BOX WARNING
Lactic Acidosis
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin; 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 mcg/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 metformin and by use of the minimum effective dose of metformin. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin 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, metformin 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, metformin 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 metformin hydrochloride tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin 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). Metformin hydrochloride tablets 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 metformin, 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 metformin 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 metformin, 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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METFORMIN SUMMARY
Metformin hydrochloride is an oral antihyperglycemic drug used in the management of type 2 diabetes.
Metformin hydrochloride tablets, as monotherapy, are indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. Metformin is indicated in patients 10 years of age and older.
Metformin may be used concomitantly with a sulfonylurea or insulin to improve glycemic control in adults (17 years of age and older).
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NEWS HIGHLIGHTSMedia Articles Related to 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 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 Metformin
Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance [Active, not recruiting]
The primary objective of this randomized, parallel group, double-blind, placebo-controlled
study is to determine whether treatment with metformin enhances insulin sensitivity in a
group of ethnically diverse obese insulin-resistant adolescents with normal glucose
tolerance.
Drug Interaction With Metformin [Completed]
The purpose of the study is to determine the effect of metformin on dapagliflozin exposure
and the effect of dapagliflozin on metformin exposure in healthy volunteers. Additionally,
the safety and tolerability of dapagliflozin will be assessed in the presence and absence of
metformin in healthy volunteers
Rosiglitazone-Metformin Combination Versus Metformin-Sulfonylurea Combination On Beta-Cell Function In Type 2 Diabetes [Active, not recruiting]
It has been shown in previous study that progressive glycemic deterioration was associated
with progressive loss of b-cell function, measured by the decrease in plasma insulin levels,
irrespective of the therapy used (diet, sulfonylureas or metformin).There is growing evidence
that thiazolidinediones could have a positive action on the b-cell function. But it has not
yet been demonstrated that they could protect from a deterioration in insulin secretion in
the long term. So, it appears interesting to study the long term evolution of the b-cell
function and the possible protection with rosiglitazone in patients with type 2 diabetes
showing evidence of loss of b-cell function with metformin alone.
Efficacy and Safety of Prandial Inhalation of Technosphere/Insulin in Combination With Metformin or Technosphere/Insulin Alone Versus 2 Oral Anti-Diabetic Agents in Subjects With Type 2 Diabetes [Active, not recruiting]
to demonstrate the efficacy of inhaled Technosphere/Insulin in combination with metformin
versus combination metformin and a secretagogue
To Compare the Effect of Liraglutide When Given Together With Metformin With the Effect of Metformin Given Alone and With the Effect of Glimepiride and Metformin Given Together [Active, not recruiting]
This trial is conducted in Europe, Oceania, Africa, Asia and South America.
This trial is designed to show the effect of treatment with liraglutide when adding to
existing metformin therapy and to compare it with the effects of metformin monotherapy and
combination therapy of metformin and glimepiride.
The 26 weeks double-blind period will be followed by an 18 months open label extension.
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PATIENT REVIEWS / RATINGS / COMMENTSBased on a total of 13 ratings/reviews, Metformin has an overall score of 7.77. The effectiveness score is 8 and the side effect score is 8. The scores are on ten point scale: 10 - best, 1 - worst. Below are selected reviews: the highest, the median and the lowest rated.
| | Metformin review by 30 year old female patient | | | Rating |
| Overall rating: | |  |
| Effectiveness: | | Highly Effective |
| Side effects: | | Severe Side Effects | | |
Treatment Info |
| Condition / reason: | | pcos |
| Dosage & duration: | | 2000mg/day taken twice a day for the period of 4 months |
| Other conditions: | | none |
| Other drugs taken: | | none | | |
Reported Results |
| Benefits: | | As for Polycystic Ovary Syndrome patient, the main goal of the treatment was to regulate ovulation, and to regulate menstrual period. After 4 months of treatment (only 2 months therapeutic dose), I become pregnant and now have a beautiful son. |
| Side effects: | | Persistant nausea, diarrhea after every single dose. |
| Comments: | | Treatment started as a very low dose at 500mg/day at the evening meal. Dose was increased by 500mg on the second week and stayed the same for 3 weeks. On week 5 dose was increased by 500mg for another 2 weeks. Another 500mg increase up to 2000mg/day until beginning of the pregnancy. |
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| | Metformin review by 57 year old female patient | | | Rating |
| Overall rating: | |  |
| Effectiveness: | | Considerably Effective |
| Side effects: | | Moderate Side Effects | | |
Treatment Info |
| Condition / reason: | | diabetes |
| Dosage & duration: | | 2 pills, taken twice for the period of continuing |
| Other conditions: | | high blood pressure |
| Other drugs taken: | | glyburide | | |
Reported Results |
| Benefits: | | Apparantly this drug helps to use the sugars be of use to the body, so my sugar levels went down. |
| Side effects: | | I had gastrointestinal upset, including diarrhea, cramps, and nausea. Since I took a combination of drugs when beginning treatment, I am not sure which one caused a weight gain. It is extremely difficult for me to shift a pound although I am absolutely stringent about my diet. |
| Comments: | | took the pills as prescribed, worked through the nausea and got on with it. |
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| | Metformin review by 50 year old male patient | | | Rating |
| Overall rating: | | |
| Effectiveness: | | Marginally Effective |
| Side effects: | | No Side Effects | | |
Treatment Info |
| Condition / reason: | | diabetes |
| Dosage & duration: | | max allowed (dosage frequency: daily) for the period of 120 days |
| Other conditions: | | high blood pressure; depression; sleep apnea |
| Other drugs taken: | | aspirin, Lasix | | |
Reported Results |
| Benefits: | | There was no perceptible benefit to the patient from his point of view; there was an apparent improvement as measured by the doctor. The doctor advised continuation of the treatment. |
| Side effects: | | There was no perceptible side effect experienced by the patient; this is possibly possibly due to the inattentive nature of the patients deep depression. The patient also had extreme sleep apnea. |
| Comments: | | Started the treatment for 60 days at maximum recommended rate; the patient found no perceptible improvement he then trailed off to stop treatment over the following 60 days. |
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Page last updated: 2009-11-01
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