BOX WARNING Lactic Acidosis:
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during treatment with metformin hydrochloride extended-release tablets; 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 hydrochloride extended-release tablets and by use of the minimum effective dose of metformin hydrochloride extended-release tablets. In particular, treatment of the elderly should be accompanied by careful monitoring of renal function. Metformin hydrochloride extended-release tablet 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 hydrochloride extended-release tablets 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 hydrochloride extended-release tablets 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 extended-release tablets, since alcohol potentiates the effects of metformin hydrochloride on lactate metabolism. In addition, metformin hydrochloride extended-release tablets 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 extended-release 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 hydrochloride extended-release tablets, 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 hydrochloride extended-release tablets 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 hydrochloride extended-release tablets, 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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SUMMARY
METFORMIN HYDROCHLORIDE EXTENDED-RELEASE TABLETS
Rx only
Metformin hydrochloride extended-release tablets are an oral antihyperglycemic drug used in the management of type 2 diabetes.
Metformin hydrochloride extended-release tablets, as monotherapy, are indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes. Metformin hydrochloride extended-release tablets are indicated in patients 17 years of age and older.
Metformin hydrochloride extended-release tablets 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 Extended-Release (Metformin)
Metformin Still Best as First Type 2 Diabetes Treatment
Source: MedicineNet glipizide Specialty [2017.01.03]
Title: Metformin Still Best as First Type 2 Diabetes Treatment
Category: Health News
Created: 1/3/2017 12:00:00 AM
Last Editorial Review: 1/3/2017 12:00:00 AM
Pioglitazone, Sulfonylureas Safe and Effective in Type 2 Diabetes
Source: Medscape Diabetes & Endocrinology Headlines [2017.09.29]
They may not boast a cardiovascular benefit like other newer drugs, but these drugs can safely be added to metformin to manage type 2 diabetes.
Medscape Diabetes & Endocrinology
Another SGLT2 Inhibitor, Ertugliflozin, Meets Goals in Two Trials
Source: Medscape Diabetes & Endocrinology Headlines [2017.09.25]
In two phase 3 trials, the SGLT2 inhibitor ertugliflozin for the treatment of type 2 diabetes that is uncontrolled with metformin alone or with sitagliptin demonstrated safety and efficacy at 52 weeks.
Medscape Medical News
Published Studies Related to Metformin Extended-Release (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
Clinical Trials Related to Metformin Extended-Release (Metformin)
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.
Crossover Study to Evaluate the Comparative Bioavailability of Two Fixed Dose Combination Tablet Formulations of Extended Release Metformin and Extended Release Glimepiride in Health Volunteers [Terminated]
This is a an open-label, randomized, single dose, four-way crossover, multi-stage study
enrolling 20 healthy adult male and female subjects per part. This study consists of two
separate parts (Part A and B) with each part comprising four treatment periods. Each subject
will participate in all four treatment periods per part; Subjects may not enrol in both
Parts A and B.
This study is being conducted to compare the pharmacokinetics (PK) of two extended release
fixed dose combinations (FDC) oral formulations of metformin and glimepiride at two doses,
500mg/1mg and 1000mg/2mg, with each FDC formulation to be administered orally as a single
dose and compared with the commercially available formulations of metformin extended release
(XR) (GLUCOPHAGE ™ Sustained Release [SR]) and glimepiride immediate release (IR) (AMARYL
™).
Part A of study will evaluate the bioavailability of a formulation comprising a film coated
tablet containing release controlling polymers; and Part B will evaluate the bioavailability
of a formulation comprising a tablet coated with release controlling polymers.
In each part there will be 4 treatment periods. During each period, subjects will be
randomized sequentially to receive a single dose of a reference treatment of 500 mg
metformin XR / 1 mg glimepiride IR; and a reference treatment of 1000 mg metformin XR / 2 mg
glimepiride IR; and an FDC tablet containing 500 mg metformin XR and 1 mg glimepiride XR;
and an FDC tablet containing 1000 mg metformin XR and 2 mg glimepiride XR. Serial PK sampling
for up to 36 hours and safety assessments will be performed. Each period will be separated
by a washout period of at least 5 days and a follow-up visit will occur 14 days after the
last dose of study drug.
A Study Comparing the Amount of Metformin and After Taking a Combination Tablet vs. Separate Tablets [Completed]
An Extension Protocol to Evaluate Dose Comparisons of Leucine-Metformin Combinations in Type 2 Diabetic Patients [Active, not recruiting]
Study NS-0100-01E is an extension of Study NS-01-0100 designed to assess safety and longer
term effect (i. e., additional 8 weeks) of various fixed-dose leucine and metformin
combinations (NS-0100) versus standard metformin monotherapy on glycemic control in subjects
with type 2 diabetes using HbA1c as the primary endpoint.
Clinical Trial to Evaluate Safety and pK Profile of Metformin Glycinate in Healthy Volunteers [Completed]
Metformin Glycinate is a novel biguanide compound developed as a potential candidate for the
treatment of type 2 diabetes. Metformin Glycinate was found to improve metabolic control in
naive patients with type 2 diabetes.
The objective of this study is to evaluate the safety, tolerability and pK profile of
Metformin Glycinate 620 mg QD, 1240 mg QD, 2480 mg QD, after administration of one single
dose, in step A. In step A will be included 25 volunteers.
In step B the objective is to evaluate Safety, tolerability and pK profile of Metformin
Glycinate 620 mg BID, after administration of multiple dose during 8 days. In step B will be
included 24 volunteers.
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PATIENT REVIEWS / RATINGS / COMMENTSBased on a total of 1 ratings/reviews, Metformin Extended-Release has an overall score of 10. The effectiveness score is 10 and the side effect score is 10. The scores are on ten point scale: 10 - best, 1 - worst.
| | Metformin Extended-Release review by 46 year old female patient | | | Rating |
| Overall rating: | |  |
| Effectiveness: | | Highly Effective |
| Side effects: | | No Side Effects | | |
Treatment Info |
| Condition / reason: | | diabetes |
| Dosage & duration: | | 500 mg taken once a day in the morning for the period of have been on it for 12 months |
| Other conditions: | | sarcoidosis, depression, anxiety |
| Other drugs taken: | | plaquenil, paxil, trazodone | | |
Reported Results |
| Benefits: | | The drug significantly lower my blood glucose level. Currently my blood glucose runs an average of 115 with some days below 90. |
| Side effects: | | Although it is supposed to have a side effect of diarrhea I have been fortunate. I make sure I take with food. Sometimes if I dont have enough food on my stomach it may cause some upset but nothing terrible. Otherwise I have not had any other side effect.s |
| Comments: | | I take one tablet in the morning after or with my breakfast. So far no additional dosage is required. |
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Page last updated: 2017-09-29
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