Pramlintide
Sources réglementaires consultées
Indications approuvées
- Traitement complémentaire du diabète de type 1 ou de type 2 chez les patients utilisant une insuline prandiale qui n'ont pas atteint le contrôle glycémique souhaité malgré une insulinothérapie optimale.
Contre-indications
Absolues
- Réaction d'hypersensibilité grave au pramlintide ou à l'un de ses composants.
- Méconnaissance ou absence de perception de l'hypoglycémie.
- Gastroparésie confirmée.
Mises en garde cliniques
- Mise en garde encadrée · Avertissement encadré : augmente le risque d'hypoglycémie sévère, surtout avec l'insuline prandiale ; ne pas instaurer sans plan de surveillance et d'ajustement. — DailyMed SYMLIN setid 4aea30ff-eb0d-45c1-b114-3127966328ff
Interactions médicamenteuses
- ModéréeMédicaments oraux
Mécanisme: Le pramlintide ralentit la vidange gastrique.
Recommandation: Administrer les médicaments oraux au moins 1 heure avant ou 2 heures après.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ffDailyMed setid 4aea30ff-eb0d-45c1-b114-3127966328ff
- ModéréeInsuline
Mécanisme: Le mélange modifie la pharmacocinétique des deux produits.
Recommandation: Ne jamais mélanger le pramlintide et l'insuline dans la même seringue.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ffDailyMed setid 4aea30ff-eb0d-45c1-b114-3127966328ff
- SévèreMédicaments modifiant la motilité gastro-intestinale, notamment les anticholinergiques comme l'atropine
Mécanisme: Le pramlintide ralentit la vidange gastrique ; ces médicaments peuvent avoir des effets additifs sur la motilité.
Recommandation: Ne pas envisager le pramlintide chez les patients nécessitant ces médicaments.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff
- SévèreInhibiteurs de l'alpha-glucosidaseA10BF
Mécanisme: Ils ralentissent l'absorption intestinale des nutriments et n'ont pas été étudiés avec le pramlintide.
Recommandation: Ne pas envisager le pramlintide chez les patients nécessitant des inhibiteurs de l'alpha-glucosidase.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff
- SévèreMédicaments augmentant la sensibilité à l'hypoglycémie
Mécanisme: Les antidiabétiques, les IEC, le disopyramide, les fibrates, la fluoxétine, les IMAO, la pentoxifylline, les salicylés, les analogues de la somatostatine et les sulfamides antibactériens peuvent augmenter la sensibilité à l'hypoglycémie.
Recommandation: Administrer avec prudence et renforcer la surveillance de la glycémie ainsi que l'ajustement de l'insuline.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff
Effets indésirables
Communs (≥1%)
Nausées · Vomissements · Diminution de l'appétit · Céphalées · Fatigue · Étourdissements
Rares mais graves
Hypoglycémie sévère · Pancréatite · Réaction d'hypersensibilité grave
Grossesse et allaitement
Utiliser pendant la grossesse uniquement si le bénéfice justifie le risque ; on ignore si le médicament passe dans le lait humain.
Bibliographie récente (PubMed)
People with type 1 diabetes (T1D) are usually considered to exclusively exhibit β-cell failure, but they frequently also feature insulin resistance. This review discusses the mechanisms, clinical features, and therapeutic relevance of insulin resistance by focusing mainly on human studies using gold-standard techniques (euglycemic-hyperinsulinemic clamp). In T1D, tissue-specific insulin resistance can develop early and sustain throughout disease progression. The underlying pathophysiology is complex, involving both metabolic- and autoimmune-related factors operating synergistically. Insulin treatment may play an important pathogenic role in predisposing individuals with T1D to insulin resistance. However, the established lifestyle-related risk factors and peripheral insulin administration inducing glucolipotoxicity, hyperinsulinemia, hyperglucagonemia, inflammation, mitochondrial abnormalities, and oxidative stress cannot always fully explain insulin resistance in T1D, suggesting a phenotype distinct from type 2 diabetes. The mutual interaction between insulin resistance and impaired endothelial function further contributes to diabetes-related complications. Insulin resistance should therefore be considered a treatment target in T1D. Aside from lifestyle modifications, continuous subcutaneous insulin infusion can ameliorate insulin resistance and hyperinsulinemia, thereby improving glucose toxicity compared with multiple injection insulin treatment. Among other concepts, metformin, pioglitazone, incretin-based drugs such as GLP-1 receptor agonists, sodium-glucose cotransporter inhibitors, and pramlintide can improve insulin resistance, either directly or indirectly. However, considering the current issues of high cost, side effects, limited efficacy, and their off-label status, these agents in people with T1D are not widely used in routine clinical care at present.
