[The thiazolidinones--a new therapeutic agent for type 2 diabetes].
Both, impaired beta-cell function and insulin resistance, predominantly of the skeletal muscle, are considered to be the key factors in the pathogenesis of type-2 diabetes (non-insulin-dependent diabetes; NIDDM). In the early stage of the disease, impaired insulin-mediated glucose disposal is accompanied by increased insulin secretion and hyperinsulinaemia. The thiazolidinediones (e.g. troglitazone), by improving insulin sensitivity of target tissues, appear to be a novel pathophysiologically interesting approach for the treatment of patients with NIDDM or impaired glucose tolerance. Troglitazone mainly elicits the following actions: Enhancement of insulin-mediated glucose disposal in patients with insulin resistance, impaired glucose tolerance and NIDDM, reduction of hyperglycaemia (blood glucose; HbA1c) and concomitant hyperinsulinaemia, improvement of dyslipidaemia in NIDDM. These actions are attained with monotherapy (200-600 mg once daily; plasma concentrations 0.3-3.0 micrograms/ml) or, with increased effects, when troglitazone is added to previously insufficient treatment with sulfonylureas or insulin. Potentially therapeutic actions with clinical relevance include (a) improvement of insulin resistance-associated hyperglycaemia-independent states of dyslipidaemia, (b) inhibition of LDL-oxidation and (c) amelioration of function and/or protection of beta-cells, an effect indicating to a beneficial modulation of the second pathogenetic relevant factor of NIDDM. Troglitazone appears to be well tolerated by the majority of patients. Post-marketing reports of partly severe liver injury including deaths from liver failure among Japanese and U.S. patients taking troglitazone require a critical evaluation of the benefit to risk ratio of the drug and a careful monitoring of the patients.
Bethge
H
H
Medizinische Klinik, Klinikum Darmstadt.
Häring
H U
HU
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D013844:Thiazoles / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D013844:Thiazoles
Die Thiazolidindione--ein neues Therapieprinzip beim Typ-2-Diabetes.