Exenatide
Sources réglementaires consultées
Indications approuvées
- Traitement de l'adulte atteint de diabète de type 2 en association avec d'autres médicaments hypoglycémiants lorsque ceux-ci, avec le régime alimentaire et l'exercice, n'assurent pas un contrôle glycémique suffisant.
Contre-indications
Absolues
- Hypersensibilité à l'exénatide
- Antécédent de thrombopénie immunitaire induite par l'exénatide
Mises en garde cliniques
- Mise en garde majeure · Des pancréatites, une détérioration rénale, une hypoglycémie avec l'insuline ou les sécrétagogues, une thrombopénie et des réactions d'hypersensibilité ont été signalées. Éviter en cas de gastroparésie sévère. — CIMA BYETTA 06362001 / DailyMed e6cb5c8f-e97f-4a6a-95a4-939fd2393949
- Mise en garde majeure · Des événements aigus de la vésicule biliaire, notamment une cholélithiase et une cholécystite, ont été rapportés. En cas de suspicion, réaliser des examens de la vésicule et un suivi clinique approprié. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e6cb5c8f-e97f-4a6a-95a4-939fd2393949
- Mise en garde majeure · De rares cas d'inhalation pulmonaire ont été rapportés lors d'une intervention ou d'un acte sous anesthésie générale ou sédation profonde, malgré un jeûne préopératoire déclaré. Informer l'équipe soignante avant tout acte programmé ; les données de la notice ne permettent pas d'établir si une modification du jeûne ou un arrêt temporaire de l'exénatide réduit le risque. — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e6cb5c8f-e97f-4a6a-95a4-939fd2393949
Interactions médicamenteuses
- ModéréeMédicaments oraux à marge thérapeutique étroite ou nécessitant une absorption rapide
Mécanisme: L'exénatide ralentit la vidange gastrique et peut réduire la vitesse et l'ampleur de l'absorption orale.
Recommandation: Surveiller étroitement et standardiser la prise par rapport à l'injection. Administrer les médicaments dépendant d'une concentration seuil, comme les antibiotiques, au moins 1 heure avant ; administrer les formes gastro-résistantes au moins 1 heure avant ou plus de 4 heures après.
https://cima.aemps.es/cima/dochtml/ft/06362001/FT_06362001.htmlCIMA registro 06362001
- ModéréeWarfarine et dérivés coumariniquesB01AA03
Mécanisme: Des augmentations de l'INR ont été signalées pendant l'administration concomitante.
Recommandation: Surveiller fréquemment l'INR lors de l'instauration de l'exénatide et pendant l'augmentation de la dose.
https://cima.aemps.es/cima/dochtml/ft/06362001/FT_06362001.htmlhttps://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=e6cb5c8f-e97f-4a6a-95a4-939fd2393949
Effets indésirables
Communs (≥1%)
Nausées · Vomissements · Diarrhée · Diminution de l'appétit · Céphalées · Étourdissements · Hypoglycémie avec une sulfonylurée
Rares mais graves
Pancréatite aiguë · Insuffisance rénale aiguë · Thrombopénie immunitaire · Réaction anaphylactique · Cholélithiase ou cholécystite aiguë · Inhalation pulmonaire pendant une anesthésie générale ou une sédation profonde
Grossesse et allaitement
Arrêter l'exénatide si une grossesse est prévue ou survient. Ne pas utiliser pendant la grossesse ; l'insuline est recommandée. Ne pas utiliser pendant l'allaitement.
Bibliographie récente (PubMed)
Psychotropic drug-related weight gain (PDWG) is a common occurrence and is highly associated with non-initiation, discontinuation, and dissatisfaction with psychiatric drugs. Moreover, PDWG intersects with the elevated risk for obesity and associated morbidity that has been amply reported in the psychiatric population. Evidence indicates that differential liability for PDWG exists for antipsychotics, antidepressants, and anticonvulsants. During the past two decades, agents within these classes have become available with significantly lower or no liability for PDWG and as such should be prioritized. Although lithium is associated with weight gain, the overall extent of weight gain is significantly lower than previously estimated. The benefit of lifestyle and behavioral modification for obesity and/or PDWG in psychiatric populations is established, with effectiveness similar to that in the general population. Metformin is the most studied pharmacological treatment in the prevention and treatment of PDWG, and promising data are emerging for glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide, exenatide, semaglutide). Most pharmacologic antidotes for PDWG are supported with low-confidence data (e.g., topiramate, histamine-2 receptor antagonists). Future vistas for pharmacologic treatment for PDWG include large, adequately controlled studies with GLP-1 receptor agonists and possibly GLP-1/glucose-dependent insulinotropic polypeptide co-agonists (e.g., tirzepatide) as well as specific dietary modifications.
