Pramlintide
Fuentes regulatorias consultadas
Indicaciones aprobadas
- Tratamiento complementario en diabetes tipo 1 o tipo 2 para pacientes que utilizan insulina prandial y no alcanzan el control glucémico deseado pese a una insulinoterapia óptima.
Contraindicaciones
Absolutas
- Reacción de hipersensibilidad grave a pramlintida o a alguno de sus componentes.
- Desconocimiento o ausencia de percepción de la hipoglucemia.
- Gastroparesia confirmada.
Advertencias clínicas
- Advertencia destacada (boxed warning) · Advertencia en recuadro: aumenta el riesgo de hipoglucemia grave, especialmente con insulina prandial; no iniciar sin plan de vigilancia y ajuste. — DailyMed SYMLIN setid 4aea30ff-eb0d-45c1-b114-3127966328ff
Interacciones medicamentosas
- ModeradaMedicamentos orales
Mecanismo: Pramlintida retrasa el vaciamiento gástrico.
Recomendación: Administrar medicamentos orales al menos 1 hora antes o 2 horas después.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ffDailyMed setid 4aea30ff-eb0d-45c1-b114-3127966328ff
- ModeradaInsulina
Mecanismo: La mezcla altera la farmacocinética de ambos productos.
Recomendación: Nunca mezclar pramlintida e insulina en la misma jeringa.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ffDailyMed setid 4aea30ff-eb0d-45c1-b114-3127966328ff
- SeveraFármacos que alteran la motilidad gastrointestinal, incluidos anticolinérgicos como atropina
Mecanismo: Pramlintida retrasa el vaciamiento gástrico; estos medicamentos pueden producir efectos aditivos sobre la motilidad.
Recomendación: No considerar pramlintida en pacientes que requieren estos medicamentos.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff
- SeveraInhibidores de la alfa-glucosidasaA10BF
Mecanismo: Retrasan la absorción intestinal de nutrientes y no se estudiaron junto con pramlintida.
Recomendación: No considerar pramlintida en pacientes que requieren inhibidores de la alfa-glucosidasa.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff
- SeveraMedicamentos que aumentan la susceptibilidad a la hipoglucemia
Mecanismo: Antidiabéticos, IECA, disopiramida, fibratos, fluoxetina, IMAO, pentoxifilina, salicilatos, análogos de somatostatina y sulfamidas antibacterianas pueden aumentar la susceptibilidad a la hipoglucemia.
Recomendación: Coadministrar con cautela y reforzar la monitorización de la glucemia y los ajustes de insulina.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4aea30ff-eb0d-45c1-b114-3127966328ff
Eventos adversos
Comunes (≥1%)
Náuseas · Vómitos · Disminución del apetito · Cefalea · Fatiga · Mareo
Raros pero graves
Hipoglucemia grave · Pancreatitis · Reacción de hipersensibilidad grave
Embarazo y lactancia
Usar en embarazo solo si el beneficio justifica el riesgo; se desconoce si pasa a la leche humana.
Bibliografía reciente (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.