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Dapagliflozin plus methylcobalamin improved nerve function and glucose control in diabetic neuropathy.

A study published in the June 2025 issue of Frontiers in Endocrinology underscored that type 2 diabetes mellitus (T2DM) frequently resulted in diabetic peripheral neuropathy, with existing therapeutic strategies offering suboptimal long-term outcomes despite targeting glycemic regulation and symptom control.  

Researchers evaluated the efficacy and safety of combining dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, with methylcobalamin in the management of diabetic peripheral neuropathy.  

They synthesized randomized controlled trials (RCTs) from major databases published up to September 30, 2024, assessing the combined use of dapagliflozin and methylcobalamin for treating diabetic peripheral neuropathy (DPN) in individuals with type 2 diabetes mellitus (T2DM). The statistical analysis was performed using RevMan 5.4 and evaluated the risk of bias with the Cochrane Risk of Bias 2.0 tool (ROB 2.0). The evaluated outcomes included overall effective rate (OER), common peroneal motor nerve conduction velocity (CPMNCV), common peroneal sensory nerve conduction velocity (CPSNCV), median motor nerve conduction velocity (MMNCV), median sensory nerve conduction velocity (MSNCV), fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA_1c), and rate of adverse events (RAE).  

The results showed that 7 RCTs met the inclusion criteria. The combination of dapagliflozin and methylcobalamin significantly improved the OER [odds ratio (OR): 5.05; 95% CI: 2.60–9.81], CPMNCV [ MD: 3.93 m/s; 95% CI: 2.16–5.70; P<0.01], CPSNCV [MD: 3.36 m/s; 95% CI: 2.74–3.98; P<0.01], MMNCV [MD: 4.71 m/s; 95% CI: 3.90–5.52; P<0.01], and MSNCV [MD: 3.05 m/s; 95% CI: 2.19–3.90; P<0.01]. The FPG [MD: -1.19 mmol/L; 95% CI: -1.40 to -0.98; P<0.01], 2hPG [MD: -1.36 mmol/L; 95% CI: -1.44 to -1.27; P<0.01], and HbA_1c [MD: -0.87%; 95% CI: -1.04 to -0.71; P<0.01] levels decreased significantly. No significant increase in the RAE was found [OR: 0.37; 95% CI: 0.07–2.03; P=0.25].  

Investigators concluded that dapagliflozin combined with methylcobalamin had effectively enhanced nerve conduction and glycemic control without increasing adverse events in individuals with DPN and T2DM. 

Source: frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2025.1514783/full