High‐volume continuous venovenous hemodiafiltration plus resin hemoperfusion improves severe metformin‐associated toxicity

Liu, Shuangxin; Xu, Lixia; Ma, Jianchao; Huang, Renwei; Lin, Tzu Chen; Li, Zhuo; Liang, Huabang; Li, Sijia; Li, Ruizhao; Zhang, Li; Tao, Yiming; Li, Zhilian; Chen, Yuanhan; Ye, Zhiming; Zhang, Bin; Wang, Wenjian; Xiao, Houqing; Liang, Xinling; Shi, Wei

doi:10.1111/jdi.12757

Cited by 10 publications

(7 citation statements)

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“…Studies originated from North America, in Europe, in Asia, and in multiple countries spanning between 1991 and 2018. In relationship to our defined outcomes, 14 studies reported the outcome of all-cause mortality [ 22 , 25 – 27 , 29 , 31 , 33 , 37 ], 6 studies reported cardiovascular mortality [ 26 , 27 , 31 , 33 , 37 ], 13 studies reported myocardial ischemia [ 20 , 22 – 24 , 27 – 29 , 31 – 33 , 36 , 37 ], 4 studies reported stroke [ 22 , 31 , 37 ], 5 studies reported hypertension [ 21 , 27 , 30 , 35 ], 5 studies reported peripheral vascular diseases [ 22 , 29 , 31 , 37 ], 4 studies reported heart failure [ 22 , 31 , 37 ], 3 studies reported microvascular events [ 31 , 37 ], 6 studies reported nephropathy [ 21 , 28 , 31 , 34 ], and 2 studies reported oculopathy [ 31 , 33 ].…”

Section: Resultsmentioning

confidence: 99%

“…Pooled analysis of 4 studies (n = 2051) [ 22 , 31 , 37 ] reveals that metformin treatment may not reduce the risk of heart failure (RR: 1.02; 95% CI: 0.0.610, 1.71; P = 0.95) versus control, with a low heterogeneity (I 2 = 0, Additional file 1 : Fig S17). There is also no statistical significance for the effect size of stroke (RR: 0.89; 95% CI: 0.53, 1.47; P = 0.64; I 2 = 7.52%, Additional file 1 : Fig S18) [ 22 , 31 , 37 ], hypertension (RR: 1.54; 95% CI: 0.52, 4.61; P = 0.44; I 2 = 35.94%, Additional file 1 : Fig S19) [ 21 , 27 , 30 , 35 ], and peripheral vascular diseases (RR: 0.98; 95% CI: 0.60, 1.60; P = 0.93; I 2 = 0, Additional file 1 : Fig S20) [ 22 , 29 , 31 , 37 ].…”

Section: Resultsmentioning

confidence: 99%

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Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus

Providência

et al. 2021

Cardiovasc Diabetol

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Background Metformin is a first-line drug in type 2 diabetes mellitus (T2DM) treatment, yet whether metformin may increase all-cause or cardiovascular mortality of T2DM patients remains inconclusive. Methods We searched PubMed and Embase for data extracted from inception to July 14, 2020, with a registration in PROSPERO (CRD42020177283). This study included randomized controlled trials (RCT) assessing the cardiovascular effects of metformin for T2DM. This study is followed by PRISMA and Cochrane guideline. Risk ratio (RR) with 95% CI was pooled across trials by a random-effects model. Primary outcomes include all-cause mortality and cardiovascular mortality. Results We identified 29 studies that randomly assigned patients with 371 all-cause and 227 cardiovascular death events. Compared with untreated T2DM patients, metformin-treated patients was not associated with lower risk of all-cause mortality (RR: 0.98; 95%CI: 0.69–1.38; P = 0.90), cardiovascular mortality (RR: 1.13; 95% CI: 0.60, 2.15; P = 0.70), macrovascular events (RR: 0.87; 95%CI: 0.70–1.07; P = 0.19), heart failure (RR: 1.02; 95% CI:0.61–1.71; P = 0.95), and microvascular events (RR: 0.78; 95% CI:0.54–1.13; P = 0.19). Combination of metformin with another hypoglycemic drug was associated with higher risk of all-cause mortality (RR: 1.49; 95% CI: 1.02, 2.16) and cardiovascular mortality (RR: 2.21; 95% CI: 1.22, 4.00) compared with hypoglycemic drug regimens with no metformin. Conclusion The combination of metformin treatment may impose higher risk in all-cause and cardiovascular mortality. This finding, at least in part, shows no evidence for benefits of metformin in combination in terms of all-cause/cardiovascular mortality and cardiovascular events for T2DM. However, the conclusion shall be explained cautiously considering the limitations from UK Prospective Diabetes Study (UKPDS).

