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Metformin Kidney Injury

Metabolic Effects Of Metformin In Patients With Acute Renal Failure

Metabolic Effects Of Metformin In Patients With Acute Renal Failure

Metformin use has been associated with significant disturbances in acid-base balance. Metformin remains the first-line therapy for majority of patients with type 2 diabetes mellitus. Its metabolic effects have provided great support for its use in diabetes management. However, risks of renal impairment and lactic acidosis have always warranted close monitoring in patients with predisposing factors to these events. In fact, lactic acidosis has been associated with renal impairment. Metformin is not metabolized in the liver and is excreted by active tubular secretion. The risk of developing lactic acidosis greatly depends on the magnitude of each patient’s renal impairment and their age. Nonetheless, these studies fail to take into consideration those patients with renal failure. The majority of trials out there exclude patients with renal defects due to its nephrotoxic potential. The nephrotoxicity of increased levels of metformin relies on its effect on renal mitochondrial activity. Previous studies have demonstrated that therapeutic doses of metformin are not associated with risk of lactic acidosis. Renal mitochondrial dysfunction can lead to tubular cell ischemia and increased lactic acid production. Hence, those patients with renal impairment will warrant closer monitoring and dose optimization strategies to prevent these complications while obtaining optimal glucose control. Recently, renal dose adjustments changed. Now patients are to be monitored based on glomerular filtration rate and not serum creatinine for metformin therapy. A recent study conducted by David Cucchiari and colleagues evaluated the dose-related effects of metformin on acid-base balance in patients with diabetes who develop acute renal failure. In this cross-sectional study, 126 patients were i Continue reading >>

Acute Kidney Injury, Plasma Lactate Concentrations And Lactic Acidosis In Metformin Users: A Godarts Study.

Acute Kidney Injury, Plasma Lactate Concentrations And Lactic Acidosis In Metformin Users: A Godarts Study.

Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: A GoDarts study. by Logan Thomison | Apr 23, 2017 | 0 comments Connelly PJ, Lonergan M, Soto-Pedre E, Donnelly L, Zhou K, Pearson ER, Connelly PJ, Lonergan M, Soto-Pedre E, Donnelly L, Zhou K, Pearson ER, (click to view) Connelly PJ, Lonergan M, Soto-Pedre E, Donnelly L, Zhou K, Pearson ER, Diabetes, obesity & metabolism 2017 04 21() doi 10.1111/dom.12978 Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. We undertook a population-based case-control study of lactic acidosis in 1,746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994-2014. AKI was stratified by severity according to Kidney Disease: Improving Global Outcomes guidelines. Mixed effects logistic and linear regression was used to analyse lactic acidosis risk and lactate concentrations respectively. 82 cases of lactic acidosis were identified. In Type 2 diabetes, those treated with metformin had a greater incidence of lactic acidosis (45.7 per 100,000 patient years; 95% CI 35.9-58.3) compared to those not exposed to this drug (11.8 per 100,000 patient years; 95% CI 4.9-28.5). Lactate concentrations were 0.34 mmol/L higher in the metformin-exposed cohort (p < 0.001). The risk of lactic acidosis was higher in metformin users (OR 2.3; p = 0.002) and increased with AKI severity (stage 1: OR 3.0, p = 0.002; stage Continue reading >>

Case Studies : Health Informatics Centre : University Of Dundee

Case Studies : Health Informatics Centre : University Of Dundee

Health Informatics Centre / HIC Services / HIC Case Studies / Case studies Acute kidney injury, metformin & lactic acidosis Metformin is the most prescribed drug used in the treatment of type 2 diabetes and is one of the top 10 drugs prescribed in the world. This drug has an excellent safety record, however, there remains debate about its association with the potentially fatal condition lactic acidosis. As metformin is excreted by the kidneys it has been widely accepted that this drug should be stopped during illnesses that may increase the risk of acute kidney injury (AKI). For example, the current NHS England Think Kidneys initiative recommends this. However, there has been no systematic population based study of this association and the only evidence of this relationship is based upon limited case reports and retrospective case series. This aim of this study was to comprehensively investigate the association between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. A population-based case-control study of lactic acidosis in 1,746 participants with type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994-2014 was undertaken. This utilised the Genetics of Diabetes Audit and Research Tayside (GoDARTs) cohort. This is a Health Informatics Centre (HIC) managed cohort that links clinical records by a patient-specific identifier, the Community Health Index (CHI) number, allowing the creation and maintenance of a sophisticated regional health informatics resource of approximately 18,000 cases and controls. Due to this unique resource provided by HIC we obtained over 10 years of follow up of people in this cohort with and without diabetes and captured allbiochemistry test Continue reading >>

