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Introduction: Dulaglutide (Trulicity â) is a long-acting glucagon-like peptide 1 (GLP-1) receptor agonist indicated in adults with type 2 diabetes mellitus. Data about the safety profile of dulaglutide are lacking due to the lack of experience with this recently marketed drug. Material and methods: We report the first case of a beneficial effect of dulaglu-tide. Results: A 48-year-old woman with hypertension, cardiac insufficiency and depression was treated with amlodipine, valsartan, spironolactone, nebivolol, atorvastatine, esomeprazole, escitalopram, oxazepam and tramadol. She had lower limb edema since a lot of months. For diabetes mellitus, dulaglutide (1.5 mg once a week) was started and the lower limb edema began to improve. Three months later, the lower limb edema has disappeared without any new treatment. The dulaglutide had to be interrupted for 2 months and edema recurred. The use of hydrochlorothiazide (25 mg/day) had no effect but the lower limb edema disappeared again after dulaglutide was resumed while all the other drugs were maintained. Discussion/Conclusion: The temporal relationship between dulaglutide treatment and regression of the edema is in favour of the role of dulaglutide and the role of the other drugs, continuously maintained, is ruled out. No regression of edema had been previously reported with dulaglutide. However, animal studies suggest that GLP-1 or its agonists have diuretic and natriuretic effects, which are mediated by an increase in renal plasma flow and glomerular filtration rate, as well as a decrease in the proximal reabsorption of sodium with an increase in fractional sodium excretion [1,2]. Moreover, GLP-1 reduced Na + /H + exchanger isoform 3 (NHE3)-mediated bicarbonate reabsorption in the renal proximal tubule, resulting in a decrease of sodium, bicarbonate and water reabsorption. A study in humans concluded that liraglutide, another GLP-1 agonist, decreases the proximal tubular sodium reabsorption, but has no effect on glomerular filtration rate or renal blood flow [3]. Thus, the GLP-1 agonists and especially dulaglutide could probably have a potential interest in disorders of sodium retention. References [1] Crajoinas RO et al. Mechanisms mediating the diuretic and natriuretic actions of the incretin hormone glucagon-like peptide-1. Am. [3] Skov J et al. Short-term effects of liraglutide on kidney function and vasoac-tive hormones in type 2 diabetes: a randomized clinical trial. Diabetes Obes. Metab. (2016) 18: 581-589. PS1-002 A comparative study of QT prolongation with Serotonin Reuptake Inhibitors (SRIs) A Senard-Ojedo, L Chebane, M Araujo, V Rousseau, F Montastruc, JL Montastruc Laboratoire de Pharmacologie M edicale et Clinique, Centre Midi-Pyr en ees de PharmacoVigilance, de Pharmaco epid emiologie et d'Informations sur le M edicament, Pharmacop^ ole Midi-Pyr en ees, INSERM UMR 1027, CHU et Facult e de M edecine-Toulouse (France) Introduction: QT interval prolongations were described with citalopram or esci-talopram. However, the effects of the other SRIs remai...

SUMMARY1. The aim of the present study was to clarify the mechanisms mediating the effect of a glucagon-like peptide-1 (GLP-1) mimetic on solute-free water excretion in rats.2. The GLP-1 mimetic exenatide (0.05-5.0 nmol/kg, i.m.), alone and in combination with either a vasopressin V 2 receptor antagonist (15 nmol/kg, i.p.) or vasopressin (0.01 nmol/kg, i.m.), was injected into control and water-loaded (water 10-50 mL/kg, p.o., or 50 mL/kg of 0.6% NaCl, i.p.) rats to evaluate the role of collecting duct water permeability in the hydrouretic effect. Urinary prostaglandin (PG) E 2 excretion and the effects of diclofenac (5 mg/kg, i.m.) and GLP-1 receptor antagonist (0.15 lmol/kg, i.p.) on exenatide action were assessed.3. The hydrouretic effect of exenatide was equivalent following oral or intraperitoneal water loading, and was proportional to the volume of water administered. Injection of exenatide, under conditions of a maximal decrease in collecting duct water permeability (V 2 receptor antagonist administration in waterloaded rats), additionally stimulated solute-free water formation. The GLP-1 receptor antagonist weakened the hydrouretic action of exenatide. Urinary PGE 2 excretion increased following water loading (47 AE 6 vs 24 AE 4 ng/kg over a 30 min period) and was enhanced as a result of additional exenatide injection (69 AE 10 ng/kg). Diclofenac and vasopressin delayed the hydrouretic effect of exenatide.4. The effect of exenatide on solute-free water clearance in water-loaded rats is presumably mediated by stimulation of PGE 2 secretion and reinforcement of tubular fluid influx from the proximal tubule to the distal segment of the nephron and collecting duct.

Blood concentration of glucagon-like peptide-1 (GLP-1) increased 5 min after per os administration of water, sodium chloride solution, or glucose solution. Changes in blood osmolality or blood glucose level did not stimulate GLP-1 release. A method of short-term increase in the gastric capacity in rats using an inflating balloon attached to the Foley catheter was developed in order to test the hypothesis that excitation of the upper gastrointestinal tract receptors is a primary signal for the GLP-1 secretion during oral intake of the substances. Mechanical gastric distension in rats caused elevation of the blood GLP-1 concentration which was comparable to the effects of oral administration of water, sodium chloride, and glucose solutions.

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