Metformin Adherence Linked to Lower Risk of Diabetic Polyneuropathy: Study
Written By : Medha Baranwal
Medically Reviewed By : Dr. Kamal Kant Kohli
Published On 2026-07-02 03:45 GMT | Update On 2026-07-02 03:45 GMT
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Taiwan: Researchers have found in a large study involving nearly 360,000 patients with type 2 diabetes that consistent adherence to metformin therapy was associated with a significantly lower risk of developing diabetic polyneuropathy. Patients who regularly took metformin also experienced fewer neuropathy-related complications, including diabetic foot ulcers and limb amputations.
These findings suggest that long-term metformin use may provide neuroprotective benefits beyond its glucose-lowering effects. However, because prolonged metformin therapy can contribute to vitamin B12 deficiency, routine monitoring of vitamin B12 levels is recommended in chronic users.
The findings, published in Metabolic Syndrome and Related Disorders by Ying-Hsuan Tai and colleagues, examined whether continued metformin use influences the risk of diabetic polyneuropathy in patients with type 2 diabetes receiving second-line glucose-lowering therapy. The study was prompted by concerns that long-term metformin use may contribute to vitamin B12 deficiency, a known risk factor for neuropathy.
Using real-world data from the TriNetX network, researchers compared patients who remained adherent to metformin with those who did not, based on prescription claims. Polyneuropathy was identified through diagnostic records and nerve conduction studies.
After matching for baseline characteristics, the primary analysis included 58,027 patients in each group. Compared with metformin-adherent patients, those who were nonadherent had a significantly higher risk of developing polyneuropathy, along with a greater likelihood of neuropathy-related complications and adverse outcomes.
The findings remained consistent across multiple sensitivity analyses and were independently validated in Taiwan’s National Health Insurance Research Database, which included 31,384 matched patient pairs. The validation cohort confirmed the association between metformin nonadherence and an increased risk of polyneuropathy.
Key findings from the study include:
- Patients who did not adhere to metformin therapy had a 26% higher risk of developing polyneuropathy compared with adherent patients.
- Nonadherence was associated with an increased risk of diabetic foot ulcers.
- The risk of lower-limb amputation was higher among patients who discontinued or inconsistently used metformin.
- Use of medications prescribed for neuropathic symptoms was more common in the nonadherent group.
- Nonadherent patients also experienced a greater risk of bone fractures.
- Similar results were observed in the independent validation cohort, supporting the robustness of the findings.
The authors concluded that maintaining metformin therapy after the initiation of second-line diabetes treatment may help reduce the risk of diabetic polyneuropathy and its complications. They also suggested that strategies such as vitamin B12 supplementation could potentially enhance these benefits.
Given the known relationship between long-term metformin use and vitamin B12 deficiency, the researchers emphasized the importance of regular monitoring and appropriate supplementation when needed to optimize patient outcomes.
Reference:
Tai, Y. H., Lee, H. Y., Huang, P. H., Chen, W. T., Chien, L. N., Chan, L., & Hong, C. T. Metformin Adherence and Risk of Polyneuropathy in Type 2 Diabetes Mellitus: An International Matched Cohort Study with Independent Validation. Metabolic Syndrome and Related Disorders. https://doi.org/10.1177_15578518261454613
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