A Case Of Metformin-induced Acute Kidney Injury Without Lactic Acidosis: A Case Report

A Case Of Metformin-induced Acute Kidney Injury Without Lactic Acidosis: A Case Report

A Case of Metformin-Induced Acute Kidney Injury without Lactic Acidosis: A Case Report *** A Case of Metformin-Induced Acute Kidney Injury without Lactic Acidosis: A Case Report 1Department of Internal Medicine, Hanyang University College of Medicine, Seoul, Korea. [email protected] 2Department of Internal Medicine, Hanyang University College of Medicine, Guri, Korea. Metformin is an oral antidiabetic drug in the biguanide class, which is used for type 2 diabetes. The side effects of metformin are mostly limited to digestive tract symptoms, such as diarrhea, flatulence and abdominal discomfort. The most serious potential adverse effect of metformin is lactic acidosis. A 51-year-old man was admitted due to hypoglycemia as a result of an overdose of antidiabetic drugs. He took massive dose of metformin. Conservative treatment failed for metabolic acidosis without lactic acidosis accompanied by acute kidney injury. Hemodialysis was executed to correct the high anion gap metabolic acidosis and acute kidney injury, and the patient recovered fully from metabolic acidosis. This case illustrates that the presence of clinical conditions, such as metformin-induced acute kidney injury and metabolic acidosis, can be developed without lactic acidosis. Prompt recognition of metabolic acidosis and early intervention with hemodialysis can result in a successful clinical outcome. Continue reading >>

Clarifying The Relationship Between Metformin, Acute Kidney Injury And Lactic Acidosis

Clarifying The Relationship Between Metformin, Acute Kidney Injury And Lactic Acidosis

Clarifying the relationship between metformin, acute kidney injury and lactic acidosis We read, with interest, the News & Views article by C. Rhee and K. Kalantar-Zadeh (Diabetes mellitus: Complex interplay between metformin, AKI and lactic acidosis. Nat. Rev. Nephrol. 13, 521522 (2017) ) 1 , which discusses our recent work looking at the relationship between metformin, acute kidney injury (AKI) and lactic acidosis 2 , 3 . In response to this discussion of some of our findings, we would like to highlight several points. First, Connelly et al. demonstrated that 80% of lactic acidosis within the study cohort occurred in the presence of AKI 3 . In view of the effectiveness of treatment and increasing evidence of the beneficial cardiovascular effects of metformin, we feel that metformin should be only temporarily discontinued in patients with a condition that predisposes them to acute AKI; this advice is similar to the advice given for angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers. Second, although we acknowledge the difficulties of accurately identifying metformin-associated lactic acidosis (MALA) cases in observational studies, we do not agree that the crude incidence rate of lactic acidosis observed in the study by Connelly et al. is biased because it differs from rates reported by others. Instead, we would like to emphasize that crude incidence rates disregard the structure of the population. Thus, comparing crude incidence rates alone can be misleading before standardization is carried out to remove the effect of differential structures in populations under comparison. Third, it was also suggested that the absence of a 'new-user' design in the study by Bell et al. 2 may not have accounted for patients who stopped using metformin or d Continue reading >>

Diabetic Ckd Patients Survive Longer With Metformin

Diabetic Ckd Patients Survive Longer With Metformin

Diabetic CKD Patients Survive Longer With Metformin Diabetic CKD Patients Survive Longer With Metformin Initiation of metformin rather than a sulfonylurea as treatment for type 2 diabetes among patients with chronic kidney disease (CKD) is associated with decreased mortality risk, a study found. Patients with moderately to severely reduced estimated glomerular filtration rate (eGFR) experience the largest absolute risk reduction, according to researchers. A team led by James S. Floyd, MD, of the University of Washington in Seattle, studied a cohort of 175,296 veterans who received care from the Veterans Health Administration for at least 1 year before initiating monotherapy for type 2 diabetes with either metformin or a sulfonylurea from 2004 to 2009. Of these patients, 5121 died. Compared with patients starting on a sulfonylurea, those starting on metformin had a 36% decreased risk of death, with the magnitude of risk reduction varying by eGFR, Dr Floyd and colleagues reported online ahead of print in the Journal of General Internal Medicine. Among patients with an eGFR of 90 mL/min/1.73 m2 or higher, those who started on metformin had a statistically significant 41% decreased risk of death compared with those who started on a sulfonylurea. Among patients with an eGFR of 4559 mL/min1.73 m2, the metformin group had a statistically significant 20% decreased risk of death versus the sulfonylurea group. The investigators observed the greatest risk difference among patients with an eGFR of 3044 mL/min/1.73 m2. In this group, patients started on metformin had 12.1 fewer deaths per 1000 person-years compared with those started on a sulfonylurea. Among patients with eGFR values of 90 mL/min/1.73 m2 or higher and 6089 and 4559 mL/min/1.73 m2, those started on metformin experie Continue reading >>

