PHARMACEUTICAL COMBINATIONS FOR TREATMENT AND PREVENTION OF DIABETES MELLITUS

Pharmaceutical combinations for treatment and/or prevention of all sorts, periods and complications of diabetes mellitus in mammals, thus including the pre-diabetic diseases and their complications, optionally including furthermore ischaemic heart disease comprising an effective dose of at least one enzymatic nitric oxide (NO) donor active ingredient and optionally comprising an effective dose of at least one antidiabetic active ingredient, and further optionally comprising usual pharmaceutically acceptable carriers and/or other auxiliaries. The combination may consist of more than one pharmaceutical compositions. The effective doses related to the new insulin-sensitizing effect are considerably lower than the usual doses related to the known effect of most active substances dues to metabolic effects that influence insulin sensitivity in healthy and insulin resistant mammals. The usual dose of NO-donors is necessary when the patient has also ischaemic heart disease. Preferred antidiabetics include insulin, a thiazolidinedion, a biguanide derivative, an alpha -glucosidase-inhibitor, an alpha 2-adrenergic-antagonist and/or a sulphonamide, preferably a sulphonylurea. Preferred enzymatic NO donors are nitroglycerin, racemic isosorbide monoitrate, and/or its stereroizomers, racemic isosorbide dinitrate and/or its stereoizomers, erythrityl tetranitrate, pentaerythritol-tetranitrate, methylpropyl-propanediol-dinitrate, propatyl nitrate, trolnitrate, tenitramine and/or nicorandile. The invention includes methods of treatment and processes to prepare the compositions. L'invention concerne des combinaisons pharmaceutiques permettant de traiter et/ou de prévenir toutes sortes d'épisodes et de complications des diabètes mellitus chez les mammifères, notamment les maladies pré-diabétiques et leur complications, et éventuellement la cardiopathie ischémique. Ces combinaisons pharmaceutiques comprennent une dose efficace d'au moins un ingrédient actif donneur d'oxyde nitrique (NO) enzymatique, éventuellement au moins ingrédient actif antidiabétique, et éventuellement des excipients pharmaceutiquement acceptables usuels et/ou d'autres auxiliaires. Ces combinaisons sont constituées de plus d'une composition pharmaceutique. Les doses efficaces associées au nouvel effet de sensibilisation à l'insuline sont considérablement inférieures aux doses habituelles associées à l'effet connu de la plupart des substances active, du fait des effets métaboliques qui influencent la sensibi