Browsing by Subject "RECEPTOR AGONISTS"

Sort by: Order: Results:

Now showing items 1-3 of 3
  • Jarvinen, Anna; Laine, Merja K.; Tikkanen, Roope; Castren, Maija L. (2019)
    Individuals with autism spectrum disorder (ASD) frequently display intensely repetitive, restricted thoughts, and behaviors. These behaviors have similarities to compulsions and/ or obsessions in obsessive compulsive disorder (OCD) and are primarily treated with behaviourally-based interventions and serotonin uptake inhibitors (SSRIs). Due to the lack of treatment responses in many cases, however, new treatments are being sought. Here we report beneficial effects of treatment with liraglutide, a glucagon-like peptide-1 (GLP-1) analog, on severe obsessive food craving, binge eating, weight gain, and behavioral problems in an adolescent male with infantile autism and moderate intellectual impairment. Liraglutide treatment reduced weight and unwanted behavior seemingly by preventing food-related repetitive thoughts and compulsions. Our report provides clinical evidence that GLP-1 signaling pathway may represent a novel target for treating food-related behavioral problems and aggressive behavior in ASD.
  • Matikainen, Niina; Söderlund, Sanni; Björnson, Elias; Pietiläinen, Kirsi; Hakkarainen, Antti; Lundbom, Nina; Taskinen, Marja-Riitta; Boren, Jan (2019)
    Aims Patients with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD) exhibit considerable residual risk for cardiovascular disease (CVD). There is, therefore, increasing interest in targeting postprandial lipid metabolism and remnant cholesterol. Treatment with the glucagon-like peptide 1 (GLP-1) analogue liraglutide reduces CVD risk by mechanisms that remain unexplained in part. Here we investigated the effects of liraglutide intervention on ectopic fat depots, hepatic lipogenesis and fat oxidation, postprandial lipid metabolism and glycaemia in humans with type 2 diabetes. Methods The effect of liraglutide was investigated in 22 patients with adequately controlled type 2 diabetes. Patients were randomly allocated, in a single-blind fashion, to either liraglutide 1.8 mg or placebo once daily for 16 weeks. Because liraglutide is known to promote weight loss, the study included dietary counselling to achieve similar weight loss in the liraglutide and placebo groups. Cardiometabolic responses to a high-fat mixed meal were measured before and at the end of the liraglutide intervention. Results Weight loss at Week 16 was similar between the groups: -2.4 kg (-2.5%) in the liraglutide group and -2.1 kg (-2.2%) in the placebo group. HBA1c improved by 6.4 mmol/mol (0.6%) in the liraglutide group (P = 0.005). Liver fat decreased in both groups, by 31% in the liraglutide group and by 18% in the placebo group, but there were no significant changes in the rate of hepatic de novo lipogenesis or beta-hydroxybutyrate levels, a marker of fat oxidation. We observed significant postprandial decreases in triglycerides only in plasma, chylomicrons and VLDL, and remnant particle cholesterol after treatment in the liraglutide group. Fasting and postprandial apoCIII concentrations decreased after liraglutide intervention and these changes were closely related to reduced glycaemia. In relative importance analysis, approximately half of the changes in postprandial lipids were explained by reductions in apoCIII concentrations, whereas less than 10% of the variation in postprandial lipids was explained by reductions in weight, glycaemic control, liver fat or postprandial insulin responses. Conclusions Intervention with liraglutide for 16 weeks produces multiple improvements in cardiometabolic risk factors that were not seen in the placebo group, despite similar weight loss. Of particular importance was a marked reduction in postprandial atherogenic remnant particles. The underlying mechanism may be improved glycaemic control, which leads to reduced expression of apoCIII, a key regulator of hypertriglyceridaemia in hyperglycaemic patients.
  • Nauck, Michael A.; McGuire, Darren K.; Pieper, Karen S.; Lokhnygina, Yuliya; Strandberg, Timo E.; Riefflin, Axel; Delibasi, Tuncay; Peterson, Eric D.; White, Harvey D.; Scott, Russell; Holman, Rury R. (2019)
    Background To examine the effects of the DPP-4i sitagliptin on CV outcomes during and after incident MI in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin (TECOS). Methods TECOS randomized 14,671 participants with type 2 diabetes and atherosclerotic cardiovascular disease (ASCVD) to sitagliptin or placebo, in addition to usual care. For those who had a within-trial MI, we analyzed case fatality, and for those with a nonfatal MI, we examined a composite cardiovascular (CV) outcome (CV death or hospitalization for heart failure [hHF]) by treatment group, using Cox proportional hazards models left-censored at the time of the first within-trial MI, without and with adjustment for potential confounders, in intention-to-treat analyses. Results During TECOS, 616 participants had >= 1 MI (sitagliptin group 300, placebo group 316, HR 0.95, 95% CI 0.81-1.11, P = 0.49), of which 25 were fatal [11 and 14, respectively]). Of the 591 patients with a nonfatal MI, 87 (15%) died subsequently, with 66 (11%) being CV deaths, and 57 (10%) experiencing hHF. The composite outcome occurred in 58 (20.1%; 13.9 per 100 person-years) sitagliptin group participants and 50 (16.6%; 11.7 per 100 person-years) placebo group participants (HR 1.21, 95% CI 0.83-1.77, P = 0.32, adjusted HR 1.23, 95% CI 0.83-1.82, P = 0.31). On-treatment sensitivity analyses also showed no significant between-group differences in post-MI outcomes. Conclusions In patients with type 2 diabetes and ASCVD experiencing an MI, sitagliptin did not reduce subsequent risk of CV death or hHF, contrary to expectations derived from preclinical animal models. Trial registration no. NCT00790205