Metformin And Contrast-induced Acute Kidney Injury In Diabetic Patients Treated With Primary Percutaneous Coronary Intervention For St Segment Elevation Myocardial Infarction: Amulticenter Study

Metformin And Contrast-induced Acute Kidney Injury In Diabetic Patients Treated With Primary Percutaneous Coronary Intervention For St Segment Elevation Myocardial Infarction: Amulticenter Study

Volume 220 , 1 October 2016, Pages 137-142 Metformin and contrast-induced acute kidney injury in diabetic patients treated with primary percutaneous coronary intervention for ST segment elevation myocardial infarction: Amulticenter study Author links open overlay panel MarianneZellera To analyze the association between chronic metformin treatment and the development of contrast-induced acute kidney injury (CI-AKI) after primary percutaneous coronary intervention (PCI) for ST segment elevation myocardial infarction (STEMI). Patients with type 2 diabetes mellitus (T2DM) treated with PCI <24h in 2 coronary care units were included. Serum creatinine (Cr) was measured before and <48h after PCI. CI-AKI was defined as an increase in Cr>27mol/l (0.3mg/dl) or >50% over baseline after PCI. Since PCI was urgent, metformin could not be withheld prior to PCI but was usually stopped after PCI. Among the 372 patients included, 147 (40%) were using metformin, which had older diabetes, but had risk factors similar to patients without metformin. Baseline eGFR was better in patients under metformin therapy. After PCI, we observed an increase of 10% in Cr, for both groups. There was a trend toward a lower rate of CI-AKI in patients under metformin (16% vs 25%, p=0.051). In patients with chronic kidney disease, 31 (26%) were under metformin therapy, and the rate of CI-AKI was similar in both groups (41% vs 40%, p=0.915). By multivariate analysis, metformin showed a trend toward a reduced rate of CI-AKI, even when adjusted for confounding (OR (95% CI): 0.548 (0.2761.087)). No case of lactic acidosis was reported during the hospital stay. Moreover, there was no increased rate of cardiogenic shock or death with metformin treatment. In this multicenter observational study, chronic metformin tr Continue reading >>

Contrast Induced Acute Kidney Injury (aki) - General Practice Notebook

Contrast Induced Acute Kidney Injury (aki) - General Practice Notebook

contrast induced acute kidney injury (AKI) contrast induced nephropathy (CIN) is the third leading cause of hospital acquired renal failure and is associated with significant morbidity and mortality (1) chronic kidney disease is the primary predisposing factor for CIN (estimated glomerular filtration rate<60 ml/1.73 m2 represents significant renal dysfunction and defines patients at high risk) nephropathy induced by contrast medium is defined as an impairment in renal function that occurs within 72 hours of giving contrast medium (2) characterised by an increase in serum creatinine of at least 44 mol/litre (or 25% above the baseline) the peak in creatinine level is typically three to five days after administration of contrast medium - the creatinine level returns to baseline values within two weeks CIN accounts for about 12% of all cases of hospital acquired renal failure concurrent use of nephrotoxic drugs (non-steroidal anti-inflammatory drugs, biguanides, aminoglycosides) modifiable risk factors for CIN include hydration status, the type and amount of contrast, use of concomitant nephrotoxic agents and recent contrast administration cornerstone of CIN prevention, in both the high and low risk patients, is adequate parenteral volume repletion in patients at increased risk for CIN the use of low or iso-osomolar contrast agents should be utilized and strategies employed to minimize contrast volume. In these patients serum creatinine should be obtained forty-eight hours post procedure and it is often appropriate to continue withholding medications such as metformin or non steroidal anti-inflammatories until renal function returns to normal acute renal failure is a well known complication of procedures that involve iodinated contrast media in diabetic patients type 2 dia Continue reading >>

Metformin And Acute Kidney Injury: Is It The Culprit?

