Aims/hypothesis Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that has been demonstrated to successfully treat diabetes and promote weight loss. The mechanisms by which liraglutide confers weight loss remain to be fully clarified. Thus, we investigated whether GLP-1 receptors are expressed in human brains and whether liraglutide administration affects neural responses to food cues in diabetic individuals (primary outcome). Methods In 22 consecutively studied human brains, expression of GLP-1 receptors in the hypothalamus, medulla oblongata and parietal cortex was examined using immunohistochemistry. In a randomised (assigned by the pharmacy using a randomisation enrollment table), placebo-controlled, double-blind, crossover trial, 21 individuals with type 2 diabetes (18 included in analysis due to lack or poor quality of data) were treated with placebo and liraglutide for a total of 17 days each (0.6 mg for 7 days, 1.2 mg for 7 days and 1.8 mg for 3 days). Participants were eligible if they had type 2 diabetes and were currently being treated with lifestyle changes or metformin. Participants, caregivers, people doing measurements and/or examinations, and people assessing the outcomes were blinded to the medication assignment. We studied metabolic changes as well as neurocognitive and neuroimaging (fMRI) of responses to food cues at the clinical research centre of Beth Israel Deaconess Medical Center. Results Immunohistochemical analysis revealed the presence of GLP-1 receptors on neurons in the human hypothalamus, medulla and parietal cortex. Liraglutide decreased activation of the parietal cortex in response to highly desirable (vs less desirable) food images (p < 0.001; effect size: placebo 0.53 ± 0.24, liraglutide −0.47 ± 0.18). No significant adverse effects were noted. In a secondary analysis, we observed decreased activation in the insula and putamen, areas involved in the reward system. Furthermore, we showed that increased ratings of hunger and appetite correlated with increased brain activation in response to highly desirable food cues while on liraglutide, while ratings of nausea correlated with decreased brain activation. Conclusions/interpretation For the first time, we demonstrate the presence of GLP-1 receptors in human brains. We also observe that liraglutide alters brain activity related to highly desirable food cues. Our data point to a central mechanism contributing to, or underlying, the effects of liraglutide on metabolism and weight loss. Future studies will be needed to confirm and extend these findings in larger samples of diabetic individuals and/or with the higher doses of liraglutide (3 mg) recently approved for obesity.

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Objectives. To examine indoor tanning trends among US adults, and the relation to indoor tanning youth access legislation. Methods. This study analyzed the Health Information National Trends Survey (HINTS), a mailed survey, from the years 2007, 2011, 2013, 2014, 2017, and 2018 (combined n = 20 2019). Results. Indoor tanning prevalence decreased significantly over time among all US adults from 2007 (10%) to 2018 (4%; P < .001), among young adults aged 18 to 34 years (14% to 4%; P < .001), and among both women (14% to 4%; P < .001) and men (5% to 4%; P < .05). Indoor tanning significantly decreased in states that enacted youth access legislation by 2018, but did not significantly decrease for other states. Frequent indoor tanning was common in 2018; about one quarter of respondents who reported any indoor tanning did so 25 times or more in the past year. Conclusions. This study identifies several challenges in continuing to reduce indoor tanning in the United States. Youth access legislation may be effective for reducing tanning among the broader population of tanners; however, there remains a need for focus on highly frequent tanners, as well as men.