Metformin Compounding Legal Status: What Patients and Prescribers Need to Know

Is compounded metformin an FDA-approved drug?

No. FDA states that compounded drugs are not FDA-approved [1]. Approved metformin is a manufactured tablet: immediate-release tablets for adults and children 10 and older with type 2 diabetes, extended-release tablets for adults [2][3]. A compounded preparation is not one of those approved tablets.

What federal law says about compounders

The Drug Quality and Security Act, enacted November 27, 2013, updated federal compounding law and created a second category of compounder [1]. A traditional compounding pharmacy's exemption from FDA approval, current good manufacturing practice and adequate-directions labeling applies only when the law's conditions are met, one of which is that drugs are compounded based on valid patient-specific prescriptions [1].

An outsourcing facility is a voluntary category. It must follow current good manufacturing practice, is inspected by FDA on a risk-based schedule, must report adverse events and must give FDA information about the products it compounds, and it may distribute compounded drugs under a patient-specific prescription or a provider order for office stock [1]. FDA is also developing lists of bulk drug substances that can be used in compounding [1].

What the approved tablets' label covers

The label's boxed warning is for lactic acidosis, with risk factors including renal impairment, age 65 or older, contrast studies, surgery, hypoxic states such as acute congestive heart failure, excessive alcohol intake and hepatic impairment [2]. The label lists severe renal impairment (eGFR below 30 mL/min/1.73 m2) as a contraindication and says starting metformin is not recommended at an eGFR of 30 to 45 [2]. The labeled maximum is 2,550 mg per day in divided doses for immediate-release tablets and 2,000 mg once daily for extended-release tablets [2][3].

Off-label uses

The label indication is type 2 diabetes; use for prediabetes, PCOS and weight loss is off-label [2]. In the Diabetes Prevention Program, 3,234 adults with elevated glucose were randomized to placebo, metformin 850 mg twice daily or a lifestyle program. Metformin lowered diabetes incidence by 31% versus placebo over a mean 2.8 years [4].

NDMA recalls

FDA's metformin NDMA updates describe voluntary recalls of specific extended-release lots that may have contained N-nitrosodimethylamine above the acceptable intake limit, and state that FDA testing has not shown NDMA in immediate-release metformin [5].