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated significant cardiovascular (CV) benefits, particularly in patients with diabetes mellitus, but the safety and efficacy of different GLP-1 RAs across diverse populations remain insufficiently defined. Previous meta-analyses of GLP-1 RAs have been limited by restricted populations, omission of recent trials, or incomplete safety synthesis; this study integrates the latest evidence across 21 randomized controlled trials and diverse populations using advanced meta-analytic methods. Randomized controlled trials comparing GLP-1 RAs vs controls or placebo were included. Analyses were conducted in prespecified subgroups based on the GLP-1 RA used. Prespecified subgroups according to diabetes mellitus, kidney function, obesity, or heart failure were also performed. Main outcomes comprised mortality (all-cause and CV), trial-defined major adverse cardiovascular events (MACE) and serious adverse events. GRADE (Grading of Recommendations Assessment, Development and Evaluation) and trial sequential analyses were performed to evaluate certainty and conclusiveness of findings, respectively. A total of 21 trials encompassing 99,599 patients were included. Eight different GLP-1 RAs were used (lixisenatide, liraglutide, exenatide, semaglutide, efpeglenatide, dulaglutide, albiglutide, and tirzepatide), each administered at therapeutic doses and compared vs placebo or controls. Mean follow-up duration was 2.4 years. We found conclusive, high-certainty evidence that GLP-1 RAs reduced all-cause death (incidence rate ratio [IRR]: 0.88; 95% CI: 0.84-0.92; needed to treat [NNT] = 121), CV death (IRR: 0.87; 95% CI: 0.81-0.92; NNT = 170), and MACE (IRR: 0.87; 95% CI: 0.83-0.91; NNT = 66), compared with controls. GLP-1 RAs reduced serious adverse events (-9%), myocardial infarction (-15%), acute kidney failure (-9%), heart failure (-15%), and infections (-10%), but increased gastrointestinal (+63%) and gallbladder (+26%) d
In the last few years, a great interest has emerged in investigating the pleiotropic effects of Glucagon Like Peptide-1 Receptor Agonists (GLP-1RAs). While GLP-1RAs ability to lower plasma glucose and to induce weight loss has allowed them to be approved for the treatment of diabetes and obesity, consistent evidences from in vitro studies and preclinical models suggested that GLP-1RAs have anti-inflammatory properties and that may modulate the immune-system. Notably, such anti-inflammatory effects target different pathways in different tissues, underling the broad spectrum of GLP-1RAs actions. This review examines some of the currently proposed molecular mechanisms of GLP-1RAs actions and explores their potential benefits in reducing inflammatory responses, which may well suggest a future therapeutic use of GLP-1RAs in new indications.
Obesity is a chronic disease with high prevalence and associated comorbidities, making it a growing global concern. These comorbidities include type 2 diabetes, hypertension, ventilatory dysfunction, arthrosis, venous and lymphatic circulation diseases, depression, and others, which have a negative impact on health and increase morbidity and mortality. GLP-1 agonists, used to treat type 2 diabetes, have been shown to be effective in promoting weight loss in preclinical and clinical studies. This review summarizes numerous studies conducted on the main drugs in the GLP-1 agonists class, outlining the maximum achievable weight loss. Our aim is to emphasize the active role and main outcomes of GLP-1 agonists in promoting weight loss, as well as in improving hyperglycemia, insulin sensitivity, blood pressure, cardio-metabolic, and renal protection. We highlight the pleiotropic effects of these medications, along with their indications, contraindications, and precautions for both diabetic and non-diabetic patients, based on long-term follow-up studies.
Obesity is frequently a comorbidity of type 2 diabetes. Even modest weight loss can significantly improve glucose homeostasis and lessen cardiometabolic risk factors in patients with type 2 diabetes, but lifestyle-based weight loss strategies are not long-term effective. There is an increasing need to consider pharmacological approaches to assist weight loss in the so called diabesity syndrome. Aim of this review is to analyze the weight-loss effect of non-insulin glucose lowering drugs in patients with type 2 diabetes. A systematic analysis of the literature on the effect of non-insulin glucose lowering drugs on weight loss in patients with type 2 diabetes was performed. For each class of drugs, the following parameters were analyzed: kilograms lost on average, effect on body mass index and body composition. Our results suggested that anti-diabetic drugs can be stratified into 3 groups based on their efficacy in weight loss: metformin, acarbose, empagliflozin and exenatide resulted in a in a mild weight loss (less than 3.2% of initial weight); canagliflozin, ertugliflozin, dapagliflozin and dulaglutide induces a moderate weight loss (between 3.2% and 5%); liraglutide, semaglutide and tirzepatide resulted in a strong weight loss (greater than 5%). This study shows that new anti-diabetic drugs, particularly GLP1-RA and Tirzepatide, are the most effective in inducing weight loss in patients with type 2 diabetes. Interestingly, exenatide appears to be the only GLP1-RA that induces a mild weight loss.