Should changes be made to lisinopril (angiotensin-converting enzyme inhibitor) or metformin (biguanide) in a patient with angular cheilitis and vitamin B12 deficiency?

From the Guidelines

For a patient with angular cheilitis associated with B12 deficiency who is taking lisinopril and metformin, I would recommend addressing the B12 deficiency directly rather than modifying these medications initially. Start B12 supplementation, typically with oral cyanocobalamin 1000-2000 mcg daily for at least 1-2 months, then consider maintenance dosing of 1000 mcg daily or weekly based on follow-up B12 levels. Metformin is known to reduce B12 absorption through several mechanisms including alterations in calcium-dependent uptake in the ileum, so long-term metformin users are at higher risk for B12 deficiency, as noted in the 2025 standards of care in diabetes 1. While it's reasonable to continue metformin if clinically indicated, ensure regular B12 monitoring (annually) for patients on long-term therapy, as suggested by the 2023 standards of care in diabetes 1. Lisinopril is not significantly associated with B12 deficiency and typically wouldn't need adjustment. Topical treatment for the angular cheilitis with antifungal agents like clotrimazole or nystatin may provide symptomatic relief while addressing the underlying B12 deficiency. If B12 supplementation and topical treatment don't resolve symptoms within 2-4 weeks, then consider further evaluation for other contributing factors. Some key points to consider in the management of metformin and B12 deficiency include:

• Metformin's association with B12 deficiency is well-documented, with studies suggesting a higher risk of deficiency with long-term use 1.
• Regular monitoring of B12 levels is recommended for patients on long-term metformin therapy, especially those with anemia or peripheral neuropathy 1.
• The choice of pharmacologic agents should be guided by a patient-centered approach, considering factors such as efficacy, hypoglycemia risk, and patient preferences 1.

From the FDA Drug Label

1. 2 Vitamin B12 Deficiency In metformin hydrochloride tablets clinical trials of 29-week duration, a decrease to subnormal levels of previously normal serum vitamin B 12 levels was observed in approximately 7% of patients Such decrease, possibly due to interference with B 12 absorption from the B 12-intrinsic factor complex, may be associated with anemia but appears to be rapidly reversible with discontinuation of metformin hydrochloride tablets or vitamin B 12 supplementation

• The patient has angular cheilitis with B12 deficiency.
• Metformin may be associated with Vitamin B12 deficiency.
• The FDA recommends managing any abnormalities in vitamin B12 levels, which may include discontinuation of metformin or vitamin B12 supplementation.
• No direct information is provided about lisinopril in relation to Vitamin B12 deficiency or angular cheilitis.
• Considering the potential link between metformin and Vitamin B12 deficiency, it may be necessary to monitor vitamin B12 levels and consider supplementation or discontinuation of metformin if the deficiency persists or worsens 2.
• No changes to lisinopril are directly indicated based on the provided information.

From the Research

Angular Cheilitis and Vitamin B12 Deficiency

• Angular cheilitis is a common inflammatory disorder of the lips, and its treatment depends on the underlying cause 3, 4.
• Vitamin B12 deficiency is a known cause of angular cheilitis, and its management involves supplementation with high-dose vitamin B12 5, 6.

Medication-Related Causes

• Metformin use for more than four months is a risk factor for vitamin B12 deficiency 5.
• There is no direct evidence to suggest that lisinopril causes angular cheilitis or vitamin B12 deficiency.
• However, it is essential to consider the patient's overall medication regimen and potential interactions when managing angular cheilitis and vitamin B12 deficiency 7.

Treatment Approach

• Treatment of angular cheilitis involves addressing the underlying cause, which in this case is vitamin B12 deficiency 4, 7.
• Supplementation with high-dose vitamin B12 (1 to 2 mg daily) is recommended to correct the deficiency 5.
• It may be necessary to review the patient's medication regimen, including metformin, to minimize the risk of vitamin B12 deficiency 5.