cm/s [- 1.05 to - 0.08] and -0.74 cm/s [-1.32 to -0.15], respectively). Adjusted for the concomitant increase in HR (+ 6.16 bpm [0.79 to 11.54], the changes were not significant. No significant changes in other diastolic function parameters were observed. CONCLUSIONS: Liraglutide therapy did not improve any diastolic function parameters in subjects with T2DM, CAD, and preserved LVEF. Instead, a deterioration in e' was observed, which was associated to an increase in heart rate induced by liraglutide therapy. Trial registration Clinical Trial Registration: http://www.clinicaltrials.gov (unique identifier: NCT01595789) (first submitted May 8, 2012).

Effects of 1 year of exercise training versus combined exercise training and weight loss on body composition, low-grade inflammation and lipids in overweight patients with coronary artery disease: a randomized trial.

BACKGROUND: Dyslipidaemia and low-grade inflammation are central in atherogenesis and linked to overweight and physical inactivity. Lifestyle changes are important in secondary prevention of coronary artery disease (CAD). We compared the effects of combined weight loss and interval training with interval training alone on physical fitness, body composition, dyslipidaemia and low-grade inflammation in overweight, sedentary participants with CAD. METHODS: Seventy CAD patients, BMI 28-40 kg/m2 and age 45-75 years were randomised to (1) 12 weeks' aerobic interval training (AIT) at 90% of peak heart rate three times/week followed by 40 weeks' AIT twice weekly or (2) a low energy diet (LED) (800-1000 kcal/day) for 8-10 weeks followed by 40 weeks' weight maintenance including AIT twice weekly and a high-protein/low-glycaemic load diet. Effects of the intervention were evaluated by physical fitness, body weight and composition. Dyslipidaemia was described using both biochemical analysis of lipid concentrations and lipoprotein particle subclass distribution determined by density profiling. Low-grade inflammation was determined by C-reactive protein, soluble urokinase-type plasminogen activator receptor and tumour necrosis factor α. Effects on continuous outcomes were tested by mixed-models analysis. RESULTS: Twenty-six (74%) AIT and 29 (83%) LED + AIT participants completed the study. At baseline subject included 43 (78%) men; subjects averages were: age 63 years (6.2), body weight 95.9 kg (12.2) and VO2peak 20.7 mL O2/kg/min (4.9). Forty-six (84%) had pre-diabetes (i.e. impaired fasting glucose and/or impaired glucose tolerance). LED + AIT reduced body weight by 7.2 kg (- 8.4; - 6.1) and waist circumference by 6.6 cm (- 7.7; - 5.5) compared to 1.7 kg (- 0.7; - 2.6) and 3.3 cm (- 5.1; - 1.5) after AIT (within-group p < 0.001, between-group p < 0.001 and p = 0.018, respectively). Treatments caused similar changes in VO2peak and lowering of total cholesterol, triglycerides, non-HDL cholesterol and low-grade inflammation. A shift toward larger HDL particles was seen following LED + AIT while AIT elicited no change. CONCLUSIONS: Both interventions were feasible. Both groups obtained improvements in VO2peak, serum-lipids and inflammation with superior weight loss and greater central fat loss following LED + AIT. Combined LED induced weight loss and exercise can be recommended to CAD patients. Trial registration NCT01724567, November 12, 2012, retrospectively registered (enrolment ended in April 2013).

Liraglutide in combination with metformin may improve the atherogenic lipid profile and decrease C-reactive protein level in statin treated obese patients with coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.

