Chaperone Therapy in Fabry Disease.

Fabry disease is an X-linked lysosomal multisystem storage disorder induced by a mutation in the alpha-galactosidase A (GLA) gene. Reduced activity or deficiency of alpha-galactosidase A (AGAL) leads to escalating storage of intracellular globotriaosylceramide (GL-3) in numerous organs, including the kidneys, heart and nerve system. The established treatment for 20 years is intravenous enzyme replacement therapy. Lately, oral chaperone therapy was introduced and is a therapeutic alternative in patients with amenable mutations. Early starting of therapy is essential for long-term improvement. This review describes chaperone therapy in Fabry disease.

Comparative evaluation of incretin-based antidiabetic medications and alternative therapies to be added to metformin in the case of monotherapy failure.

UNLABELLED: Aims/Introduction: To compare clinical consequences of using inretin-based medications versus conventional antidiabetic agents as add-on to metformin in case of monotherapy failure in patients with type 2 diabetes. MATERIALS AND METHODS: The medical literature including recent abstracts from international diabetes conferences was searched for reports from clinical trials with incretin mimetics (GLP-1 receptor agonists), inhibitors of dipeptidyl peptidase-4 (DPP-4, incretin enhancers) and conventional antidiabtic drugs coadministered with metformin after monotherapy failure. A scoring system is suggested to compare the clinical utility of using incretin-based versus conventional antidiabetic agents in this situation. RESULTS: Incretin mimetics and DPP-4 inhibitors on top of metformin treatment help achieve glycaemic control comparable to other efficient antidiabetic drugs, both if separate or head-to-head trials were considered. Incretin-based antidiabetic drugs did not cause hypoglycaemia (different from sulfonylureas, meglitinides and insulin) and weight gain (different from sulfonylureas, meglitinides, thiazolidinediones, and insulin). DPP-4 inhibitors were weight neutral, incretin mimetics lead to weight loss. The clinical profile of incretin-based medications received the highest scores, followed by α-glucosidase inhibitors, with far lower scores assigned to insulin, glitazones, and sulfonyureas (in this order). CONCLUSIONS: Based on the results from clinical trials, incretin-based medications have been shown to be efficacious antidiabetic drugs with a favourable adverse event and tolerability profile. This leads to high scores using a novel system paying attention to multiple facets contributing to the selection of antidiabetic drugs for general recommendation and individual treatment choices.