Metformin Compassionate Use and Expanded Access: How to Get It When Cost or Coverage Is a Barrier

Is metformin available through compassionate use?

Metformin is sold as a generic prescription drug indicated for type 2 diabetes [1]. The one report found that uses the phrase compassionate use concerned insulin-dextrose treatment for metformin poisoning in four intensive-care patients, not access to metformin [4].

Which uses the label covers, and which it does not

Immediate-release metformin hydrochloride tablets are labeled as an adjunct to diet and exercise to improve glycemic control in adults and in children 10 and older with type 2 diabetes [1]. Extended-release tablets are labeled for adults with type 2 diabetes [2]. Prediabetes prevention, PCOS and weight loss are not labeled indications [1]. Prediabetes was studied in the Diabetes Prevention Program: in 3,234 adults without diabetes but with elevated glucose, metformin 850 mg twice daily reduced diabetes incidence by 31% versus placebo over a mean 2.8 years, compared with 58% for intensive lifestyle change [5].

What the label requires before and during treatment

The immediate-release label calls for an eGFR before starting and at least yearly. It lists metformin as contraindicated below 30 mL/min/1.73 m2, says starting is not recommended at 30 to 45, and says to discontinue it if eGFR later falls below 30 [1]. The label also calls for vitamin B12 measurement every 2 to 3 years and annual hematologic testing; in 29-week trials, previously normal B12 levels fell to subnormal in approximately 7% of patients [1]. For iodinated contrast procedures, the label says to stop metformin at the time of or before the procedure in patients with eGFR 30 to 60, a history of hepatic impairment, alcoholism or heart failure, or intra-arterial contrast, and to re-evaluate eGFR 48 hours afterward before restarting [1]. The boxed warning names the risk factors for metformin-associated lactic acidosis: renal impairment, certain drugs such as carbonic anhydrase inhibitors, age 65 or older, contrast studies, surgery and other procedures, hypoxic states, excessive alcohol intake, hepatic impairment and mitochondrial disease [1].

Extended-release NDMA recalls

Between July 2020 and January 2021 the FDA announced voluntary recalls of extended-release metformin products, including lots from Marksans, Sun (Riomet ER oral suspension), Bayshore and Nostrum, because some lots contained or may have contained N-nitrosodimethylamine above the acceptable intake limit [3]. FDA testing has not shown NDMA in immediate-release metformin, the most commonly prescribed type [3].