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Glucophage (Metformin Hydrochloride) - Summary



Lactic Acidosis:

Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with GLUCOPHAGE or GLUCOPHAGE XR; 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 GLUCOPHAGE or GLUCOPHAGE XR and by use of the minimum effective dose of GLUCOPHAGE or GLUCOPHAGE XR. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. GLUCOPHAGE or GLUCOPHAGE XR 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, GLUCOPHAGE and GLUCOPHAGE XR 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, GLUCOPHAGE and GLUCOPHAGE XR 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 GLUCOPHAGE or GLUCOPHAGE XR, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, GLUCOPHAGE and GLUCOPHAGE XR 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). GLUCOPHAGE and GLUCOPHAGE XR 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 GLUCOPHAGE or GLUCOPHAGE XR, 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 GLUCOPHAGE or GLUCOPHAGE XR 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 GLUCOPHAGE or GLUCOPHAGE XR, 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.)



GLUCOPHAGE® (metformin hydrochloride) Tablets and GLUCOPHAGE® XR (metformin hydrochloride) Extended-Release Tablets are oral antihyperglycemic drugs used in the management of type 2 diabetes.

GLUCOPHAGE (metformin hydrochloride) Tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults and children with type 2 diabetes mellitus.

GLUCOPHAGE XR (metformin hydrochloride) Extended-Release Tablets is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

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Published Studies Related to Glucophage (Metformin)

Anagliptin and sitagliptin as add-ons to metformin for patients with type 2 diabetes: a 24-week, multicentre, randomized, double-blind, active-controlled, phase III clinical trial with a 28-week extension. [2015]
We conducted a 24-week, multicentre, double-blind, randomized study with a 28-week extension to compare the efficacy and safety of anagliptin and sitagliptin as an add-on to metformin in patients with type 2 diabetes. Patients inadequately controlled on metformin were randomized to either anagliptin (100 mg twice daily, n = 92) or sitagliptin (100 mg once daily, n = 88)...

Effect of combination therapy with repaglinide and metformin hydrochloride on glycemic control in Japanese patients with type 2 diabetes mellitus. [2014]
exercise... CONCLUSIONS: Combination therapy with repaglinide and metformin resulted in an

Lipid profiling reveals different therapeutic effects of metformin and glipizide in patients with type 2 diabetes and coronary artery disease. [2014]
CONCLUSIONS: Our findings revealed the differential therapeutic effects of

Metformin for non-diabetic patients with coronary heart disease (the CAMERA study): a randomised controlled trial. [2014]
diabetes... INTERPRETATION: Metformin had no effect on cIMT and little or no effect on

The effect of metformin on apoptosis in a breast cancer presurgical trial. [2013]
presurgical trial... CONCLUSION: Overall, we found no significant modulation of apoptosis by

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Clinical Trials Related to Glucophage (Metformin)

Evaluate Adherence to Treatment With Glucophage Sachets Versus Tablets in Diabetes Type 2 Patients Previously Treated With Metformin Tablets [Withdrawn]
This is an open-label, multicenter, two-arm, parallel, randomized phase 4 study to compare the compliance in diabetes type 2 patients treated with Glucophage sachets versus patients treated with Glucophage tablets.

Bioequivalence Study of 2.5-mg Saxagliptin and 500-mg Glucophage in Tablets and a Fixed-dose Combination Tablet in Healthy Participants [Completed]

Bioequivalence Study of Fixed Dose Combination of 2.5 mg Saxagliptin/850 mg Metformin Tablet Relative to 2.5 mg Onglyza and 850 mg Glucophage Tablets Co-Administered [Completed]

A Study to Evaluate the Effect of Multiple Doses of Isavuconazole on the Pharmacokinetics of Metformin [Completed]
The purpose of this study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of a single dose of metformin. Safety and tolerability of isavuconazole will be assessed alone and in combination with metformin.

A Study Comparing the Amount of Metformin and After Taking a Combination Tablet vs. Separate Tablets [Completed]

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Reports of Suspected Glucophage (Metformin) Side Effects

Renal Failure Acute (56)Lactic Acidosis (51)Blood Glucose Increased (37)Nausea (37)Diarrhoea (37)Vomiting (35)Hypoglycaemia (30)Hyperkalaemia (28)Fatigue (25)Renal Failure (22)more >>


Based on a total of 9 ratings/reviews, Glucophage has an overall score of 7.44. The effectiveness score is 7.56 and the side effect score is 7.11. The scores are on ten point scale: 10 - best, 1 - worst. Below are selected reviews: the highest, the median and the lowest rated.

Glucophage review by 57 year old female patient

Overall rating:  
Effectiveness:   Highly Effective
Side effects:   No Side Effects
Treatment Info
Condition / reason:   diabetes type 2
Dosage & duration:   250 ml (dosage frequency: once per day) for the period of about a year now
Other conditions:   osteopinia, menopause symptons
Other drugs taken:   Fosomax, HRT, Zoloft
Reported Results
Benefits:   Lowering of blood sugar without risk of hypoglycemia
Side effects:   None
Comments:   For years I took 4 ml glimepiride daily for type 2 diabetes, but often awoke in the middle of the night due to hypoglycemia. Finally my doctor reduced my glimepiride to 2 ml daily and added 250 ml metformin daily. For me, this combination is very effective. It controls my blood sugar as well as the glimepiride alone without the concomitant hypoglycemia. I understand that some people with borderline type 2 diabetes control their sugar levels with metformin alone, and my doctor may try this if my glycohemoglobin blood tests (HbA1C) stay in the low 6s.


Glucophage review by 46 year old male patient

Overall rating:  
Effectiveness:   Considerably Effective
Side effects:   No Side Effects
Treatment Info
Condition / reason:   Diabetes
Dosage & duration:   850 mg / 500 mg taken x 3 times a day for the period of 5 years 7 months
Other conditions:   high blood pressure
Other drugs taken:   none
Reported Results
Benefits:   the benefits of the treatment were that the blood sugar level that were very high in the beginning of the treatment went to controlled level. (it is controlled with the use of the medicine. I do not know what happens if I stop taking the medicine.)taking the medicine also helps in controlling hunger and so it help in having three meals, on regular times.
Side effects:   no side effect that I have experienced or can tell about. I was told that the medicine may damage my kidneys and I am taking regular check ups to test kidney function, however after over 5 years of taking the medicine every day (three times a day) there are no side effect and no problems to the kidneys.
Comments:   the treatment is taking the medicine every day, three times a day for the first three years the dosage I got was of 850 mg twice a day one pill after breakfast and one pill after supper. after three years the dosage was changed a bit and I have received 500 mg three times a day, one pill after each meal. recently (round six months ago) since the blood sugar leveled were under control, the dosage was reduced to 500 mg twice a day after breakfast and after supper


Glucophage review by 45 year old male patient

Overall rating:  
Effectiveness:   Ineffective
Side effects:   Extremely Severe Side Effects
Treatment Info
Condition / reason:   Diabetes Type 2
Dosage & duration:   500mg daily taken 1 time a day for the period of 3 weeks
Other conditions:   Asthma
Other drugs taken:   Nexium, Albuterol
Reported Results
Benefits:   None that I could see. Made me very sick and weak.
Side effects:   Nausea,chills,difficulty breathing,indigestion,dizziness,lightheaded,tired,anxiety
Comments:   Prescribed about a month ago Recently diagnosed with Type 2 diabetes. Tried for the better part of three weeks. The side effects were mild at first, but intensified so much, I ended up in the ER. Stopped taking it two days ago and slowly regaining my strength.

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Page last updated: 2015-08-10

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