BOX WARNING Lactic Acidosis:
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with RIOMET; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (> 5 mmol/L), decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio. When metformin is implicated as the cause of lactic acidosis, metformin plasma levels > 5 µg/mL are generally found.
The reported incidence of lactic acidosis in patients receiving metformin hydrochloride is very low (approximately 0.03 cases/1000 patient-years, with approximately 0.015 fatal cases/1000 patient-years). In more than 20,000 patient-years exposure to metformin in clinical trials, there were no reports of lactic acidosis. Reported cases have occurred primarily in diabetic patients with significant renal insufficiency, including both intrinsic renal disease and renal hypoperfusion, often in the setting of multiple concomitant medical/surgical problems and multiple concomitant medications. Patients with congestive heart failure requiring pharmacologic management, in particular those with unstable or acute congestive heart failure who are at risk of hypoperfusion and hypoxemia, are at increased risk of lactic acidosis. The risk of lactic acidosis increases with the degree of renal dysfunction and the patient’s age. The risk of lactic acidosis may, therefore, be significantly decreased by regular monitoring of renal function in patients taking RIOMET and by use of the minimum effective dose of RIOMET. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. RIOMET treatment should not be initiated in patients ≥80 years of age unless measurement of creatinine clearance demonstrates that renal function is not reduced, as these patients are more susceptible to developing lactic acidosis. In addition, RIOMET should be promptly withheld in the presence of any condition associated with hypoxemia, dehydration, or sepsis. Because impaired hepatic function may significantly limit the ability to clear lactate, RIOMET should generally be avoided in patients with clinical or laboratory evidence of hepatic disease. Patients should be cautioned against excessive alcohol intake, either acute or chronic, when taking RIOMET, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, RIOMET should be temporarily discontinued prior to any intravascular radiocontrast study and for any surgical procedure (see also PRECAUTIONS).
The onset of lactic acidosis often is subtle, and accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress. There may be associated hypothermia, hypotension, and resistant bradyarrhythmias with more marked acidosis. The patient and the patient’s physician must be aware of the possible importance of such symptoms and the patient should be instructed to notify the physician immediately if they occur (see also PRECAUTIONS). RIOMET should be withdrawn until the situation is clarified. Serum electrolytes, ketones, blood glucose and, if indicated, blood pH, lactate levels, and even blood metformin levels may be useful. Once a patient is stabilized on any dose level of RIOMET, gastrointestinal symptoms, which are common during initiation of therapy, are unlikely to be drug related. Later occurrence of gastrointestinal symptoms could be due to lactic acidosis or other serious disease.
Levels of fasting venous plasma lactate above the upper limit of normal but less than 5 mmol/L in patients taking RIOMET do not necessarily indicate impending lactic acidosis and may be explainable by other mechanisms, such as poorly controlled diabetes or obesity, vigorous physical activity, or technical problems in sample handling. (See also PRECAUTIONS.)
Lactic acidosis should be suspected in any diabetic patient with metabolic acidosis lacking evidence of ketoacidosis (ketonuria and ketonemia).
Lactic acidosis is a medical emergency that must be treated in a hospital setting. In a patient with lactic acidosis who is taking RIOMET, the drug should be discontinued immediately and general supportive measures promptly instituted. Because metformin hydrochloride is dialyzable (with a clearance of up to 170 mL/min under good hemodynamic conditions), prompt hemodialysis is recommended to correct the acidosis and remove the accumulated metformin. Such management often results in prompt reversal of symptoms and recovery. (See also CONTRAINDICATIONS and PRECAUTIONS.)
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NEWS HIGHLIGHTSMedia Articles Related to Riomet (Metformin)
Lasting Benefit Seen for Lifestyle Changes, Metformin in Diabetes (CME/CE)
Source: MedPage Today Endocrinology [2009.10.28]
Early use of lifestyle modifications or, to a lesser extent, metformin treatment, in people at risk for type 2 diabetes appeared to pay off for 10 years, researchers said.
Metformin May Lower Diabetics' Odds for Pancreatic Cancer
Source: MedicineNet metformin Specialty [2009.08.03]
Title: Metformin May Lower Diabetics' Odds for Pancreatic Cancer
Category: Health News
Created: 8/3/2009 7:00:00 AM
Last Editorial Review: 8/3/2009
Healthy Weight And Regular Physical Activity Could Prevent Diabetes For A Decade Says New Research
Source: Sports Medicine / Fitness News From Medical News Today [2009.11.01]
New research suggests that a period of careful eating and regular physical activity could prevent diabetes for up to a decade. US researchers followed up nearly 3,000 overweight people who had taken part in a three-year diabetes prevention programme. They had initially been divided into three groups, one undertaking a diet and exercise programme, the second taking metformin and the third a placebo. The report noted it was the dieters who reaped the most benefit.
