Effects of the glucagon-like peptide-1 receptor agonist dulaglutide on sexuality in healthy men: a randomised, double-blind, placebo-controlled crossover study.

BACKGROUND: The reward-regulatory properties of GLP-1 are attracting increasing interest. Animal studies show that GLP-1 receptor agonists not only reduce consumption of addictive substances, but also influence sexual behaviour. We aimed to investigate the effect of dulaglutide versus placebo on sexual desire in humans. METHODS: In this randomised, double-blind, placebo-controlled crossover trial, healthy eugonadal men of normal weight, aged 18-50 years with active and satisfactory sex lifes were (1:1) randomly allocated to dulaglutide or placebo for four weeks. We assessed sexual desire (Massachusetts General Hospital-Sexual Functioning Questionnaire [MGH-SFQ]), hormones of the hypothalamic-pituitary-gonadal axis (total testosterone, follicle-stimulating hormone [FSH], luteinizing hormone [LH]) and sperm parameters. Changes in these parameters were compared under dulaglutide versus placebo using paired t-tests. FINDINGS: 24 out of 26 randomised participants completed the study (13 participants randomised to dulaglutide first and 13 to placebo first). No change in the MGH-SFQ was observed after four weeks of dulaglutide versus placebo (estimated difference 0.58 [95% CI -0.83 to 2.00], p-value = 0.402). Hormones of the hypothalamic-pituitary-gonadal axis (estimated differences: total testosterone (nmol/l) 0.9 [95% CI -1.5 to 3.3], FSH (IU/l) -0.2 [95% CI -0.3 to 0.0] and LH (IU/l) -0.8 [95% CI -1.5 to 0.0]) as well as sperm parameters all remained in the normal range without significant differences between the treatments. No severe adverse events occurred. INTERPRETATION: In this study of healthy men, we found no evidence of negative impacts of a four-week treatment with the widely used GLP-1 receptor agonist dulaglutide on sexual desire, hypothalamic-pituitary-gonadal axis hormones or sperm parameters. FUNDING: Swiss National Science Foundation (PZ00P3_193206), Gottfried and Julia Bangerter-Rhyner Foundation, Goldschmidt-Jacobson Foundation, Swiss Academy of Medical Sciences.

Effects of dulaglutide on alcohol consumption during smoking cessation.

BACKGROUNDAlcohol use disorder has a detrimental impact on global health and new treatment targets are needed. Preclinical studies show attenuating effects of glucagon-like peptide-1 (GLP-1) agonists on addiction-related behaviors in rodents and nonhuman primates. Some trials have shown an effect of GLP-1 agonism on reward processes in humans; however, results from clinical studies remain inconclusive.METHODSThis is a predefined secondary analysis of a double-blind, randomized, placebo-controlled trial evaluating the GLP-1 agonist dulaglutide as a therapy for smoking cessation. The main objective was to assess differences in alcohol consumption after 12 weeks of treatment with dulaglutide compared to placebo. The effect of dulaglutide on alcohol consumption was analyzed using a multivariable generalized linear model.RESULTSIn the primary analysis, participants out of the cohort (n = 255) who reported drinking alcohol at baseline and who completed 12 weeks of treatment (n = 151; placebo n = 75, dulaglutide n = 76) were included. The median age was 42 (IQR 33-53) with 61% (n = 92) females. At week 12, participants receiving dulaglutide drank 29% less (relative effect = 0.71, 95% CI 0.52-0.97, P = 0.04) than participants receiving placebo. Changes in alcohol consumption were not correlated with smoking status at week 12.CONCLUSIONThese results provide evidence that dulaglutide reduces alcohol intake in humans and contribute to the growing body of literature promoting the use of GLP-1 agonists in treatment of substance use disorders.TRIAL REGISTRATIONClinicalTrials.gov NCT03204396.FUNDINGSwiss National Foundation, Gottfried Julia Bangerter-Rhyner Foundation, Goldschmidt-Jacobson Foundation, Hemmi Foundation, University of Basel, University Hospital Basel, Swiss Academy of Medical Science.

Assessment of diffuse transmission and reflection modes in near-infrared quantification, part 2: DIFFuse reflection information depth.

Near-infrared spectroscopy offers tremendous advantages for pharmaceutical manufacturing as a fast and nondestructive method of quantitative and qualitative analysis. Content uniformity (end-product analytics) and process analytics are two important applications of the method. Diffuse reflection (DR) information depth (vertical sampling span) assessment is of equal importance in content prediction applications and to understand the effect of inhomogeneities in the sample. Three experiments were conducted: (a) 0.5 to 10.0 mm incremental thickness MCC tablets with constant porosity, (b) MCC/phenylbutazone (PBZ) double-layered (DL) tablets (PBZ layer 0%-100% in 0.5 mm steps), and (c) Comparison of placebo and 30% caffeine tablet cores with incremental film coating (film thickness of 0-0.35 mm). Incremental thickness and cluster analysis of DL tablets showed that DR information depth was <0.5 mm, whereas the data fitting from incremental coating showed that signal drop reached 50% at 0.05 to 0.07 mm, depending on the wavenumber and 90% signal drop (10% information content) can be seen between 0.20 and 0.25 mm without extrapolation. These results mean that DR mode for pharmaceutical tablets obtains spectral information from the very surface, and radiation is barely reflected back from beyond thin-film coatings, making it less useful than diffuse transmission mode for core content analysis, especially for thick-coated, multilayer, multicore, or highly inhomogeneous tablets.