Nowadays, GLP-1 receptor agonists are widely used as effective and safe antidiabetic medications. In addition to glucose-dependent insulin secretion, their effects reach beyond glucose control. Previously, it has been shown that acute administration of GLP-1 receptor agonists increases circulating glucocorticoid and mineralocorticoid levels in both humans and rodents. So far, no studies have reported the effects of chronic administration of GLP-1 receptor agonists on the hypothalamic-pituitary-adrenal axis in humans. The aim of the current study was to examine the effects of acute and chronic treatment with the GLP-1 receptor agonist liraglutide on adrenal function in humans. Ten healthy volunteers were recruited into a single group open-label clinical trial. Each participant was tested for baseline levels, and after acute and chronic treatment with 0.6 mg liraglutide daily. A graded glucose infusion test was performed 3 times. We found that aldosterone tended to be suppressed (albeit not statistically different) after acute administration of liraglutide, and increased after chronic dosing; the difference was statistically significant when compared between acute and chronic dosing. Changes in aldosterone levels followed the changes in renin concentrations and the aldosterone-to-renin ratio remained stable. No statistically significant differences were observed in ACTH or cortisol levels. In conclusion, we have shown that a low dose of GLP-1 receptor agonist may interfere with renin and aldosterone release. Further studies in a larger patient sample and with higher doses of GLP-1 receptor agonists are warranted to corroborate this finding. The study protocol was registered at clinical.trials.gov (NCT02089256) and EU Clinical Trial Register (2014-000238-43).

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are antidiabetic drugs with effects beyond antihyperglycemic action. The aim of the study was to examine whether a single dose of exenatide could be used as a stimulation test for the pituitary-adrenal axis. We carried out a single-group, open-label pilot clinical trial in an ambulatory setting. Ten healthy volunteers of both sexes with body weight>65 kg and age between 18–50 years were recruited. After fasting for 12 hours the subjects received 10 μg of exenatide solution subcutaneously. Blood samples were taken before the administration of exenatide and up to 150 minutes thereafter. The primary outcome was the maximal level of cortisol after the administration of exenatide. Single administration of exenatide 10 μg resulted in a modest increase in ACTH and cortisol levels, as compared to untreated values, and a decrease in blood glucose levels. Remarkably, a robust suppression of both renin and aldosterone levels occurred. We showed that acute administration of exenatide in a full therapeutic dose modestly stimulates the hypothalamic-pituitary-adrenal axis but inhibits the renin-aldosterone system. Further research is warranted to confirm this finding in the placebo-controlled study.

Background Safety of sulfonylurea drugs in the treatment of Type 2 Diabetes is still under debate. The aim of this study was to compare the all-cause mortality and cardiovascular adverse events of sulfonylureas and drugs with a low risk for hypoglycaemia in adults with type 2 diabetes. Methods Systematic review and meta-analysis of randomised controlled trials. Data sources: MEDLINE (PubMed, OVID), Embase, Cochrane Central Register of Controlled Trials, CINAHL, WOS and Lilacs. Study selection Randomised controlled head-to-head trials that compared sulfonylureas with active control with low hypoglycaemic potential in adults (≥ 18 years old) with type 2 diabetes published up to August 2015. The drug classes involved in the analysis were metformin, dipeptidyl peptidase-4 (DPP-4) inhibitors, sodium-glucose co-transporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists. Outcomes The primary endpoint was all-cause mortality. The secondary endpoints were MACE, cardiovascular events and severe hypoglycaemia. Synthesis of results: Two reviewers checked study eligibility, independently extracted data and assessed quality with disagreements resolved through discussion. We assessed the risk of bias of the included studies using the Cochrane risk of bias tool for randomized trials v2. Pooled odds ratios (ORs) were estimated by using fixed effects model. The study is registered on PROSPERO (26/05/2016 CRD42016038780). Results Our final analysis comprised 31 studies (26,204 patients, 11,711 patients given sulfonylureas and 14,493 given comparator drugs). In comparison to drugs with low hypoglycaemic potential, sulfonylureas had higher odds for all-cause mortality (OR 1.32, 95% CI 1.00-1.75), MACE (OR 1.32, 95% CI 1.07–1.61), myocardial infarction (fatal and non-fatal) (OR 1.67, 95% CI 1.17–2.38) and hypoglycaemia (OR 5.24, 95% CI 4.20–6.55). Subsequent sensitivity analysis revealed differences in the effect of sulfonylureas, with an increased risk of all-cause mortality with glipizide but not the other molecules. Conclusion Our meta-analysis raises concern about the safety of SUs compared to alternative drugs involved in current analysis. Important differences may exist within the drug class, and glimepiride seems to have best safety profile.

No abstract

No abstract