Lege Artis Medicinae

[Metformin - but what else is in the box?]

KISS Zsófia1, KIS János Tibor1

APRIL 22, 2011

Lege Artis Medicinae - 2011;21(04)

[Metformin is currentlly the most commonly prescribed oral antidiabetic drug for the treatment of patients with type 2 diabetes mellitus. Its administration is limited by the contraindications and the possible gastrointestinal side effects. In Hungary, metformin is currently available in numerous forms, among which the extended-release tablets are distinguished because of their tolerability. The authors summarise the most recent data about the favourable features of metformin, help clinicians to choose the appropriate preparation of metformin, and highlight the administration procedures that help to avoid gastrointestinal side effects.]

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  1. Budai Irgalmasrendi Kórház Kht.

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[Halogen addition and steroid effect]

NAGY Nikoletta, KEMÉNY Lajos

[Among locally administered anti-inflammatory drugs used in dermatology, steroids are among the most commonly applied ones. In everyday practice, choosing the right local steroid preparation is not easy, since more than 50 different local steroid preparations with at least 30 different active ingredients are available. The choice of the local steroid preparation depends on a number of aspescts. It is recommended to apply local steroid preparations that, besides having a strong effect, also have favourable side effect profiles. Moreover, it is subservient to apply local steroids that penetrate deeply into the skin, but have minimal systemic absorption, therefore do not inhibit significantly the hypothalamicpituitary- adrenal axis if administered locally. These characteristics of local steroid preparations are determined by chemical modifications at various positions on the steroid-frame. In this study, we examined the different types of chemical modifications, and the relationship between halogen addition and the characteristics of steroid preparations. We compared the local steroid preparations using the data of previous clinical trials. Regarding the efficacy, safety, tolerability and the risk/benefit ratio, the halogenated steroid preparations were overall superior to nonhalogeneted ones. Among the halogenated preparations, the fluticasone propionate, the mometasone furoate and clobetasol propionate were proved to be the most suitable locally administered, very potent or super potent ones.]

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[Cardiovascular risk of non-steroidal antiinflammatory drugs]

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[During the past decade, a number of original publications, reviews and metaanalyses were published on the cardiovascular safety of nonsteroidal antiinflammatory drugs (NSAIDs). As this group of medicines is among the most frequently used ones and many preparations are available over the counter, it seems to be prudent to summarise the most important results on the safety of these drugs, and underline their potentially harmful cardiovascular side effects. Nevertheless, it can also be emphasized that there are substantial differences between different compounds, and the cardiovascular risk does not depend on the ratio of COX-1/COX-2 selectivity. Cardiovascular risk can be increased by all NSAIDs with the possible exception of naproxen.]

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[IgG4-related disease]

ZEHER Margit

[IgG-4-related disease is a clinical entity characterised by significant elevation in serum IgG-4 levels, infiltration of IgG-4+ plasma cells into the involved tissues, enhanced fibrosis, and good therapeutic response to corticosteroids. The IgG-4 associated disease mostly affects two organs. The salivary and lacrimal gland enlargement and inflammation is known as Mikulicz’s disease, which had been previously known as a subtype of Sjögren’s syndrome for a long time. The other commonly involved organ is the pancreas, in which a special form of chronic pancreatitis, namely autoimmune pancreatitis develops. IgG-4 associated disease as a separate disease has been suggested by Japanese authors. Previously published data support the common pathogenesis of autoimmune pancreatitis and Mikulicz’s disease. Besides these two manifestations, similar histological lesions and elevated IgG-4 levels have been demonstrated in many other organs. At present, it is not clearly demonstrated whether IgG-4 syndrome is an autoimmune disorder, and we do not know the exact reason of the elevated IgG-4 levels in patients with this syndrome. IgG-4 is a regulatory immunoglobulin, the main function of which is to decelerate immune responses, thus its pathologic role in tissue destruction is difficult to explain. It is not clear either, whether IgG-4 syndrome is indeed a single disease, or only an example of overlapping symptoms of various diseases. On the basis of the characteristic histological lesions in various organs, IgG-4 syndrome is similar to multi-organ diseases, such as sarcoidosis or vasculitis.]

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[METFORMIN - BUT WHAT ELSE IS IN THE BOX?]

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[Metformin is currentlly the most commonly prescribed oral antidiabetic drug for the treatment of patients with type 2 diabetes mellitus. Its administration is limited by the contraindications and the possible gastrointestinal side effects. In Hungary, metformin is currently available in numerous forms, among which the extended-release tablets are distinguished because of their tolerability. The authors summarise the most recent data about the favourable features of metformin, help clinicians to choose the appropriate preparation of metformin, and highlight the administration procedures that help to avoid gastrointestinal side effects.]

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[Type 2 diabetes has become a global public health problem, threatening the economies of all nations, as a consequence of rapid urbanisation, changing eating habits, sedentary lifestyle and obesity. Asian populations tend to develop diabetes at younger ages and lower body mass index compared with Caucasians. The latest guidelines of the American Diabetes Association and the European Association for the Study of Diabetes recommend lifestyle interventions as the first step for patients with newly diagnosed type 2 diabetes. The widely used metformin remains one of the first-line drugs for type 2 diabetes. If monotherapy alone does not achieve or maintain the target HbA1c level, addition of a second oral agent is recommended as a second step. The highly selective dipetidyl peptidase-4 inhibitor sitagliptin and metformin are efficient and well tolerable. The complementary effects of sitagliptin and metformin lead to an efficient, safe and long-term improvement in glycaemic control.]

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[THE ROLE AND METHODS OF IMPROVING INSULIN SENSITIVITY AND BETA-CELL FUNCTION IN TYPE 2 DIABETES]

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[Increased knowledge on the pathogenesis of type 2 diabetes has considerably transformed the principles and practice of treatment. Insulin resistance and beta-cell dysfunction, the two main components of the pathogenesis both play a role in the conversion of normal glucose metabolism, through impaired glucose tolerance, into type 2 diabetes. Decreased insulin sensitivity, with or without beta-cell dysfunction, is present in the vast majority cases, therefore, its treatment is essential. Physical activity is known to improve insulin sensitivity. The primary action of the recommended first-line pharmacological agent metformin is the inhibition of hepatic glucose production but it also moderately stimulates muscle glucose uptake. Glitazones are insulin sensitizers that increase glucose uptake in muscle and adipose tissue and moderately decrease hepatic glucose production. Some evidence suggests that α-glucosidase inhibitors and also certain insulin secretagogues can improve the effect of insulin. Early detection of the pathologic state and an efficient treatment to improve both insulin sensitivity and beta-cell function are essential in order to slow the progression and prevent the development of complications in type 2 diabetes.]

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[The role of metformin in the glucose-lowering therapy of patients with type 2 diabetes]

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[Metformin is the oral antidiabetic drug of choice for patients with type 2 diabetes. Its effect is predominantly based on the reduction of insulin resistance by inhibiting hepatic glucose production. Metformin can be used as an initial oral antidiabetic drug at the start of, or in case of the failure of lifestyle modifications. Metformin is also used in dual or triple oral antidiabetic combinations, however, its use should not be suspended even if initiation of insulin therapy is indicated in patients with type 2 diabetes. Metformin does not increase bodyweight and the risk of hypoglycaemia, and recent data suggest that it decreases the risk of tumour development. Today, an extended- release (XR) formulation is also available besides the traditional one, which not only simplifies the treatment, but might also reduce the incidence of gastrointestinal adverse effects.]