Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus

Salpeter, Shelley R.; Greyber, Elizabeth; Pasternak, Gary A; Salpeter, E. E.

doi:10.1002/14651858.cd002967.pub2

Cited by 362 publications

(440 citation statements)

References 269 publications

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“…In patients with type 2 diabetes, the reported incidence of LA is similar in patients who are taking metformin and in those who have never taken it, when risk factors for LA have been excluded 8. Mortality in patients with metformin-attributed LA seems to be ∼40% and also seems to be associated with heart failure.…”

Section: The Risks Of Continuingmentioning

confidence: 91%

Metformin: safety in cardiac patients

Khurana

Malik

2010

Postgraduate Medical Journal

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Metformin is a biguanide, insulin sensitiser that reduces blood sugar levels. There are concerns about the risk of lactic acidosis in patients receiving metformin who have procedures requiring iodinated contrast, and in those with renal impairment or heart failure. The data on which these concerns are based are reviewed, with the conclusion that metformin treatment is rarely to blame for lactic acidosis. A generic policy of stopping metformin 48 h before and 48 h after the procedure in all patients is counterintuitive, lacks any evidence base and does not conform to the principles of best practice. In patients with heart failure, although the underlying condition can predispose to lactic acidosis, existing evidence suggests that metformin use is associated with improved outcome rather than increased risk.

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Section: The Risks Of Continuingmentioning

confidence: 91%

Metformin: safety in cardiac patients

Khurana

Malik

2010

Postgraduate Medical Journal

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“…A Coch rane meta-analysis conducted on 47 096 patients with a follow-up of 86 067 patient-years compared the incidence of LA in patients who received MF with those who did not, irrespective of the eGFR. [14] They found that for the upper limit of 95% confidence the true incidence of LA was 6.3/100 000 patient-years for the MF group and 7.8/100 000 patient-years for the non-MF group.…”

Section: Cmementioning

confidence: 96%

Recent important strategies in the management of chronic kidney disease

Meyers

Davies

2017

S Afr Med J

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The burden of chronic kidney disease (CKD) is considerably higher in low-and middle-income countries, which are less able than the developed world to cope with treating advanced renal failure owing to financial constraints. Prevention, early diagnosis and implementation of existing knowledge can improve outcomes. This review presents several recent advances to assist with avoiding and slowing down CKD progression and reducing common comorbid complications. The following are discussed: the possible use of metformin in patients with type 2 diabetes-related CKD; recent inexpensive important developments in the treatment of autosomal-dominant polycystic kidney disease; prevention of acidosis and the early dietary reduction of red meat consumption; and the therapeutic lowering of uric acid in persistent hyperuricaemia. Finally, an active and monitored exercise programme should be undertaken whenever possible. All of these recommendations have been shown to significantly slow the progression of CKD and increase cardiovascular protection. CME 731September 2017, Vol. 107, No. 9 CME addition to the multiple cardiovascular and renal complications of DM, renal dysfunction in the elderly is further compounded by the slow but progressive fall in glomerular filtration rate (GFR) in persons >45 years of age (i.e. ±1 mL/min/year) and also because people live longer. For many years the US Food and Drug Administration (FDA), the Regulatory Cooperation Council (RCC) in Canada and other regulatory bodies have indicated that the use of MF is contraindicated in patients with mild and moderate CKD (stages 3a and 3b) owing to the rarely reported but life-threatening complication of lactic acidosis (LA) (serum lactate levels ≥15 mmol/L).That LA does not occur in patients who receive MF, with an estimated GFR (eGFR) of 50 -30 mL/min., has been indicated in studies conducted by Inzucchi et al. [13] They showed that MF can be safely used in these patients, provided that certain guidelines are always followed. A Coch rane meta-analysis conducted on 47 096 patients with a follow-up of 86 067 patient-years compared the incidence of LA in patients who received MF with those who did not, irrespective of the eGFR.[14] They found that for the upper limit of 95% confidence the true incidence of LA was 6.3/100 000 patient-years for the MF group and 7.8/100 000 patient-years for the non-MF group.It is important to remember that before prescribing MF for any degree of renal function, certain rules are essential and must be fully adhered to. As many practitioners are either unaware or uncertain of the predisposing conditions, these are set out in Table 4.Mechanisms of MF-associated LA are not well elucidated, but include conversion of glucose to lactate in the splanchnic bed and inhibition of hepatic gluconeogenesis (i.e. from lactate, pyruvate and adenine). [15,16] It is essential that any patient with the abovementioned precipi ta ting disorders is instructed to immediately but temporarily withdraw the use of MF and present to a doctor. Patients h...