Diabetes mellitus is a devastating chronic metabolic disease. Since the majority of type 2 diabetes mellitus patients are overweight or obese, a novel term-diabesity-has emerged. The gut-brain axis plays a critical function in maintaining glucose and energy homeostasis and involves a variety of peptides. Amylin is a neuroendocrine anorexigenic polypeptide hormone, which is co-secreted with insulin from β-cells of the pancreas in response to food consumption. Aside from its effect on glucose homeostasis, amylin inhibits homeostatic and hedonic feeding, induces satiety, and decreases body weight. In this narrative review, we summarized the current evidence and ongoing studies on the mechanism of action, clinical pharmacology, and applications of amylin and its analogs, pramlintide and cagrilintide, in the field of diabetology, endocrinology, and metabolism disorders, such as obesity.
Obesity is a pandemic, linked with increased morbidity including diabetes mellitus (DM) and certain cancer types. Amylin is a major regulatory hormone for satiation and food intake perception in humans. Amylin analogs (pramlintide and cagrilintide) are emerging as promising anti-obesity agents in non-DM subjects. Pramlintide, the first amylin analog, initially used for the treatment of both type 1 and type 2 DM, has demonstrated weight-lowering action. Clinical trials confirmed a weight loss exceeding 3% in the study period without major untoward effects, which was maintained beyond the follow-up period. Recently, cagrilintide, a long-lasting synthetic amylin analog has been introduced. Cagrilintide has achieved adequate weight loss, reaching even more than 10% of the total weight in early clinical trials. However, adverse gastrointestinal effects, particularly nausea, were more frequent compared with pramlintide. Clinical trials have also confirmed the effectiveness of cagrilintide in comparison with glucagon-like peptide 1 receptor agonists. Amylin analogs will certainly enrich the growing therapeutic armamentarium aimed at tackling obesity. The most exciting future research venue could be the development of their combinations with other weight-lowering drugs, especially dual and triple incretin-based co-agonists, thus potentially providing massive weight-loss effects.
Amylin is a glucoregulatory peptide hormone discovered in 1986. Almost 20 years later, pramlintide, a human amylin analogue, emerged as the first amylin-based drug, approved as an adjunct treatment to insulin for type 1 diabetes (T1D) and type 2 diabetes (T2D). Despite its effects on multiple organ systems, the therapeutic potential of amylin has remained relatively underexplored until recently, when growing interest in amylin has prompted advancement of several amylin-based therapies towards clinical use. This Review contextualizes the evolving therapeutic potential of amylin, focusing on recent preclinical and clinical data, amylin receptor pharmacology and its broader biological effects. We discuss the potential and challenges of developing amylin-based treatments for cardiometabolic disease, including milestones in drug development of amylin, and its combination with additional molecules as part of the future landscape of therapies for patients with diabetes or obesity.
The identification of amylin as a glucoregulatory peptide hormone with roles in meal-ending satiation sparked a surge of experimental development, which culminated in the amylin mimetic drug pramlintide. Pramlintide was approved by the FDA in 2005 for the treatment of type 1 diabetes mellitus and insulin-requiring type 2 diabetes, and was also explored as a novel anti-obesity treatment. Despite this exciting potential, efforts to develop an amylin-based anti-obesity therapeutic stalled owing to challenges around dosage frequency, safety and formulation. Generally, anti-obesity therapies have displayed modest efficacy and mixed safety profiles, leaving a clear unmet clinical need that requires addressing. Advances in peptide chemistry have reinvigorated the amylin field by enabling the manufacture of effective new amylin-based molecules, resulting in therapeutics that are now on the cusp of approval. At present, there are growing concerns around GLP1 receptor agonist-based therapeutics, in particular their association with loss of lean body mass. Additionally, treatment of patients with overweight or obesity without associated comorbidities is increasingly common. The widespread pharmacotherapy of otherwise healthy populations with overweight or obesity with the goal of improving future health requires further regulatory and ethical consideration. This Review describes how amylin controls energy homeostasis and provides a current overview of amylin-based therapeutic development.