-In-this-posthoc-study-an-investigation-was-carried-out-on-the-effect-of-liraglutide-on-CVDrisk-associated-ceramides-in-two-randomized-clinical-trials-including-participants-with-type-2-diabetes-T2D-s

METHODS: This study analyzed plasma samples from two independent randomized placebo-controlled clinical trials. The first trial, Antiproteinuric Effects of Liraglutide Treatment (LirAlbu12) followed a crossover design where 27 participants were treated for 12 weeks with either liraglutide (1 mg/d) or placebo, followed by a four-week washout period, and then another 12 weeks of the other treatment. The second clinical trial, Effect of Liraglutide on Vascular Inflammation in Type-2 Diabetes (LiraFlame26), lasted for 26 weeks and followed a parallel design, where 102 participants were randomized 1:1 to either liraglutide or placebo. Heresix prespecified plasma ceramides were measured using liquid chromatography mass spectrometry and assessed their changes using linear mixed models. Possible confounders were assessed with mediation analyses.RESULTS: In the LiraFlame26 trial, 26-week treatment with liraglutide resulted in a significant reduction of two ceramides associated with CVD risk, C16 Cer and C24:1 Cer (p < 05) compared to placebo.

None of the remaining ceramides showed statistically significant changes in response to liraglutide treatment compared to placebo. glipizide drug class in ceramides were not found after 12-weeks of liraglutide treatment in the LirAlbu12 trial. Mediation analyses showed that weight loss did not affect ceramide reduction.CONCLUSIONS: It was demonstrated that treatment with liraglutide resulted in a reduction in C16 Cer and C24:1 Cer after 26 weeks of treatment. These findings suggest the GLP-1RA can be used to modulate ceramides in addition to its other TRIAL REGISTRATION: Clinicaltrial.gov identifier: NCT02545738 and NCT03449654.Conflict of interest statement: The authors declare no conflict of interest compromising the integrity of this work.

Disclosures outside this work: EZ and BJvS are now employees at Novo Nordisk and have shares in Novo Nordisk. RR has served as consultant for Novo Nordisk and has shares in Novo Nordisk. AK has served on advisory boards or as consultant for Novo Nordisk, Curium, Clarity Pharmaceuticals, IPSEN, and Siemens Healthineers. TH own shares in Novo Nordisk. TV has served on scientific advisory panels, been part of speaker's bureaus, served as a consultant to and/or received research support from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Gilead, GSK, Mundipharma, Novo Nordisk, Sanofi and Sun Pharmaceuticals. PR has received honoraria for consultancy to Steno Diabetes Center Copenhagen from Astellas, Astra Zeneca, Boehringer Ingelheim, Bayer, Merck, Gilead, Novo Nordisk, Sanofi Aventis. CLQ has served on scientific advisory panels and/or received research support from Pfizer, Novo Nordisk and other companies via the IMI funding scheme.

Effect of GLP-1 Receptor Agonists in the Cardiometabolic Complications in a Rat Mississippi Medical Center, Jackson, Mississippi.Polycystic ovary syndrome (PCOS) is characterized by hyperandrogenism and ovulatory dysfunction. Women with PCOS have an elevated prevalence of cardiometabolic risk factors that worsen after menopause. Liraglutide (Lira), a glucagon-like peptide-1 receptor agonist, has shown beneficial metabolic effects in small clinic trials in reproductive-age women with PCOS. We have shown that chronic hyperandrogenemia in an experimental model of postmenopausal PCOS is associated with an adverse cardiometabolic profile and upregulation of the intrarenal renin-angiotensin system (RAS). We analyzed the effect of Lira in the cardiometabolic profile, intrarenal RAS, and blood pressure (BP) in postmenopausal PCOS. Four-week-old female Sprague Dawley rats were treated with DHT or placebo for 17 months.

Lira administration during the last 3 weeks caused a bigger reduction in food intake, body weight, fat mass, and homeostasis model assessment of insulin resistance index in PCOS than in control rats. Moreover, Lira improved dyslipidemia and elevated leptin levels in PCOS. In contrast, Lira decreased intrarenal expression of RAS components only in the control group. Lira transiently increased heart rate and decreased BP in control rats. However, glipizide drug class did not modify BP but increased heart rate in PCOS. The angiotensin-converting-enzyme inhibitor enalapril abolished the BP differences between PCOS and control rats. However, Lira coadministration with enalapril further reduced BP only in control rats.

In summary, Lira has beneficial effects for several cardiometabolic risk factors in postmenopausal PCOS. However, hyperandrogenemia blunted the BP-lowering effect of Lira in postmenopausal PCOS. Androgen-induced activation of intrarenal RAS may play a major role mediating increases in BP in postmenopausal PCOS.Intensive Behavioral Therapy for Obesity Combined with Liraglutide 3 mg: A School of Medicine at the University of Pennsylvania, Philadelphia, Philadelphia, Philadelphia, Pennsylvania, USA.School of Nursing, Philadelphia, Pennsylvania, USA.Pennsylvania, Philadelphia, Pennsylvania, USA.OBJECTIVE: The Centers for Medicare and Medicaid Services (CMS) covers intensive behavioral therapy (IBT) for obesity.