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“…In their specific study, Masoudi et al demonstrated lower prevalence of lactic acidosis in patients on metformin as compared with control group (2.3% vs. 2.6%) 26 . In a systematic Cochrane analysis of 347 prospective comparator and observational cohort studies, the prevalence of lactic acidosis in metformin treated patients was 4.3/100,000 patients versus 5.4/100,000 patients in the non-metformin group 27 . The risk of lactic acidosis is increased in patients with impaired renal function and estimated glomerular filtration rate (eGFR) <50, and metformin should be avoided at eGFR <30.…”

Section: Metforminmentioning

confidence: 99%

“…pokazali su da je učestalost laktične acidoze u bolesnika koji uzimaju metformin bila manja (2,3 %) nego u kontrolnoj skupini (2,6 %) 26 . U sustavnoj Cochrane analizi 347 prospektivnih, komparativnih i opservacijskih kohortnih studija, učestalost laktične acidoze u bolesnika liječenih metforminom bila je 4,3/100 000 bolesnika, a u nemetforminskoj skupini 5,4/100 000 27 . Rizik od laktične acidoze raste u bolesnika s ošteće-nom bubrežnom funkcijom i eGFR-om < 50, a kod eGFR-a < 30 metformin treba izbjegavati.…”

Section: Sulfonylureas and Meglitinidesunclassified

Cardiovascular Safety of Oral Antidiabetic Drugs.

et al. 2016

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ORCID: Luka Zaputović, http://orcid.org/0000-0001-9415-9618 • Željka Rubeša Miculinić, http://orcid.org/0000-0002-1880-1493 Sanja Matijević Rončević, http://orcid.org/0000-0003-0627-2114 • David Gobić, http://orcid.org/0000-0001-9406-1127 Teodora Zaninović Jurjević, http://orcid.org/0000-0001-8359-3910 SAŽETAK: Hrvatska pripada skupini europskih zemalja s visokim kardiovaskularnim rizikom i rastućom prevalencijom šećerne bolesti tipa 2 (DMT2). Prema podatcima Nacionalnog registra osoba sa še-ćernom bolešću (CroDiab registar), u Hrvatskoj je 2014. godine bilo evidentirano ukupno 254 296 osoba oboljelih od dijabetesa starijih od 18 godina (7,9 %). DMT2 je, uz hipertenziju i hiperlipidemiju, jedan od vodećih čimbenika kardiovaskularnog rizika. Glavne regulatorne agencije za lijekove, potaknute štetnim kardiovaskularnim učincima rosiglitazona u RECORD studiji i kasnijim metaanalizama, zahtijevaju za sve antidijabetike kliničke pokuse o utjecaju na kardiovaskularne ishode i dokaze o sigurnosti. U procjeni učinka antidijabetika na kardiovaskularni rizik važna je gornja granična vrijednost dvostranog intervala pouzdanosti od 95 % (95 % CI) za procijenjeni omjer rizika. Svi antidijabetici s gornjom granicom omjera rizika ≥ 1,3 zahtijevaju dodatne sigurnosne provjere. Kardiovaskularna sigurnost oralnih antidijabetika posebno je važna u bolesnika sa zatajivanjem srca. S obzirom na veliki broj antidijabetika na tržištu, odluka o optimalnom liječenju DMT2 treba ovisiti o svim individualnim karakteristikama bolesnika i procijenjenom kardiovaskularnom riziku.SUMMARY: Croatia belongs to a group of European countries with a high cardiovascular risk and growing prevalence of diabetes mellitus type 2 (DMT2). According to data of the National Diabetes Registry (CroDiab registry), a total of 254,296 individuals aged >18 suffering from diabetes were registered in 2014 (7.9%). Along with hypertension and hyperlipidemia, DMT2 is one of the leading cardiovascular risk factors. Prompted by adverse cardiovascular effects of rosiglitazone, demonstrated in the RE-CORD study and subsequent meta-analyses, the main drug regulatory agencies require clinical trials of the effect on cardiovascular outcomes and safety evidence for all antidiabetic drugs. On assessing the effects of antidiabetic drugs on cardiovascular risk, the two-sided confidence interval upper borderline value of 95% (95% CI) is highly relevant for the estimated risk ratio. Additional safety testing is required for all antidiabetic drugs with the risk ratio upper limit ≥1.3. Cardiovascular safety of oral antidiabetic drugs is of special importance in patients with heart failure. Considering the great number of antidiabetic drugs on the market, decision on optimal DMT2 therapy should be made in dependence of specific characteristics of each individual patient and cardiovascular risk assessment.KLJUČNE RIJEČI: šećerna bolest, oralni antidijabetici, kardiovaskularne bolesti.KEYWORDS: diabetes mellitus, oral antidiabetic drugs, cardiovascular diseases. Pregledni rad Review article...

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Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus

Cited by 362 publications

References 269 publications

Metformin: safety in cardiac patients

Metformin: safety in cardiac patients

Recent important strategies in the management of chronic kidney disease

Cardiovascular Safety of Oral Antidiabetic Drugs.

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