FDA Issues New Guidelines For Metformin Use In Kidney Patients

A drug safety announcement was made by FDA on April 8, 2016, requiring some labeling changes in the medications containing metformin. It is an anti-diabetic drug and FDA wants to expand its use in patients with impaired renal functions.

The current labeling prohibits the use of metformin in the patients with abnormal kidney functions as it may cause development of lacto-acidosis in them. In a couple of petitions, FDA was asked to review some of the medical studies on metformin. The studies contained the safety data regarding the use of metformin in patients with mild to moderate renal impairment. As a result of the review of various studies, FDA changed the drug labeling, stating the use of the measure of kidney function to ascertain whether to prescribe metformin containing medications to a particular patient or not. All the metformin containing drugs have to reflect this new information.

These changes in the labels were the result of a research in which diabetic patients treated with metformin tolerate the drug and may continue taking it, even with mild renal impairment. It was also observed that there was no reason why patients with CHD, CHF, and COPD should discontinue this drug. In another research, it was observed that metformin does not increase the risk of lacto-acidosis. Another research on metformin demonstrated lower risks than insulin for cardiovascular diseases and lower risk of mortality when compared with other oral hypoglycemic agents in 51, 675 patients followed for four years. Patients with renal impairment showed no increased risk of cardiovascular disease.

Metformin acts as an insulin sensitizer and reduces hepatic glucose production. It increases at least two times in patients with type 2 diabetes. The glucose decreasing effects of metformin are chiefly due to reduced hepatic glucose output (mainly through gluconeogenesis and to a lesser extent, glycogenolysis inhibition) and increased insulin dependent glucose uptake in skeletal muscles. It decreases fasting plasma glucose concentrations by 25-30%.

The actual mechanism through which metformin decreases hepatic glucose production is still unclear, but its most probable site of action is hepatocyte mitochondria where it stops respiratory chain oxidation of complex substrates. Metformin is best in treating type 2 diabetes because it has no risk of hypoglycemia even at high doses and can be used in overweight patients.

In 2014, approximately 14.4 million patients received prescriptions for metformin containing medications from US retail pharmacies. Since, metformin was approved in 1995 by FDA, it is contraindicated in some patients with renal dysfunction. FDA reviewed different publications in the medical literature showing that metformin use may be safe in patients with mild to moderate renal impairment. Moreover, further study of published population based study data on metformin containing products both in the United States and abroad indicates that metformin is also used clinically outside of the current labeling indications and it is prescribed to patients with mild to moderate and chronic kidney diseases.

Metformin containing medicines are prescription only medications and they are used along with diet and exercise to lower blood sugar levels in patients with type 2 diabetes. Antidiabetic medications containing metformin are available both as single ingredient products and also in combination with other drugs. FDA approved metformin containing medications include Actoplus Met (metformin and pioglitazone), Actoplus Met XR (metformin and pioglitazone extended release), Avandamet (metformin and rosiglitazone), Fortamet (metformin extended release), Glucophage (metformin), Glucophage XR (metformin extended release), Glucovance (metformin and glyburide), Glumetza (metformin extended release), Invokamet (metformin and canagliflozin), Janumet(metformin and sitagliptin), Janumet XR (metformin and sitagliptin extended release), Jentadueto (metformin and linagliptin), Kazano (metformin and alogliptin), Kombiglyze XR (metformin and saxagliptin, extended release), Prandimet (metformin and repaglinide), Riomet (metformin), Synjardy (metformin and empagliflozin), Xigduo XR (metformin and dapagliflozin extended release).

Health care professionals should follow the latest guidelines while prescribing metformin containing medications to the patients with dysfunctional kidneys. They must consider parameters like blood creatinine concentration and glomerular filtration rate (eGFR) in estimating patient’s kidney functions before prescribing metformin containing medications. Moreover, they must also encourage the patients to read Medication Guide insert before taking metformin containing drugs.

Patients should talk to their physicians if they have any queries regarding metformin. They should inform their prescriber about any type of kidney problems faced before and during the therapy.

Any kind of adverse events (effects) involving metformin containing drugs should be directly reported to the FDA MedWatch program.

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