Metformin-associated lactic acidosis in an intensive care unit

Peters, N.; Jay, Nicolas; Barraud, Damien; Cravoisy, Aurélie; Nace, Lionel; Bollaert, Pierre‐Édouard; Gibot, Sébastien

doi:10.1186/cc7137

Cited by 134 publications

(158 citation statements)

References 18 publications

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“…With typical metformin use, the incidence of MALA is very low (,10 cases per 100,000 patient-years) (15,35,36). MALA events that are reported are usually associated with an elevated metformin dose or plasma exposure and an intercurrent event that further disrupts lactate production or clearance, such as sepsis, reduced tissue perfusion, anoxia, or impaired hepatic metabolism (15,22,(36)(37)(38)(39). Optimization of the presystemic gut-restricted metformin mechanisms of action may yield a significant treatment advantage by lowering the risk of MALA, particularly in at-risk populations.…”

Section: Resultsmentioning

confidence: 99%

The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies

et al. 2015

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OBJECTIVEDelayed-release metformin (Met DR) is formulated to deliver the drug to the lower bowel to leverage the gut-based mechanisms of metformin action with lower plasma exposure. Met DR was assessed in two studies. Study 1 compared the bioavailability of single daily doses of Met DR to currently available immediaterelease metformin (Met IR) and extended-release metformin (Met XR) in otherwise healthy volunteers. Study 2 assessed glycemic control in subjects with type 2 diabetes (T2DM) over 12 weeks. RESEARCH DESIGN AND METHODSStudy 1 was a phase 1, randomized, four-period crossover study in 20 subjects. Study 2 was a 12-week, phase 2, multicenter, placebo-controlled, dose-ranging study in 240 subjects with T2DM randomized to receive Met DR 600, 800, or 1,000 mg administered once daily; blinded placebo; or unblinded Met XR 1,000 or 2,000 mg (reference). RESULTSThe bioavailability of 1,000 mg Met DR b.i.d. was ∼50% that of Met IR and Met XR (study 1). In study 2, 600, 800, and 1,000 mg Met DR q.d. produced statistically significant, clinically relevant, and sustained reductions in fasting plasma glucose (FPG) levels over 12 weeks compared with placebo, with an ∼40% increase in potency compared with Met XR. The placebo-subtracted changes from baseline in HbA 1c level at 12 weeks were consistent with changes in FPG levels. All treatments were generally well tolerated, and adverse events were consistent with Glucophage/Glucophage XR prescribing information. CONCLUSIONSDissociation of the glycemic effect from plasma exposure with gut-restricted Met DR provides strong evidence for a predominantly lower bowel-mediated mechanism of metformin action.

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Section: Resultsmentioning

confidence: 99%

The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies

et al. 2015

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“…Th e estimated incidence is 6 cases per 100,000 patient-years (9). Th e presence of metformin-associated hyperlactatemia in critical care patients has been associated with a mortality >30% (10).…”

Section: Discussionmentioning

confidence: 99%

Metformin-Induced Lactic Acidosis with Emphasis on the Anion Gap

Blough¹,

Moreland²,

Mora³

2015

Baylor University Medical Center Proceedings

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“…MALA in ICU setting has a 30% mortality rate [27]. However, these figures are better than what the pH and lactate levels would predict [28,29].…”

Section: Discussionmentioning

confidence: 94%

Lactic Acidosis in a Man with Diabetes: Is Metformin the Culprit?

Dissanayake¹,

Wijewickrama²,

Katulanda³

2017

J Diabetes Metab

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Background: Lactic acidosis is a rare but serious adverse effect of metformin, particularly when used in high doses in patient with other risk factors. We report a case of metformin associated lactic acidosis that improved with hemodialysis.Case presentation: Seventy-year-old male with diabetes and stage IV chronic kidney disease presented with vomiting and was found to have lactic acidosis with lactate of 8 mmol/L while being on metformin 1 g thrice daily. He was successfully managed with haemodialysis and supportive care. Conclusion:This case illustrates the importance of judicious drug prescription in patients with multiple comorbidities; need to consider metformin induced lactic acidosis in appropriate settings and importance of active management with haemodialysis. Recommendations on prevention and options for treatment are also be discussed.

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Metformin-associated lactic acidosis in an intensive care unit

Cited by 134 publications

References 18 publications

The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies

The Primary Glucose-Lowering Effect of Metformin Resides in the Gut, Not the Circulation: Results From Short-term Pharmacokinetic and 12-Week Dose-Ranging Studies

Metformin-Induced Lactic Acidosis with Emphasis on the Anion Gap

Lactic Acidosis in a Man with Diabetes: Is Metformin the Culprit?

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