Metformin And Acute Kidney Injury: Is It The Culprit?

Endocrine Abstracts (2014) 34 P251 | DOI: 10.1530/endoabs.34.P251 Metformin and acute kidney injury: is it the culprit? Blackpool Victoria Hospital, Blackpool, UK. Three people (two males), with mean age (range) 65 (4975) years, presented as emergencies with acute renal failure (AKI). They had type 2 diabetes mellitus, with mean duration 7 (212) years. All three were taking anti-hypertensive therapy: two were on ramipril and one on losartan and indapamide. All three were taking metformin with mean daily dose 2.6 (1.73.0) g. All three patients had mild renal impairment (CKD stage 3), but renal function was stable 23 months before presentation with mean blood urea 8.1 (5.69.5) mmol/l, creatinine 118 (108133) mol/l and eGFR 49 (4359) ml/min per l. They presented with a 1 week history of symptoms including vomiting (2), diarrhoea (2), unsteadiness (3), confusion (1), and falls (2). On admission the mean blood glucose was 8.5 (4.913.0) mmol/l, urea 32 (22 42) mmol/l, and creatinine 763 (652978)mol/l. They were acidotic with mean pH 7.19 (7.157.23), bicarbonate 15.6 (10.321.2) mmol/l, and lactate 3.6 (2.05.9) mmol/l. The mean blood metformin level was raised at 12.2 (11.014.3) mg/l. The accepted therapeutic range is 0.52.0 mg/l). Metformin, ramipril, losartan and indapamide were discontinued. One patient required haemofiltration but in all three urine output soon improved with i.v. fluid therapy. Renal function was back to baseline 23 months later with mean blood urea 7.5 (6.88.4) mmol/l, creatinine 113 (104131) mol/l and eGFR 52 (4560) ml/min per l. Metformin is eliminated, unchanged, by renal excretion. We suggest that inappropriately high metfomin doses in these patients with mild renal impairment has led to escalating blood metformin levels, which in turn largely account Continue reading >>

Acute Kidney Injury: A Guide To Diagnosis And Management

Acute Kidney Injury: A Guide To Diagnosis And Management

Acute kidney injury is characterized by abrupt deterioration in kidney function, manifested by an increase in serum creatinine level with or without reduced urine output. The spectrum of injury ranges from mild to advanced, sometimes requiring renal replacement therapy. The diagnostic evaluation can be used to classify acute kidney injury as prerenal, intrinsic renal, or postrenal. The initial workup includes a patient history to identify the use of nephrotoxic medications or systemic illnesses that might cause poor renal perfusion or directly impair renal function. Physical examination should assess intravascular volume status and identify skin rashes indicative of systemic illness. The initial laboratory evaluation should include measurement of serum creatinine level, complete blood count, urinalysis, and fractional excretion of sodium. Ultrasonography of the kidneys should be performed in most patients, particularly in older men, to rule out obstruction. Management of acute kidney injury involves fluid resuscitation, avoidance of nephrotoxic medications and contrast media exposure, and correction of electrolyte imbalances. Renal replacement therapy (dialysis) is indicated for refractory hyperkalemia; volume overload; intractable acidosis; uremic encephalopathy, pericarditis, or pleuritis; and removal of certain toxins. Recognition of risk factors (e.g., older age, sepsis, hypovolemia/shock, cardiac surgery, infusion of contrast agents, diabetes mellitus, preexisting chronic kidney disease, cardiac failure, liver failure) is important. Team-based approaches for prevention, early diagnosis, and aggressive management are critical for improving outcomes. The incidence of acute kidney injury has increased in recent years, both in the community and in hospital settings.1,2 Continue reading >>

Metformin Intoxication With Severe Lactic Acidosis And Acute Kidney Injury Treated With Sustained Low-efficiency Dialysis (sled)

Metformin Intoxication With Severe Lactic Acidosis And Acute Kidney Injury Treated With Sustained Low-efficiency Dialysis (sled)

