467-P: The Relationship between Diabetic Peripheral Neuropathy and Metformin Treatment in Type 2 Diabetes Mellitus

Abstract

Background: Metformin is the first-line therapy for the treatment of Type 2 diabetes mellitus (T2DM) . However, the use of metformin may lead to neuropathy by affecting the absorption of vitamin B12. Our objective was to explore the association between the application of metformin and diabetic peripheral neuropathy (DPN) . Methods: The multicenter randomized cross-sectional study was conducted in 13 hospitals in Beijing from October 2015 to April 2016. T2DM Patients were divided into confirmed DPN group, suspected DPN group and non-DPN group by the five physical examinations (Ankle reflex, acupuncture pain, temperature, vibration, and pressure) . Non-parametric Mann-Whitney test was used for the comparison between non-normally distributed variables between two groups. Chi-square test was used for the comparison of categorical variables. The risk factors of DPN in T2DM Patients were assessed using logistic regression. Results: Compared with patients without metformin, patients taking metformin were more likely to suffer from DPN and suspected DPN (P < 0.0for both) . Similar results were obtained after stratifying the data based on age, BMI, and HbA1c. It was shown that the application of metformin was a risk factor for DPN (OR = 5.06, 95%Cl: 3.90-6.56; P < 0.001) and suspected DPN (OR = 3.58, 95%Cl: 2.78-4.62; P < 0.001) in T2DM patients after the adjustment for age, BMI and HbA1c. In addition, prolonged application of metformin, increased cumulative and single doses would also be associated with the risk of DPN (P < 0.0for all) . Conclusion: The application of metformin was observed relate to DPN in T2DM patients. The vitamin B12 concentration and peripheral nerve function of T2DM patients with the application of metformin should be monitored. Disclosure Q.Pan: None. J.Luo: None. L.Guo: None. Funding National Key R&D Program of China (2020YFC2009006)

Neuropathy of diabetes following initiation of a low-carbohydrate diet: Case report

“…A cross-sectional study by Pan et al. found a greater prevalence of TIND in patients with T2D taking metformin especially with prolonged use and higher doses [ 32 ]. A comparison of patients with T2D treated with metformin versus non-metformin treated patients found a higher incidence of TIND in the metformin group especially with higher doses (>2g), longer duration (>4 years), and low vitamin B12 levels [ 33 ].…”

Peripheral Neuropathy: A review of mechanism-based treatments with a focus on metformin as a possible choice

“…However, the outcomes of studies, using Metformin as symptomatic treatment of diabetic neuropathy, is not consistent with pre-clinical studies. Many studies have mentioned that vitamin B12 deficiency caused by Metformin use in diabetic patients can cause and even worsen diabetic neuropathy and should be carefully noticed in diabetic population [49][50][51][52][53][54].…”

“…Luo et al also mentioned that Metformin administration in type 2 DM patients was associated with higher incidence of developing diabetic PN. They named prolong use, higher cumulative dose of Metformin and male sex as the major risk factors for developing PN [53].…”

“…However, there are concerns about using Metformin as an adjuvant for the treatment of PN. To date, many clinical studies suggested that long-term use of Metformin, especially over 5 years and higher cumulative dose of Metformin is associated with vitamin B12 deficiency, which can cause progression of central and peripheral neuropathy [49][50][51][52][53][54]. Contrary to initial disappointing results, Russo et al mentioned that in type 2 DM patients who received Metformin for at least 6 months, vitamin B12 deficiency was just mild and didn't have a relationship with developing diabetic neuropathy [76].…”