BACKGROUND AND AIMS: Atherosclerosis in obesity and type 2 diabetes (T2DM) is associated with low-grade inflammation (LGI) and dyslipidemia, where especially small, dense lipoprotein particles are atherogenic. The glucagon-like peptide-1 receptor agonist, liraglutide, reduces cardiovascular events by poorly understood mechanisms. We investigated the effect of liraglutide combined with metformin on LGI and lipoprotein density profiles in patients with stable coronary artery disease (CAD) and newly diagnosed T2DM. METHODS: We conducted a randomized, double-blind, placebo-controlled, cross-over trial over a 12 + 12-week period, with ≥2-week wash-out. INTERVENTION: liraglutide/metformin vs. placebo/metformin. Lipoproteins were separated by continuous density gradient ultracentrifugation, and LDL divided into five subfractions between 226 and 270 Å, considering particle size ≤255 Šas the atherogenic pattern. Plasma C-reactive protein and tumor necrosis factor-α were assessed by the enzyme-linked immunosorbent-assay. RESULTS: 28 out of 41 randomized patients completed all visits. Intention-to-treat analysis was performed but one patient had statin dosage and was excluded from the analysis. 95% of the patients were on statin therapy. Overall, liraglutide did not affect lipid subfractions or markers of LGI compared to placebo. The combination of liraglutide and metformin reduced the total LDL subfractions, primarily by reducing the most atherogenic subfraction LDL5, and reduced CRP but not TNF-α. Explorative analyses suggested that the subfraction LDL5 during the wash-out period rebounded significantly at least in a per-protocol analysis of the sub-group of patients starting the liraglutide therapy. CONCLUSIONS: In patients with CAD and newly diagnosed T2DM on stable statin therapy, liraglutide combined with metformin may improve the atherogenic LDL lipid profile and CRP.

Liraglutide improves the beta-cell function without increasing insulin secretion during a mixed meal in patients, who exhibit well-controlled type 2 diabetes and coronary artery disease.

BACKGROUND: Hyperinsulinemia aggravates insulin resistance and cardio-vascular disease. How the insulinotropic glucagon-like peptide-1 receptor agonist liraglutide in a physiologic post-prandial setting may act on pancreatic alpha and beta-cell function in patients with coronary artery disease (CAD) and type 2 diabetes (T2DM) is less clear. METHODS: Insulin resistant patients with established CAD and newly diagnosed well-controlled T2DM were recruited to a placebo-controlled, cross-over trial with two treatment periods of 12 weeks and a 2 weeks wash-out period before and in-between. Treatment was liraglutide or placebo titrated from 0.6 mg q.d. to 1.8 mg q.d. within 4 weeks and metformin titrated from 500 mg b.i.d to 1000 mg b.i.d. within 4 weeks. Before and after intervention in both 12 weeks periods insulin, C-peptide, glucose, and glucagon were measured during a meal test. Beta-cell function derived from the oral glucose tolerance setting was calculated as changes in insulin secretion per unit changes in glucose concentration (Btotal) and whole-body insulin resistance using ISIcomposite. RESULTS: Liraglutide increased the disposition index [Btotal × ISIcomposite, by 40% (n = 24, p < 0.001)] compared to placebo. Post-prandial insulin and glucose was reduced by metformin in combination with liraglutide and differed, but not significantly different from placebo, moreover, glucagon concentration was unaffected. Additionally, insulin clearance tended to increase during liraglutide therapy (n = 26, p = 0.06). CONCLUSIONS: The insulinotropic drug liraglutide may without increasing the insulin concentration reduce postprandial glucose but not glucagon excursions and improve beta-cell function in newly diagnosed and well-controlled T2DM.Trial registration Clinicaltrials.gov ID: NCT01595789.

Effect of liraglutide on estimates of lipolysis and lipid oxidation in obese patients with stable coronary artery disease and newly diagnosed type 2 diabetes: A randomized trial.

Elevated levels of non-esterified fatty acids (NEFA) play a role in insulin resistance, impaired beta-cell function and they are a denominator of the abnormal atherogenic lipid profile that characterizes obese patients with type 2 diabetes (T2DM). We hypothesized that the GLP-1 receptor agonist liraglutide, in combination with metformin, would reduce lipolysis. In a randomized, double-blind, placebo-controlled, cross-over trial, 41 T2DM patients with coronary artery disease were randomized and treated with liraglutide-metformin vs placebo-metformin during 12- + 12-week periods with a wash-out period of at least 2 weeks before and between the intervention periods. NEFA kinetics were estimated using the Boston Minimal Model of NEFA metabolism, with plasma NEFA and glucose levels measured during a standard 180-minute frequently sampled intravenous glucose tolerance test. Liraglutide-metformin reduced estimates of lipolysis. Furthermore, placebo-metformin increased estimates of lipid oxidation, while treatment with liraglutide eliminated this effect. We conclude that liraglutide exerts a clinically relevant reduction in estimates of lipolysis and lipid oxidation which is explained, in part, by improved insulin secretion, as revealed by an intravenous glucose tolerance test.

