Long-term effects of GLP-1 receptor agonists in type 2 diabetic patients: A retrospective real-life study in 131 patients.

AIM: We evaluate retrospectively long-term effects of GLP-1 receptor agonists in type 2 diabetic patients treated between 2008 and 2016. METHODS: 131 patients treated by GLP-1 receptor agonists (GLP-1RAs) were included. The objective was to evaluate the evolution of glycated hemoglobin (HbA1c) during a period up to 4 years. The secondary objectives consisted of analysing the long-term effects of treatment on body mass index (BMI), blood pressure and lipids; reporting the proportion of patients who reached HbA1c objectives; estimating the time before treatment failure and determining predictive factors of failure. We also compared twice-daily exenatide to once-daily liraglutide on the major parameters. RESULTS: HbA1c improved significantly, mostly during the first year of treatment (-1.2%), and this effect was maintained after 4 years (-1.4% vs. baseline). At 1 year, 26% and 47% of subjects achieved HbA1c levels <7.0% and 7.5%, respectively. Treatment failure was observed in 51% of patients after a mean duration of GLP-1RA treatment of 50 months. Half of patients had failed after 42 months. Baseline HbA1c greater than 9.0% and male gender were predictive factors of treatment failure. BMI also decreased: -0.9 kg/m2 the first year, -1.9 kg/m2 after 4 years. No significant difference was found between patients treated with exenatide and liragutide over time. CONCLUSIONS: The beneficial effects of GLP-1RAs on HbA1c reached a plateau after the first year of treatment and are maintained at 4 years only in one third of patients. Failure occurred predominantly in men with a baseline HbA1c greater than 9%.

Acute and chronic alcohol use correlated with methods of suicide in a Swiss national sample.

OBJECTIVES: Chronic and acute alcohol use are highly associated risk factors for suicides worldwide. Therefore, we examined suicide cases with and without alcohol use disorder (AUD) using data from the SNSF project "Suicide in Switzerland: A detailed national survey". Our investigations focus on correlations between acute and chronic alcohol use with reference to suicide and potential interactions with the methods of suicide. METHODS: We used data from the SNSF project in which all cases of registered completed suicide in Switzerland reported to any of the seven Swiss institutes of legal and forensic medicine between 2000 and 2010 were collected. We extracted cases that were tested for blood alcohol to use in our analysis. We compared clinical characteristics, blood alcohol concentrations, and methods of suicide in cases with and without AUD. RESULTS: Out of 6497 cases, 2946 subjects were tested for acute alcohol use and included in our analysis. Of the latter, 366 (12.4%) persons had a medical history of AUD. Subjects with AUD significantly had higher blood alcohol concentrations and were more often in medical treatment before suicide. Drug intoxication as method of suicide was more frequent in cases with AUD compared to NAUD. CONCLUSION: Overall, we found a high incidence of acute alcohol use at the time of death in chronic alcohol misusers (AUD). The five methods of suicide most commonly used in Switzerland differed considerably between individuals with and without AUD. Blood alcohol concentrations varied across different methods of suicide independently from the medical history in both groups.

Regulation of galanin secretion from pituitary cells in vitro by estradiol and GHRH.

The effects of estradiol and growth hormone-releasing hormone (GHRH) on galanin release from anterior pituitary cells were examined in vitro. 17-beta-Estradiol (0.001-10 nM) increased galanin secretion from anterior pituitary cells in a concentration-dependent manner. Estradiol (10 nM) increased galanin release 300 and 600% from pituitary cells of ovariectomized and male rats, respectively. Immunocytochemical studies demonstrated that estradiol (10 nM) increased the number of galanin-containing cells twofold after 4 days in culture. Growth hormone-releasing hormone (1 and 10 nM) increased and SRIF (1 and 10 nM) decreased galanin release from pituitary cells of ovariectomized and male rats. We conclude that estradiol increases galanin release by a direct effect on pituitary cells, in part by increasing the number of pituitary cells synthesizing galanin. In addition, GHRH stimulates galanin release when estradiol levels are low.