Metformin intoxication with severe lactic acidosis and Acute Kidney Injury treated with sustained low-efficiency dialysis (SLED) We report here on a case of MALA due to metformin accumulation in a diabetic patient with AKI on CKD, focusing on relevant pharmacokinetic issues that should guide the choice of the most appropriate modality of emergency renal replacement therapy (RRT). A 76-year-old man with type 2 diabetes, CKD (usual serum creatinine [sCr] concentration 1.8 mg/dL, eGFR 36 mL/min/1.73 m2) and ischemic cardiomyopathy presented with a 48-hour history of vomiting, abdominal pain, hypotension and oliguria after uncomplicated day-surgery for inguinal hernia three days earlier. His usual medications included aspirin 100 mg, ramipril 7.5 mg, bisoprolol 2.5 mg, furosemide 25 mg bid, metformin 1000 mg tid, glimepiride 1 mg. Physical examination revealed an oliguric 72 Kg man in moderate respiratory distress, with cold extremities and a large hematoma of the abdominal wall (7 x 6 cm on CT scan, extending to the scrotum and left thigh). Blood pressure was 90/50 mmHg while on dopamine 8 mg/Kg/min, pulse rate 56 beats/min, respirations 32 breaths/min, peripheral oxygen saturation 98% on 50% O2, tympanic temperature 35.5 C. Initial laboratory workup showed a severe anion gap (AG) metabolic acidosis with hyperlactatemia and AKI on CKD (Fig.1). Other routine serum values and urine toxicology tests were unremarkable. RRT was started with an AK 200ultra machine (Gambro/Baxter, Mirandola, Italy) and a 1.8 m2 polysulfone F8 HPS filter (Fresenius, Palazzo Pignano, Italy). A 16-hour sustained low-efficiency dialysis (SLED) session with regional citrate anticoagulationwas planned (blood flow rate 200 mL/min, bicarbonate [32 mmol/L] dialysis fluid rate 300 mL/min, countercurrent f Continue reading >>

Metformin-associated Lactic Acidosis Following Acute Kidney Injury. Efficacious Treatment With Continuous Renal Replacement Therapy.

Metformin-associated Lactic Acidosis Following Acute Kidney Injury. Efficacious Treatment With Continuous Renal Replacement Therapy.

A comment on this article appears in " Type 2 diabetes, metformin and lactic acidosis-defining the risk and promoting safe practice. " Diabet Med. 2012 Feb;29(2):161-3. INTRODUCTION: Metformin is a biguanide anti-hyperglycaemic drug. Metformin-associated lactic acidosis may sometimes be life-threatening. Continuous renal replacement therapy has been suggested as a method for resolving this extremely dangerous metabolic state. We describe the history of six patients admitted to the intensive care unit over a 28-month period in pre-shock conditions because of severe lactic acidosis, attributed to metformin-associated lactic acidosis, and successfully treated. METHODS: We reviewed the charts of six patients admitted to our intensive care unit between January 2008 and May 2010. After initial assessment, all patients were treated with continuous renal replacement therapy. Admission serum lactate and creatinine levels, pH, need for ventilatory and cardiovascular support, as well as continuous renal replacement therapy details and length of stay were reviewed. RESULTS: Admission pH levels of the six patients ranged between pH 6.63 and 7.0 and their serum lactate levels ranged between 12 and 27 mmol/l; the estimated creatinine clearance ranged between 6 and 24 ml min(-1) 1.73 m(-2) . All patients required vasoactive support and five required ventilatory support. Lactate levels decreased to near zero with continuous renal replacement therapy within 7-19 h in five of the patients whose intensive care unit length of stay ranged between 1 and 5 days. One patient's length of stay reached 11 days because of pneumonia, one died from multi-organ failure and another suffered permanent neurological damage following prolonged cardiopulmonary resuscitation before continuous renal replacem Continue reading >>