The acute effects of dietary carbohydrate reduction on postprandial responses of non-esterified fatty acids and triglycerides: a randomized trial.

BACKGROUND: Postprandial non-esterified fatty acid (NEFA) and triglyceride (TG) responses are increased in subjects with type 2 diabetes mellitus (T2DM) and may impair insulin action and increase risk of cardiovascular disease and death. Dietary carbohydrate reduction has been suggested as non-pharmacological therapy for T2DM, but the acute effects on NEFA and TG during subsequent meals remain to be investigated. METHODS: Postprandial NEFA and TG responses were assessed in subjects with T2DM by comparing a carbohydrate-reduced high-protein (CRHP) diet with a conventional diabetes (CD) diet in an open-label, randomized, cross-over study. Each diet was consumed on two consecutive days, separated by a wash-out period. The iso-caloric CRHP/CD diets contained 31/54 E% from carbohydrate, 29/16 E% energy from protein and 40/30 E% from fat, respectively. Sixteen subjects with well-controlled T2DM (median HbA1c 47 mmol/mol, (37-67 mmol/mol) and BMI 30 ± 4.4 kg/m2) participated in the study. NEFA and TG were evaluated following breakfast and lunch. RESULTS: NEFA net area under curve (AUC) was increased by 97 ± 38 µmol/Lx270 min (p = 0.024) after breakfast but reduced by 141 ± 33 µmol/Lx180 min (p < 0.001) after lunch on the CRHP compared with CD diet. Likewise, TG net AUC was increased by 80 ± 28 µmol/Lx270 min (p = 0.012) after breakfast but reduced by 320 ± 60 µmol/Lx180 min (p < 0.001) after lunch on the CRHP compared with CD diet. CONCLUSIONS: In well-controlled T2DM a modest reduction of dietary carbohydrate with a corresponding increase in protein and fat acutely reduced postprandial serum NEFA suppression and increased serum TG responses after a breakfast meal but had the opposite effect after a lunch meal. The mechanism behind this second-meal phenomenon of CRHP diet on important risk factors for aggravating T2DM and cardiovascular disease awaits further investigation. TRIAL REGISTRATION: The study was registered at clinicaltrials.gov ID: NCT02472951. https://clinicaltrials.gov/ct2/show/NCT02472951 . Registered June 16, 2015.

Liraglutide effects on beta-cell, insulin sensitivity and glucose effectiveness in patients with stable coronary artery disease and newly diagnosed type 2 diabetes.

AIMS: The aims of the study were to investigate the effects of the GLP-1 receptor agonist liraglutide as add-on to metformin on insulin sensitivity (Si) and glucose effectiveness (Sg) in addition to its positive effects on beta-cell function in overweight/obese patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). METHODS: The design of the study was a randomized, double-blind, placebo-controlled, cross-over trial in patients with stable CAD and newly diagnosed well-controlled T2DM. Patients were treated with liraglutide/metformin vs placebo/metformin for a 12 + 12-week period with ≥2-week wash-out. First phase insulin secretion (AIRg), Si and Sg were estimated by the Bergman Minimal Model, enabling calculation of beta-cell function; Disposition Index (DI) = AIRg × Si. A total of 30 patients from among 41 randomized were available for paired analysis. RESULTS: Baseline characteristics were: HbA1c 47 mmol/mol (SD 6), BMI 31.6 kg/m2 (SD 4.8), fasting plasma-glucose 6.9 mmol/L (IQR 6.1; 7.4) and HOMA-IR 4.9 (IQR 3.0; 7.5). Liraglutide treatment improved AIRg by 3-fold, 497 mU × L-1 × min (IQR 342; 626, P < .0001) and DI by 1-fold, 766 (SD 824, P < .0001). Despite a significant weight loss of -2.7 kg (-6.7; -0.6) during liraglutide treatment, we found no improvement in HOMA-IR, Si or Sg. Weight loss during liraglutide therapy did not result in a carry-over effect. CONCLUSION: Liraglutide as add-on to metformin induces a clinically significant improvement in beta-cell function in overweight/obese, high cardiovascular risk patients with newly diagnosed well-controlled T2DM and CAD. The effect of liraglutide on DI is mediated entirely by improved AIRg whereas the effects on Si and Sg are neutral.

