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.)
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).
Media Articles Related to Metformin
Diabetes Drug Metformin Safe for Patients With Kidney Disease: Review
Source: MedicineNet metformin Specialty [2014.12.24]
Title: Diabetes Drug Metformin Safe for Patients With Kidney Disease: Review
Category: Health News
Created: 12/23/2014 12:00:00 AM
Last Editorial Review: 12/24/2014 12:00:00 AM
Published Studies Related to Metformin
Effect of combination therapy with repaglinide and metformin hydrochloride on
glycemic control in Japanese patients with type 2 diabetes mellitus. 
exercise... CONCLUSIONS: Combination therapy with repaglinide and metformin resulted in an
The effect of metformin on apoptosis in a breast cancer presurgical trial. 
presurgical trial... CONCLUSION: Overall, we found no significant modulation of apoptosis by
Efficacy and safety of canagliflozin versus glimepiride in patients with type 2
diabetes inadequately controlled with metformin (CANTATA-SU): 52 week results
from a randomised, double-blind, phase 3 non-inferiority trial. 
metformin... INTERPRETATION: Canagliflozin provides greater HbA1c reduction than does
Study design and rationale of a dose-ranging trial of LX4211, a dual inhibitor of
SGLT1 and SGLT2, in type 2 diabetes inadequately controlled on metformin
Sodium-glucose cotransporters 1 (SGLT1) and 2 (SGLT2) are the major cellular
transporters responsible for gastrointestinal (GI) glucose absorption and renal
glucose reabsorption, respectively... Safety is evaluated with particular focus on hypoglycemia, GI symptoms,
and incidence of genitourinary tract infections.
Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do
not have adequate glycemic control with metformin plus sulfonylurea: a 52-week
randomized trial. 
CONCLUSIONS: Findings suggest that canagliflozin may be a new therapeutic tool
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
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.
Reports of Suspected Metformin Side Effects
Renal Failure Acute (5),
Lactic Acidosis (3),
Suicide Attempt (3),
Intentional Overdose (2),
Completed Suicide (2),
Blood Creatinine Increased (2),
Diarrhoea (2), more >>
PATIENT REVIEWS / RATINGS / COMMENTS
Based on a total of 20 ratings/reviews, Metformin has an overall score of 8.05. The effectiveness score is 8.20 and the side effect score is 8.20. 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
|Overall rating:|| || |
|Effectiveness:|| || Highly Effective|
|Side effects:|| || Severe Side Effects|
|Condition / reason:|| || pcos|
|Dosage & duration:|| || 2000mg/day taken twice a day for the period of 4 months|
|Other conditions:|| || none|
|Other drugs taken:|| || none|
|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.|
Metformin review by 41 year old male patient
|Overall rating:|| || |
|Effectiveness:|| || Considerably Effective|
|Side effects:|| || Mild Side Effects|
|Condition / reason:|| || none|
|Dosage & duration:|| || 2 g a day (dosage frequency: twice) for the period of 1 year|
|Other conditions:|| || none|
|Other drugs taken:|| || alpha-lipoic acid|
|Benefits:|| || Well... what can I say? During the treatment I mentioned a considerable pressure decrease, and for sure it was a notable blood sugar decrease. I would recommend this drug to evedybody with sugar diabetes type II.
Adherence to a diabetic diet is an important aspect of controlling elevated blood sugar in patients with diabetes. The American Diabetes Association (ADA) has provided guidelines for a diabetic diet. The ADA diet is a balanced, nutritious diet that is low in fat, cholesterol, and simple sugars. The total daily calories are evenly divided into three meals. In the past two years, the ADA has lifted the absolute ban on simple sugars. Small amounts of simple sugars are allowed when consumed with a complex meal. For more, please read the Diabetic Diet article.
|Side effects:|| || none|
|Comments:|| || as prescribed|
Metformin review by 50 year old male patient
|Overall rating:|| || |
|Effectiveness:|| || Marginally Effective|
|Side effects:|| || No Side Effects|
|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|
|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.|
Page last updated: 2014-12-24