Possible synergistic effect of metformin and enalapril on the development of hyperkaliemic lactic acidosis

Franzetti, Ivano; Donnini, P; Gaiazzi, M; Emanuela, Mazzola; Zibetti, Elisabetta; Uccella, R

doi:10.1016/s0168-8227(97)00098-3

Cited by 17 publications

(10 citation statements)

References 11 publications

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“…These diseases constitute risk factors for renal failure in diabetic patients and hence increase the risk of development of metformin induced lactic acidosis (MALA). Furthermore, combination of ACEI and metformin has been reported to have a possible synergistic effect on the development of hyperkalaemic lactic acidosis [19]. Non-steroidal anti-inflammatory drugs (NSAIDs) are also well known to precipitate acute renal failure, particularly in the elderly and susceptible individuals.…”

Section: Discussionmentioning

confidence: 99%

Contraindications to metformin therapy among patients with type 2 diabetes mellitus

Sweileh

2007

Pharm World Sci

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Section: Discussionmentioning

confidence: 99%

Contraindications to metformin therapy among patients with type 2 diabetes mellitus

Sweileh

2007

Pharm World Sci

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“…We did not, in contrast to a previous study of type 2 diabetic patients in which systolic blood pressure and plasma lactate concentration correlated significantly [23], find a relationship between blood pressure and plasma lactate, nor did we observe independent associations with CHD, renal function, or use of either ACE inhibitors or NSAIDs. These findings, although reassuring, do not rule out the possibility that metformin treatment may, in certain clinical states such as cardiac failure and renal insufficiency [6], increase the risk of lactic acidosis, especially in the presence of potentially nephrotoxic drugs [11, 12]. However, available epidemiological evidence suggests that such situations are relatively rare [6–8].…”

Section: Discussionmentioning

confidence: 99%

“…Although up to 50% of patients receiving metformin in the UK have at least one contra‐indication to its use [9, 10], the incidence of lactic acidosis in these patients appears very low [10]. Both nonsteroidal anti‐inflammatory drugs (NSAIDs) [11] and angiotensin converting enzyme (ACE) inhibitors [12] may increase the risk of lactic acidosis in nephropathic patients treated with metformin, but reports of these interactions have been confined to single cases.…”

Section: Introductionmentioning

confidence: 99%

The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: The Fremantle Diabetes Study

Davis

Jackson

Davis

et al. 2001

Brit J Clinical Pharma

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Aims To determine (i) which factors, including metformin, are associated with the fasting plasma lactate concentration in type 2 diabetes, and (ii) whether plasma lactate is associated with haemodynamic and metabolic effects. Methods We measured fasting plasma lactate in 272 well-characterized diabetic patients from a community-based sample, 181 (67%) of whom were taking metformin with or without other therapies. Linear regression analysis was used to identify predictors, including metformin therapy, of the plasma lactate, and to investigate associations between plasma lactate and resting pulse rate and serum bicarbonate. Factor analysis assessed independent relationships between groups of cosegregating variables.Results Metformin-treated patients had higher plasma lactate concentrations than nonmetformin-treated subjects (geometric mean [s.d. range] 1.86 [1.34±2.59] vs 1.58 [1.09±2.30] mmol l x1 , respectively; P<0.001). In a linear regression model, plasma glucose, BMI and metformin use (but not dose) were independently associated with plasma lactate (Pj0.028); after adjustment for the former two variables, metformintreated patients had a mean plasma lactate 0.16 mmol l x1 greater than in subjects not taking the drug. Factor analysis revealed that plasma lactate, plasma glucose, BMI and pulse rate cosegregated but serum bicarbonate was not in this grouping. Conclusions The present results show that metformin therapy increases the fasting plasma lactate in ambulant patients with type 2 diabetes from a community-based cohort. From associations in the data we hypothesize that this increase re¯ects (i) increased sympathetic activity in patients with the metabolic syndrome (ii) increased substrate (glucose) availability and (iii) a direct metformin effect.

