Metformin Use and Vitamin B12 Deficiency: Managing the Risks

The recent change in reimbursement for primary care services, led by Medicare’s value-based reimbursement model, makes cost containment paramount. This new framework emphasizes focusing on early prevention measures to minimize complications, decreasing and controlling cost, potentiating patient satisfaction, and implementing a team-based approach involving healthcare providers and patients. If effective evidence-based measures are utilized, providers receive greater reimbursement and patient health is maximized. A simple screening test and/or supplementation that improves quality of life, increases overall safety in the setting of peripheral neuropathy, reduces office visits secondary to neuropathic exacerbations, and provides relief from symptoms would be desirable.

The discrepancy between the cost of treating a patient with metformin-induced vitamin B₁₂ deficiency vs treating complications from neuropathy misattributed to diabetes is substantial. The blood test for monitoring vitamin B₁₂ levels costs approximately $50 at LabCorp and Quest Diagnostic labs.²³ If a provider deems vitamin B₁₂ supplementation medically necessary, the cost of 1000 mcg of oral vitamin B₁₂ supplements is approximately $18 for a 150-day supply²⁴ or about $36 per year. Additionally, a single-dose vial of injectable vitamin B₁₂ costs <$15 per injection.²⁵   

These numbers stand in stark contrast to the cost of treating the painful symptoms that result from peripheral neuropathy with gabapentin, pregabalin, duloxetine, tramadol, or amitriptyline (Table).²⁶  

Table. Cost of Medications to Treat Peripheral Neuropathy²⁶

Medication	Dose	Quantity	Average Retail Price
Gabapentin	100 mg 300 mg 400 mg 600 mg 800 mg	90 pills	$27.00 $95.00 $115.00 $169.00 $183.00
Pregabalin	25-300 mg	30 pills	$95.00
Duloxetine	20-60 mg	30 pills	$169.00
Tramadol	50 mg	30 pills	$22.00
Amitriptyline	10-100 mg	90 pills	$6.00

Furthermore, the cost of pharmaceuticals is the proverbial tip of the iceberg, since hospitalizations for micro- or macrovascular complications and their sequelae — such as infection, amputation, disability, etc — increase the cost of treatment exponentially and can soar into the billions. Recent research estimates the cost of care for type 1 diabetes mellitus annually at $0.3 to $1 billion and for T2DM at $4.3 to $12.7 billion, approximately 27% of which is due to medical care for peripheral neuropathy alone.²⁷ Up to 50% of patients aged >65 years with T2DM experience diabetes-induced peripheral neuropathy and of these, 10% to 20% have unremitting pain as a primary symptom that requires medication.²⁸ It is important to remember that the symptoms of neuropathy from B₁₂ deficiency are correctable if diagnosed early but become irreversible, like diabetes-induced neuropathy, if this diagnosis is missed.

To develop a successful standard of care with respect to treatment of metformin-induced vitamin B₁₂ deficiency, the medical community must establish clear parameters for the normal range of values of vitamin B₁₂ levels. The risk of developing low vitamin B₁₂ directly correlates with the dose of metformin and/or duration of use. Patients who take >1000 mg/d for >3½ years are 10 times more at risk for vitamin B₁₂ insufficiency than those taking <1000 mg/d for <3½ years.⁷ Low vitamin B₁₂ levels improve in patients using metformin who take multivitamins daily compared with those who do not.²⁹

From the May 01, 2019 Issue of Clinical Advisor