Effects of the glucagon-like peptide-1 receptor agonist liraglutide on 24-h ambulatory blood pressure in patients with type 2 diabetes and stable coronary artery disease: a randomized, double-blind, placebo-controlled, crossover study.

OBJECTIVE: The glucagon-like peptide-1 receptor agonist liraglutide has been shown to reduce blood pressure (BP) in clinical trials using office BP measurements. However, the effects of liraglutide on 24-h BP and on the diurnal variation in BP have not been explored sufficiently. METHODS: Forty-one patients with type 2 diabetes and stable coronary artery disease were randomized to receive liraglutide or placebo to a backbone therapy of metformin in this double-blind, placebo-controlled 12 along with 12 weeks crossover study. Ambulatory blood pressure monitoring (ABPM) was performed at the start and end of each intervention. RESULTS: Twenty-four individuals completed all 24-h BP measurements. Liraglutide, when compared with placebo, did not induce any significant changes in mean 24-h SBP [difference +1.8 mmHg (95% confidence interval, 95% CI: -4.33 to 7.93)] or DBP [+4.2 mmHg (-0.74 to 9.17)]. Twenty-four-hour BP profiles revealed a trend for increase in evening SBP and DBP [+9.2 mmHg (95% CI: 1.1-17.2) and +9.7 mmHg (95% CI: 3.9-15.5), respectively]. Mean heart rate significantly increased after liraglutide [+7.6 bpm (95% CI: 2.56-12.62)]. Liraglutide did not affect the BP variability or the nocturnal BP dipping. CONCLUSIONS: We could not demonstrate any BP-lowering effect of liraglutide when using 24-h ABPM. Liraglutide exhibited diurnal variation in the effect on BP without affecting the BP variability or nocturnal BP dipping.

Effects of Liraglutide on Heart Rate and Heart Rate Variability: A Randomized, Double-Blind, Placebo-Controlled Crossover Study.

OBJECTIVE: Reduced heart rate variability (HRV) and increased heart rate (HR) have been associated with cardiovascular mortality. Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) increase HR, and studies have suggested that they may reduce HRV. We examined the effect of the GLP-1 RA liraglutide on HRV and diurnal variation of HR in overweight patients with newly diagnosed type 2 diabetes (T2D) and stable coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: Liraglutide or placebo was administrated to a backbone therapy of metformin in this double-blind, placebo-controlled 12 + 12-week crossover study. SD of beat-to-beat (NN) intervals (SDNN) was assessed by 24-h Holter monitoring as a measure of HRV. Diurnal HR variation and sympathovagal balance analyzed by root mean square of successive differences (RMSSD) in NN intervals and high-frequency (HF) and low-frequency (LF) power were assessed. RESULTS: Compared with placebo, liraglutide decreased SDNN in 27 subjects (-33.9 ms; P < 0.001, paired analysis); decreased RMSSD (-0.3 log-ms; P = 0.025); and increased the mean HR (8.1 beats/min; P = 0.003), daytime HR (5.7; P = 0.083), and nighttime HR (6.3; P = 0.026). In a multivariable regression analysis, the decrease in SDNN remained significant after adjustment for metabolic and HR changes. Liraglutide reduced HF power (-0.7 log-ms2; P = 0.026) without any change in LF/HF ratio. CONCLUSIONS: In overweight patients with CAD and newly diagnosed T2D, liraglutide increased HR and reduced HRV despite significant weight loss and improvement in metabolic parameters. The increase in nightly HR in conjunction with a decrease in parameters of parasympathetic activity suggests that liraglutide may affect sympathovagal balance.