Published Studies Related to Riomet (Metformin)
Efficacy and safety of pioglitazone/metformin fixed-dose combination therapy compared with pioglitazone and metformin monotherapy in treating patients with T2DM. [2009.10.14]
Abstract Background: Studies have shown that many patients with type 2 diabetes do not achieve optimal glycemic control, and progression of diabetes over time requires more than one pharmacotherapy to achieve glycemic goal. Objective: To examine the efficacy and safety of the fixed-dose combination (FDC) of pioglitazone 15 mg and metformin 850 mg versus its individual components in a twice-daily regimen over 24 weeks of treatment in type 2 diabetes patients who were currently not receiving antidiabetes therapy...
Metformin does not improve the reproductive or metabolic profile in women with polycystic ovary syndrome (PCOS). [2009.10]
To determine whether metformin, when given to women with polycystic ovary syndrome (PCOS), promotes folliculogenesis by prompting a drop in free sex steroids resulting in a compensatory follicle stimulating hormone (FSH) rise, we conducted a randomized, double-blind, placebo-controlled crossover clinical trial.
Comparison of vildagliptin and thiazolidinedione as add-on therapy in patients inadequately controlled with metformin: results of the GALIANT trial--a primary care, type 2 diabetes study. [2009.10]
AIM: To assess the efficacy and tolerability of vildagliptin compared with thiazolidinediones (TZDs) as an add on to metformin treatment in a primary care patient population with type 2 diabetes... CONCLUSIONS: This short-term study suggests that vildagliptin is as effective as TZDs after 3-month treatment as an add-on to metformin in a primary care population that included diverse patient subgroups.
Effect of adjunct metformin treatment on levels of plasma lipids in patients with type 1 diabetes. [2009.10]
BACKGROUND: In addition to its glucose-lowering effect, metformin treatment has been suggested to improve lipidaemia in patients with type 2 diabetes. In contrast, in patients with type 1 diabetes (T1DM), information about the effect of metformin treatment on lipidaemia is limited. In this study, we report the effect of a 1-year treatment with metformin vs. placebo on plasma lipids in T1DM patients and persistent poor glycaemic control... CONCLUSION: In patients with poorly controlled T1DM, at similar glycaemic levels, adjunct metformin therapy during 1 year significantly lowered levels of proatherogenic cholesterolaemia independent of statin therapy.
Twice-daily and three-times-daily dosing of a repaglinide/metformin fixed-dose combination tablet provide similar glycaemic control. [2009.10]
AIM: To assess the efficacy and safety of a new repaglinide/metformin fixed-dose combination (FDC) tablet administered either twice a day (BID) or three times a day (TID) for the management of type 2 diabetes... CONCLUSION: The efficacy of twice-daily dosing of a repaglinide/metformin FDC tablet was non-inferior to that of three-times-daily dosing.
Clinical Trials Related to Riomet (Metformin)
Study to Evaluate 24 Hour Blood Sugar Control in Subjects That Are Taking Saxagliptin 5 mg Added Onto Metformin XR 1500 XR mg Compared to Subjects Taking Metformin XR 1500 mg Uptitrated to Metformin XR 2000 mg [Recruiting]
Efficacy and Safety of Fixed Combination Therapy of Vildagliptin and Metformin (25/1000 mg Bid) in Patients With Type 2 Diabetes Inadequately Controlled With Prior Metformin Monotherapy (HbA1c 7.0-9.5%) [Recruiting]
The present study is designed to evaluate the efficacy and safety of fixed combination
therapy of vildagliptin and metformin (25/1000 mg bid) in patients with type 2 diabetes
inadequately controlled with prior metformin monotherapy.
Efficacy and Safety of Alogliptin Plus Metformin Compared to Glipizide Plus Metformin in Subjects With Type 2 Diabetes Mellitus [Recruiting]
The purpose of this study is to determine the safety and effectiveness of adding alogliptin
compared to glipizide with metformin in diabetic subjects.
Comparison of Repaglinide and Metformin Combination Tablet Versus Repaglinide and Metformin as Separate Tablets in Healthy Volunteers [Recruiting]
This trial is conducted in Asia. The aim of this clinical trial is to investigate the
bioequivalence of repaglinide and metformin combination tablet versus repaglinide and
metformin as coadministered tablets after meal.
The trial is designed as a three-period, six-sequence, single-dose, crossover
pharmacokinetic trial where the trial participant is randomised to one of six possible
treatment periods (Williams design). The trial participant will receive one single dose of
each trial product in varying order.
The Effect of Insulin Detemir in Combination With Liraglutide and Metformin Compared to Liraglutide and Metformin in Subjects With Type 2 Diabetes [Recruiting]
This trial is conducted in Europe and North America. The aim of this clinical trial is to
assess and compare the effect of insulin detemir in combination with liraglutide and
metformin versus liraglutide and metformin in people with type 2 diabetes.
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