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“…8 Fatores não relacionados diretamente com o tratamento da diabetes mellitus, como o peso corporal, a pressão arterial, a glicemia, a função renal e a utilização de anti--inflamatórios não esteróides ou de inibidores da enzima de conversão da angiotensina também parecem influenciar os níveis de lactatos. [9][10][11] Existe, assim, alguma controvérsia na afirmação de que a utilização de metformina per si, condiciona um aumento dos níveis de lactato sérico nos doentes diabéticos.…”

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Relação entre o Tratamento com Metformina e o Desenvolvimento de Hiperlactacidemia no Serviço de Urgência

2014

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RESUMOIntrodução: Em diabéticos tipo 2 sob metformina o desenvolvimento de hiperlactacidemia ou mesmo acidose láctica parece decorrer de um evento precipitante agudo. Este estudo objetiva avaliar a prevalência e risco relativo de hiperlactacidemia em diabéticos observados no Serviço de Urgência, os fatores preditores da concentração de lactatos e a influência da lactacidémia no prognóstico. Resultados:A concentração de lactatos e proporção de hiperlactacidemia foram significativamente superiores nos diabéticos (2,1 ± 0,1 mmol/L vs 1,1 ± 0,1mmol/L, p < 0,001 e 39,1% vs 3,6%, p < 0,001, respetivamente); particularmente naqueles sob metformina comparativamente aos restantes diabéticos (2,7 ± 0,2 mmol/L vs 1,6 ± 0,1 mmol/L, p < 0,001 e 56,9 % vs 23,3 %, p < 0,001, respetivamente). Os diabéticos sob metformina contabilizaram uma probabilidade de hiperlactacidemia 25x superior (OR = 25,10, p < 0,05). A creatinina representou o único fator preditor independente da lactacidemia (B = 1,33; p < 0,05). Os doentes com hiperlactacidemia apresentaram probabilidade 4,4x superior de serem internados ou falecerem (OR = 4,37, p < 0,05). E, quando internados, contabilizaram tempo de internamento (21,66 ± 5,86 dias vs 13,68 ± 5,33dias, p < 0,001) e número de óbitos superiores (12,5% (n = 4) vs 4,3% (n = 2), p < 0,05). Conclusões: Demonstrou-se um risco acrescido de hiperlactacidemia em diabéticos tipo 2, particularmente naqueles sob metformina. A creatinina sérica representou o único fator preditor independente da concentração de lactatos. A presença de hiperlactacidemia condicionou um pior prognóstico. Palavras-chave: Diabetes Mellitus Tipo 2; Metformina; Hiperlactacidemia; Portugal; Serviço de Urgência. ABSTRACTIntroduction: In type 2 diabetic patients treated with metformin the development of hyperlactacidemia or even lactic acidosis seems to result from an acute precipitating event. This study aims to assess the prevalence and relative risk of hyperlactacidemia in diabetic patients admitted in the Emergency Room, the predictive factors for high lactate concentration and the influence of hyperlactacidemia in patients' prognosis. Material and Methods:Transversal observational study including patients observed between June and October 2012: 138 type 2 diabetics, 66 treated with metformin, and 83 non-diabetic patients. Studies' variables: age, sex, cause of admition, blood pressure, drugs, personal history, analytical study (biochemistry and arterial blood gas analyses with lactate) and destination. Statistical analysis was performed using SPSS 21.0 ® . Results:Mean lactate concentration and hyperlactacidemia prevalence were significantly higher in diabetic patients (2.1 ± 0.1mmol/L vs 1.1 ± 0.1mmol/L, p < 0.001 and 39.1% vs 3.6%, p < 0.001, respectively) and in those under metformin compared to other diabetics (2.7 ± 0.2 mmol/L vs 1.6 ± 0.1 mmol/L, p < 0.001 and 56.9% vs 23.3%, p < 0.001, respectively). Diabetics on metformin presented a 25-fold increased risk of hyperlactacidemia (OR = 25.10, p < 0.05). Creatinine was the only i...

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Possible synergistic effect of metformin and enalapril on the development of hyperkaliemic lactic acidosis

Cited by 17 publications

References 11 publications

Contraindications to metformin therapy among patients with type 2 diabetes mellitus

Contraindications to metformin therapy among patients with type 2 diabetes mellitus

The relationship between metformin therapy and the fasting plasma lactate in type 2 diabetes: The Fremantle Diabetes Study

Relação entre o Tratamento com Metformina e o Desenvolvimento de Hiperlactacidemia no Serviço de Urgência

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