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Rewards Multimedia: Slideshows, Images & Quizzes These observations by Fineman and colleagues (1) are important, because they, for the first time, have demonstrated in humans that metformin effect selectively biased toward gut is actually even stronger than systemic effect where hepatic effect is thought to be dominant and therefore conceptually suggested that gut is the primary site of metformin action. The demonstration is clear and straightforward, and the results may have a great impact not only on our understanding of metformin mechanism in humans but also on future metformin therapy in clinic, for example, using gut-released metformin (Met DR) instead of the current formulation (Met XR). In addition, achieving low plasma exposure of metformin by using Met DR might be particularly useful in patients with conditions that increase the life-threatening risk of metformin-associated lactic acidosis, including renal impairment, cardiac dysfunction, hepatic insufficiency, or intercurrent illness such as dehydration. Despite the strengths discussed here, there are still limitations of their article, as acknowledged by the authors. First, the dose-ranging efficacy trial Fineman and colleagues conducted was short term (12 weeks), although it seems long enough for the article. A longer investigation is still required to test safety, tolerability, and adverse effects of Met DR more sophisticatedly for future clinical application. Second, the mechanism underlying the striking effect of Met DR is unknown. How does gut effect impact the whole body? And is the liver involved in the gut mechanism of metformin? The results obtained by Fineman and colleagues cannot rule out the systemic effect because the bioavailability of Met DR is not zero, despite it being low. In fact, it is conceivable that a certain value of systemic exposure may be essential for metformin action. However, metformin still works even after gut effect is removed by intravenous administration (13), indicating gut exposure could be bypassed for glucose-lowering effect of metformin. Nevertheless, Fineman and colleagues (1) developed a novel gut-release metformin Met DR and demonstrated for the first time that the primary effect of metformin resides in the human gut, at least when orally administrated. Ultimately, these interesting results offered not only a conceptual advance in understanding of metformin mechanism in humans but also the lower gut as a promising target site for future metformin research.
News You Can Use Meetings & Events If extended tablets are used, the starting dose is 500 mg or 1000 mg daily with the evening meal. The dose can be increased by 500 mg weekly up to a maximum dose of 2000 mg except for Fortamet (2500 mg of Fortamet, once daily or in two divided doses). Glumetza tablets (500 -1000mg formulations are given once daily (either 1000 to 2000mg). Fortamet and Glumetza are modified release formulations of metformin. Metformin should be taken with meals.
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