Metformin associated lactic acidosis

Fitzgerald, Emma; Mathieu, S.; Ball, Andrew J.

doi:10.1136/bmj.b3660

Cited by 32 publications

(29 citation statements)

References 8 publications

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“…It has a reported mortality rate of 30-50%. 7,8 The main identifiable risk factors for mortality are sepsis, acute cardiovascular events and end-stage hepatic failure. However, we observed that metformin ingestion caused lactic acidosis in two subjects without any precipitating factors before taking massive overdose of this drug.…”

Section: Discussionmentioning

confidence: 99%

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Massive Metformin Overdose in Two Subjects with Suicidal Behavior: Brief Communication

Arıkan¹,

Tuzcu²,

Bahçeci³

et al. 2012

Turkiye Klinikleri J Med Sci

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Section: Discussionmentioning

confidence: 99%

“…8,11 Hemodialysis should systematically be performed in more severe forms of lactic acidosis which deteriorate despite intravenous bicarbonate therapy. 12,13 In the conclusion, metformin intoxication with suicidal intention may lead to metabolic acidosis with a high anion gap.…”

Section: Discussionmentioning

confidence: 99%

Massive Metformin Overdose in Two Subjects with Suicidal Behavior: Brief Communication

Arıkan¹,

Tuzcu²,

Bahçeci³

et al. 2012

Turkiye Klinikleri J Med Sci

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“…While these small molecular differences may explain a decreased risk of lactic acidosis with metformin [1], do they suffice to explain the only favourable results observed in the UKPDS34 subgroup If metformin were to be lacking in effectiveness, this would be extremely detrimental for all the type 2 diabetes patients to whom it has been administered as the first-line pharmacological treatment [2]. It could be responsible for serious adverse reactions such as lactic acidosis, especially in the event of acute renal insufficiency [21] and vitamin B12 deficiency, as was clearly shown in the HOME study [22].…”

Section: What Are We To Think Of These Data?mentioning

confidence: 99%

Metformin in type 2 diabetes: where is the evidence?

Boussageon¹

2016

J Diabetol Endocrinol.

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Taking into consideration the main evidence available in 2015, Boussageon contest the status of metformin as the first -line treatment for DT2 patients. He contends that as regards macrovascular and microvascular complications, its efficacy has never been proven in a double-blind RCT. This observation leads to a more general interrogation on how anti-diabetes medication is to be assessed. Key messagesEver since the results of the UK Prospective Diabetes Study (UKPDS) 34 were published in 1998, metformin has been considered as the first-line pharmacological treatment for type 2 diabetes.However, from several standpoints the UKPDS was methodologically questionable. The effectiveness of metformin with regard to microvascular and macrovascular complications has never been proven in a randomized double-blind placebo-controlled clinical trial.And upon analysis of published randomized clinical trials taken as a whole, it becomes increasingly apparent that the effectiveness of metformin has not been proven, even when microvascular complications are involved.This observation leads to a more general interrogation on the fact that assessment of the clinical benefits of antidiabetic medication in general is presently lacking. Has the effectiveness of metformin actually been proven?Metformin is an oral antidiabetic drug (OAD) in the biguanide class [1]. It is the recommended first-line treatment for type 2 diabetes (DT2) patients [2]. Its efficacy was supposedly conclusively demonstrated in the UKPDS 34 study published in 1998 (reduction in mortality: RR0.64; CI 95% (0.45 to 0.91) and in myocardial infarction: RR0.61; CI 95% (0.41 to 0.89) [3]. However, these rather impressive results regarding total 10 year mortality (ARR0.07; NNT14) in a small subgroup of obese type 2 diabetes patients (342 in the metformin group vs. 411 patients in the conventional group) have never been reproduced [4]. For instance, the home study [5] years of follow-up, no statistically significant difference was found for total mortality: RR1.48; CI 95% (0.54 to 4.09) or for IDM: RR0.99; CI 95% (0.25 to 3.90). Taking into account all the other randomized clinical trials (RCTs) having evaluated the specific effectiveness of metformin in DT2 patients [6], it becomes evident that metformin has not significantly modified total mortality: RR0.99; CI 95% (0.75 to 1.31), cardiovascular mortality: RR  1.05; CI 95% (0.67 to 1.64), IDM occurrence: RR0.90; CI95% (0.74 to 1.09), cerebrovascular accidents: RR0.76; CI95% (0.51 to 1.14), cardiac insufficiency: RR1.03; CI 95% (0.67 to 1.59), peripheral vascular events: RR0.90; CI 95% (0.46 to 1.78), lower limb amputations: RR1.04; CI 95% (0.44 to 2.44) or microvascular complications: RR0.83; CI95% (0.59 to 1.17). Once an analysis without selection bias has been carried out, it becomes apparent that on the basis of clinical criteria, the efficacy of metformin has not been proven; in science, the reproducibility of results remains an essential validity criterion. The dark side of UKPDSIn point of fact, t...

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“…Since 1995, metformin has been a widely prescribed glucose lowering agent in the United States for type 2 diabetic and polycystic ovary syndrome patients. It is a welltolerated drug with lactic acidosis as a reported serious side effect [86]. However, the link between lactic acidosis and metformin use has recently been questioned [87].…”

Section: Metformin As a Glucose Lowering Drugmentioning

confidence: 99%