Effects of the glucagon-like peptide-1 receptor agonist liraglutide on systolic function in patients with coronary artery disease and type 2 diabetes: a randomized double-blind placebo-controlled crossover study.

BACKGROUND: Patients with type 2 diabetes (T2D) and coronary artery disease (CAD) have increased risk of cardiac dysfunction. The diabetic heart is characterized by increased fatty acid oxidation and reduced glucose uptake resulting in reduced cardiac efficiency. Glucagon-like peptide-1 (GLP-1) has shown to increase myocardial glucose uptake and to improve myocardial function. We examined the effect of the GLP-1 receptor agonist, liraglutide, on the systolic function of the left ventricle (LV) in patients with T2D and stable CAD. METHODS: In this placebo-controlled crossover study, 41 subjects with T2D and stable CAD were randomized to liraglutide or placebo and underwent dobutamine stress echocardiography (DSE) and exercise tolerance test at beginning and end of each intervention. The primary endpoint was changes in LV ejection fraction. Secondary endpoints were exercise capacity and other measures of systolic function: wall motion score index (WMSI), global longitudinal strain (GLS) and strain rate (GLSR). RESULTS: Liraglutide, when compared to placebo, did not improve LV ejection fraction at rest (+0.54 %; 95 % CI 2.38-3.45), at low stress (+0.03 %; 95 % CI 3.25-3.32), at peak stress (+1.12 %; 95 % CI 3.45-5.69), or at recovery (+4.06 %; 95 % CI 0.81-8.93). No significant changes in WMSI were observed at any stress levels. GLS and GLSR at rest did not improve. The maximal exercise capacity estimated by metabolic equivalents was not affected by liraglutide. CONCLUSION: In conclusion, liraglutide did not improve the systolic function of the left ventricle during DSE or the exercise capacity in patients with T2D and stable CAD. Clinical Trial Registration http://www.clinicaltrials.gov (unique identifier: NCT01595789).

Weight loss is superior to exercise in improving the atherogenic lipid profile in a sedentary, overweight population with stable coronary artery disease: A randomized trial.

BACKGROUND: Dyslipidemia and low-grade inflammation are integral in the pathogenesis of atherosclerosis. We aim to compare the effects of a considerable weight loss and intensive exercise training on lipid atherogenicity and low-grade inflammation in a high-risk population with coronary artery disease (CAD). METHODS: Seventy non-diabetic participants with CAD, BMI 28-40 kg/m(2), age 45-75 years were randomized to 12 weeks' aerobic interval training (AIT) at 85-90% of peak heart rate three times/week or a low energy diet (LED, 800-1000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight maintenance diet. Lipid profile atherogenicity was described using lipoprotein particle size and density profiling. Low-grade inflammation was evaluated by tumor necrosis factor alpha (TNFα), C-reactive protein, interleukin 6 and soluble urokinase plasminogen activator receptor. RESULTS: Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. AIT and LED decreased total (AIT: -518 {-906;-129},P = 0.011, LED: -767 {-1128:-406},P < 0.001) and low-density lipoprotein (LDL, AIT: -186 {-306;-65},P = 0.004, LED: -277 {-433;-122},P < 0.001) assessed as the area under the density profile curve. LED was superior to AIT in decreasing atherogenicity reflected by increased LDL (between-group: 1.0 Å {0.4; 1.7},P = 0.003) and high-density lipoprotein (between-group: 1.2 Å {0.2; 2.4},P = 0.026) particle size and a decreased proportion of total lipoprotein constituted by the small, dense LDL5 subfraction (between-group: -5.0% {-8.4;-1.7},P = 0.004). LED decreased TNFα (9.5% {-15.8;-2.6},P = 0.009). No changes were seen following AIT. CONCLUSION: LED and AIT decreased total and LDL lipoprotein. LED was superior in decreasing atherogenicity assessed by a shift in density profile and increased particle size. Effect on low-grade inflammation was limited.

A randomized trial comparing the effect of weight loss and exercise training on insulin sensitivity and glucose metabolism in coronary artery disease.

