Buformin concentrations in a case of fatal lactic acidosis

Verdonck, LF; Sangster, B.; Heijst, A. N. P. van; Groot, Gerard de; Maes, R. A. A.

doi:10.1007/bf00253815

Cited by 16 publications

(10 citation statements)

References 9 publications

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“…Phenformin and buformin have been withdrawn from use due to high risk of lactic acidosis. 1,2 Although metformin has not been associated with lactic acidosis in otherwise healthy type II diabetics, it has been associated with acute lactic acidosis in patients with heart failure 3 , and compromised pulmonary or renal function 4 . Thus, identification of additional compounds with glucoregulatory properties similar to metformin could be beneficial.…”

mentioning

confidence: 99%

Comparison of antihyperglycemic effects of creatine and metformin in type II diabetic patients

Ročić¹,

Bajuk²,

Ročić³

et al. 2009

CIM

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Clin Invest Med 2009; 32 (6): E322-E326. AbstractPurpose: To compare the antihyperglycemic effects of metformin and creatine in recently detected type II diabetics in a short-term clinical study. Methods: In a 14 day simmetrically randomized crossover study, recently detected type II diabetics received either creatine (2x3 g/day) or metformin (2x500 mg/day) for five days, followed by two days of washout, followed by crossover to the opposite treatment for the next five days. Fasting and post-prandial (-15, 60, 90, 120, 180 and 240 min) blood glucose, insulin, c-peptide, creatine and lactate were measured every other day for the duration of treatment, and HbA1c only at the begining and at the end of the study. Results: Both creatine and metformin decreased glucose concentrations to similar levels at all time points vs. basal glucose values [-15, 60, 90, 120, 180, and 240 min]: 11

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mentioning

confidence: 99%

Comparison of antihyperglycemic effects of creatine and metformin in type II diabetic patients

Ročić¹,

Bajuk²,

Ročić³

et al. 2009

CIM

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“…Similarly, exposure of rat liver mitochondria to high metformin doses (≥ 10 mM) impaired oxidations in the respiratory chain and decreased the membrane potential [13]. The clinical significance of the high concentrations used in these studies remains to be determined since the human plasma concentrations of metformin and buformin rarely exceed 5 mg/L (about 30 µM) [24][25][26][27]. Higher (up to 2-fold) drug concentrations, however, accumulate in the liver [3].…”

Section: Discussionmentioning

confidence: 99%

“…The level of phenformin is much lower (150 µg/L or 0.6 µM) [28]. In this study, the biguanides were investigated at 100 µM and 1.0 mM (several fold higher than therapeutic levels) [24][25][26][27][28].…”

Section: Discussionmentioning

confidence: 99%

Modulation of Cardiomyocyte and Hepatocyte Bioenergetics by Biguanides

Almarzooqi

Alfazari²,

Albawardi³

et al. 2014

J Clin Toxicol

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Biguanides (metformin, buformin and phenformin) have been developed for oral treatment of non-insulindependent diabetes mellitus. Metformin, the drug of choice in this class, controls blood glucose primarily by lowering hepatic gluconeogenesis (e.g., decreasing glucagon-mediated hepatic glucose output). Its mode-of-action, however, is more complex and may involve "refining" cellular bioenergetics (improving energy efficiency) in various cell types including myocytes. Buformin and phenformin presumably have similar mechanisms of action. The main purpose of this in vitro study was to assess the effects of these drugs on bioenergetics-cellular respiration (mitochondrial O 2 consumption) and ATP content-in tissue fragments from the heart muscle (cardiomyocytes) and liver (hepatocytes) of C57BL/6 mice. Cardiomyocyte respiration decreased by 10-26% in the presence of 100 µM metformin (p=0.093), buformin (p=0.028) or phenformin (p=0.015). Similar effects on cardiomyocyte respiration were noted with 1.0 mM drugs. Cardiomyocyte ATP, on the other hand, increased by 17-31% in the presence of 100 µM metformin (p=0.093), buformin (p=0.445) or phenformin (p=0.093). Hepatocyte respiration and ATP decreased by 11-26% and 8-25%, respectively in the presence of 1.0 mM drugs. Decreased respiration and ATP were also noted in hepatocytes exposed to 100 µM metformin for 1 ≤ t ≤ 6 hours (13% and 5%, respectively). Thus, the effects of biguanides on cardiomyocyte bioenergetics differed from that on hepatocyte bioenergetics. These findings suggest that biguanides regulate cardiomyocyte energy conversion, favoring better fuel efficiency (↓respiration/↑ATP). The drug effects in hepatocyte are ↓respiration/↓ATP, favoring less fuel production (↓hepatic gluconeogenesis). Biguanide activities in various tissues may be coupled.

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“…Metformin (1,1-dimethylbiguanide hydrochloride) is an old and widely accepted first-line agent that is anti-hyperglycaemic and improves endothelial dysfunction, hemostasis and oxidative stress, insulin resistance, lipid profiles, and fat redistribution (Rojas & Gomes, 2013). It works in liver and intestine by stopping to release too more glucose (Verdonck et al, 1981). It reduces hepatic glucose output and increases uptake of glucose by the periphery, including skeletal muscle (Bannister & Berlanga, 2016).…”

Section: Metforminmentioning

confidence: 99%

Metformin Is the First Choice of Oral Medicated Breastfeeding Mothers

Mohajan,

Mohajan

2024

IST

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Diabetes mellitus (DM) is a group of metabolic disorders in which there are high levels of glucose in the blood. The effects of DM are long-term damage, dysfunction and failure of various organs. Metformin is a common first-line treatment for type 2 diabetes (T2D) patients. It is one of the oldest treatments for diabetes, dating back to the 1960s. Some scholars in their studies have found that Metformin used by mothers is safe for their breastfeed infants. Most T2D breastfeeding mothers choice Metformin for their initial treatment of diabetes. Sometimes Metformin is found in low levels in the serum of breastfed infants. But no adverse effects are seen when breastfeeding women use Metformin as an oral medication. Although metformin does not lower plasma glucose, it should be used by breastfeeding mothers very carefully and should stop immediately if any side effect is observable.

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Buformin concentrations in a case of fatal lactic acidosis

Cited by 16 publications

References 9 publications

Comparison of antihyperglycemic effects of creatine and metformin in type II diabetic patients

Comparison of antihyperglycemic effects of creatine and metformin in type II diabetic patients

Modulation of Cardiomyocyte and Hepatocyte Bioenergetics by Biguanides

Metformin Is the First Choice of Oral Medicated Breastfeeding Mothers

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