Metformin-associated Acute Kidney Injury And Lactic Acidosis

Metformin-associated Acute Kidney Injury And Lactic Acidosis

Copyright © 2011 David Arroyo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Objectives. Metformin is the preferred oral antidiabetic agent for type 2 diabetes. Lactic acidosis is described as a rare complication, usually during an acute kidney injury (AKI). Material and Methods. We conducted a prospective observational study of metformin-associated AKI cases during four years. 29 cases were identified. Previous renal function, clinical data, and outcomes were recorded. Results. An episode of acute gastroenteritis precipitated the event in 26 cases. Three developed a septic shock. Three patients died, the only related factor being liver dysfunction. More severe metabolic acidosis hyperkalemia and anemia were associated with higher probabilities of RRT requirement. We could not find any relationship between previous renal dysfunction and the outcome of the AKI. Conclusions. AKI associated to an episode of volume depletion due to gastrointestinal losses is a serious complication in type 2 diabetic patients on metformin. Previous renal dysfunction (mild-to-moderate CKD) has no influence on the severity or outcome. 1. Introduction Metformin is the only biguanide extensively used these days, and has become the first-line oral drug in type 2 diabetes [1]. Metformin-associated lactic acidosis has not been thoroughly characterized. Meta-analyses and large studies have been unable to establish an epidemiological association, probably due to its low incidence rate. However, most cases have been reported associated with an episode of acute kidney injury (AKI), predominantly in intensive care units [ Continue reading >>

Acute Kidney Injury, Plasma Lactate Concentrations And Lactic Acidosis In Metformin Users: A Godarts Study.

Acute Kidney Injury, Plasma Lactate Concentrations And Lactic Acidosis In Metformin Users: A Godarts Study.

Diabetes Obes Metab. 2017 Nov;19(11):1579-1586. doi: 10.1111/dom.12978. Epub 2017 Jul 5. Acute kidney injury, plasma lactate concentrations and lactic acidosis in metformin users: A GoDarts study. Division of Molecular and Clinical Medicine, School of Medicine, University of Dundee, Dundee, UK. Metformin is renally excreted and has been associated with the development of lactic acidosis. Although current advice is to omit metformin during illnesses that may increase the risk of acute kidney injury (AKI), the evidence supporting this is lacking. We investigated the relationship between AKI, lactate concentrations and the risk of lactic acidosis in those exposed to metformin. We undertook a population-based case-control study of lactic acidosis in 1746 participants with Type 2 diabetes and 846 individuals without diabetes with clinically measured lactates with and without AKI between 1994 and 2014. AKI was stratified by severity according to "Kidney Disease: Improving Global Outcomes" guidelines. Mixed-effects logistic and linear regression were used to analyse lactic acidosis risk and lactate concentrations, respectively. Eighty-two cases of lactic acidosis were identified. In Type 2 diabetes, those treated with metformin had a greater incidence of lactic acidosis [45.7 per 100 000 patient years; 95% confidence interval (CI) 35.9-58.3] compared to those not exposed to this drug (11.8 per 100 000 patient years; 95% CI 4.9-28.5). Lactate concentrations were 0.34 mmol/L higher in the metformin-exposed cohort (P < .001). The risk of lactic acidosis was higher in metformin users [odds ratio (OR) 2.3; P = .002] and increased with AKI severity (stage 1: OR 3.0, P = .002; stage 2: OR 9.4, P < .001; stage 3: OR 16.1, P < .001). A clear association was found between metformin, la Continue reading >>

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

Use Of Metformin In The Setting Of Mild-to-moderate Renal Insufficiency

ADVANTAGES OF METFORMIN There is some evidence that early treatment with metformin is associated with reduced cardiovascular morbidity and total mortality in newly diagnosed type 2 diabetic patients (4). However, the data come from a small subgroup of a much larger trial. In contrast, despite multiple trials of intensive glucose control using a variety of glucose-lowering strategies, there is a paucity of data to support specific advantages with other agents on cardiovascular outcomes (5–7). In the original UK Prospective Diabetes Study (UKPDS), 342 overweight patients with newly diagnosed diabetes were randomly assigned to metformin therapy (8). After a median period of 10 years, this subgroup experienced a 39% (P = 0.010) risk reduction for myocardial infarction and a 36% reduction for total mortality (P = 0.011) compared with conventional diet treatment. Similar benefits were not observed in those randomly assigned to sulfonylurea or insulin. In an 8.5-year posttrial monitoring study, after participants no longer were randomly assigned to their treatments, individuals originally assigned to metformin (n = 279) continued to demonstrate a reduced risk for both myocardial infarction (relative risk 33%, P = 0.005) and total mortality (relative risk 27%, P = 0.002) (9). The latter results are even more impressive when one considers that HbA1c levels in all initially randomly assigned groups had converged within 1 year of follow-up. Unlike sulfonylureas, thiazolidinediones, and insulin, metformin is weight neutral (10), which makes it an attractive choice for obese patients. Furthermore, the management of type 2 diabetes can be complicated by hypoglycemia, which can seriously limit the pursuit of glycemic control. Here, too, metformin has advantages over insulin and some Continue reading >>

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