AIM: The majority of patients with coronary artery disease (CAD) exhibit abnormal glucose metabolism, which is associated with mortality even at non-diabetic glucose levels. This trial aims to compare the effects of a considerable weight loss and exercise with limited weight loss on glucose metabolism in prediabetic, CAD patients. METHODS AND RESULTS: Seventy non-diabetic participants with CAD, BMI 28-40 kg/m(2), age 45-75 years were randomized to 12 weeks' aerobic interval training (AIT) at 90% peak heart rate three times weekly or a low energy diet (LED, 800-1,000 kcal/day) for 8-10 weeks followed by 2-4 weeks' weight maintenance diet. Glucose tolerance, insulin action, ß-cell function and suppression of lipolysis were assessed using a 3-h oral glucose tolerance test. ISI-composite and ISI-HOMA (=1/HOMA-IR) were calculated as surrogate measures of whole-body and hepatic insulin sensitivity, respectively. Magnetic resonance imaging estimated abdominal adipose tissue. Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. LED increased ISI-composite by 55% and ISI-HOMA by 70% (p<0.01) while AIT did not change insulin sensitivity (p>0.7) revealing a significant difference between the groups (p<0.05). No concurrent significant changes in lipolysis, ß-cell responsiveness or insulin clearance were seen. Changes in ISI-HOMA and ISI-composite were associated with reduced visceral abdominal fat, waist circumference and body weight. Intention-to-treat analyses (n=64) yielded similar results. CONCLUSION: LED is superior to AIT in improving insulin sensitivity in prediabetic CAD patients. Changes in insulin sensitivity are associated with decreased visceral abdominal fat, waist circumference and body weight.

Adding liraglutide to the backbone therapy of biguanide in patients with coronary artery disease and newly diagnosed type-2 diabetes (the AddHope2 study): a randomised controlled study protocol.

INTRODUCTION: Newly diagnosed type 2 diabetes mellitus (T2DM) in patients with coronary artery disease (CAD) more than doubles the risk of death compared with otherwise matched glucose tolerant patients. The biguanide metformin is the drug of choice in treatment of T2DM and has shown to ameliorate cardiovascular morbidity in patients with T2DM and myocardial infarction (MI). The incretin hormone, glucagon-like peptide-1 (GLP-1) improves ß-cell function, insulin sensitivity and causes weight loss and has been suggested to have beneficial effects on cardiac function. The GLP-1 receptor agonist (GLP-1RA), liraglutide, is currently used for treatment of T2DM but its potential effect on cardiac function has not been investigated in detail. We hypothesised that liraglutide added to metformin backbone therapy in patients with CAD and newly diagnosed T2DM will improve ß-cell function and left ventricular systolic function during dobutamine stress. METHODS AND ANALYSES: 40 patients with CAD and newly diagnosed T2DM will receive the intervention liraglutide+metformin and placebo+metformin in this investigator-initiated, double blind, randomised, placebo-controlled, cross-over 12 plus 12 weeks intervention study with a 2-week washout period. The primary cardiovascular end point is changes in left ventricular ejection fraction during stress echocardiography. The primary endocrine end point is ß-cell function evaluated during a frequently sampled intravenous glucose tolerance test. Secondary end points include heart rate variability, diurnal blood pressure, glucagon suppression and inflammatory response (urine, blood and adipose tissue). ETHICS AND DISSEMINATION: This study is approved by the Danish Medicines Agency, the Danish Dataprotection Agency and the Regional Committee on Biomedical Research Ethics of the Capital Region of Denmark. The trial will be carried out under the guidance from the GCP unit at Copenhagen University Hospital of Bispebjerg and in accordance with the ICH-GCP guidelines and the Helsinki Declaration. TRIAL REGISTRATIONS NUMBER: Clinicaltrials.gov ID: NCT01595789, EudraCT: 2011-005405-78.

[Hyperprolactin as cause of hypoactive sexual desire in men]. / Hyperprolaktinæmi som årsag til nedsat sexlyst hos mænd.

Algorithms previously focused primarily on the testosterone level and its role when diagnosing and managing hypoactive sexual desire (HSD) in men. The importance of prolactin in male sexuality is recognized and should be taken into account when investigating more complex cases of HSD in men.