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus

Providência

et al. 2021

Cardiovasc Diabetol

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“…This fact was evidenced in our review, where SLED was used in a few patients (5.4%) for initial RRT. There are a few reports of effective use of resin or charcoal based haem-adsorbent filters in managing patients with severe metformin toxicity[ 43 , 44 ]. However, lack of widespread availability, higher cost, limited data regarding their efficacy and risk of complications especially haemolysis, precludes haemoperfusion (HP) using haemadsorption filters from becoming the modality of choice for ECTR.…”

Section: Discussionmentioning

confidence: 99%

Metformin toxicity: A meta-summary of case reports

Juneja¹,

Nasa²,

Jain³

2022

WJD

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BACKGROUND Metformin is arguably the most commonly prescribed oral hypoglycemic agent for the management of diabetes. Due to the lack of randomized control trials, most of the data pertaining to the clinical course, therapeutic interventions and outcomes of patients with metformin induced toxicity has come from case reports or series. AIM To analyse the symptomology, clinical interventions and outcomes of patients presenting with severe metformin toxicity by reviewing the published case reports and series. METHODS We performed a systematic search from PubMed, Science Direct, Reference Citation Analysis ( ) and Google Scholar databases using the terms “metformin” AND “toxicity” OR “overdose” OR “lactic acidosis” OR “hyperlactatemia”. The inclusion criteria were: (1) Case reports or case series with individual patient details; and (2) Reported toxicity or overdose of metformin in adults, published in the English language. Data regarding baseline demographics, clinical presentation, therapeutic interventions, intensive care unit course and overall outcome were collected. RESULTS Two hundred forty-two individual cases were analysed, from 158 case reports and 26 case series, with a cumulative mortality of 19.8%. 214 (88.4%) patients were diabetics on metformin. 57 (23.6%) had acute ingestion, but a great majority (76.4%) were on metformin in therapeutic doses when they developed toxicity. Metformin associated lactic acidosis (MALA) was the most commonly reported adverse effect present in 224 (92.6%) patients. Most of the patients presented with gastrointestinal and neurological symptoms and a significant number of patients had severe metabolic acidosis and hyperlactatemia. The organ support used was renal replacement therapy (RRT) (68.6%), vaso-pressors (58.7%) and invasive mechanical ventilation (52.9%). A majority of patients (68.6%) received RRT for toxin removal, renal dysfunction and correction of MALA. Patients with lowest pH and highest serum lactate and metformin levels also had favourable outcomes with use of RRT. CONCLUSION Most of the reported cases were on therapeutic doses of metformin but developed toxicity after an acute deterioration in renal functions. These patients may develop severe lactic acidosis, leading to significant morbidity and need for organ support. Despite severe MALA and the need for multiple organ support, they may have good outcomes, especially when RRT is used. The dose of metformin, serum pH, lactate and metformin levels may indicate the severity of toxicity and the need for aggressive therapeutic measures but may not necessarily indicate poor outcomes.

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“…In addition to the discussion above, metformin has a large volume of distribution, so early RRT may be beneficial before the substance distributes throughout the body and tissues [12]. As metformin metabolites cause a severe increase in lactic acid, mortality soars.…”

Section: Discussionmentioning

confidence: 99%

Profound Metabolic Acidosis due to Metformin Intoxication Requiring Dialysis

Hermez

Dudash-Mion

2021

Case Reports in Nephrology

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Metformin-associated lactic acidosis (MALA) is a rare but life-threatening condition with often high mortality rates. Despite this, metformin continues to be one of the most commonly prescribed antihyperglycemic agents in the market. We present a unique case of a 61-year-old female with severe acidosis of pH = 6.72 and lactic acid of 26 mmol/L who presented obtunded after ingestion of an unknown amount of metformin. She was subsequently intubated, became hypotensive, and was initiated on vasopressors. She was swiftly started on a combination of intermittent hemodialysis (IHD) and bicarbonate therapy 7 hours after admission followed by continuous renal replacement therapy (CRRT) as she became more hemodynamically unstable. The patient’s renal function improved, and she was discharged 7 days after admission with favorable sequelae. Dialysis is often reported in cases of severe MALA; however, it remains unclear how quickly dialysis should be initiated. This case aims to explore the benefits of quick initiation of extracorporeal measures in the forms of IHD and CRRT with concurrent bicarbonate supplementation. Furthermore, this case demonstrates the importance of clinical suspicion in metabolic acidosis in a patient on metformin therapy.

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High‐volume continuous venovenous hemodiafiltration plus resin hemoperfusion improves severe metformin‐associated toxicity

Cited by 10 publications

References 15 publications

Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus

Association of metformin monotherapy or combined therapy with cardiovascular risks in patients with type 2 diabetes mellitus

Metformin toxicity: A meta-summary of case reports

Profound Metabolic Acidosis due to Metformin Intoxication Requiring Dialysis

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