TYPE 2 diabetes mellitus (T2D) continues to affect millions worldwide, with diabetic peripheral neuropathy (DPN) representing one of its most debilitating complications. Despite standard approaches focusing on glycaemic control and symptomatic relief, long-term outcomes remain suboptimal for many patients. Recent evidence suggests that combining dapagliflozin, a sodium-glucose co-transporter 2 (SGLT-2) inhibitor, with methylcobalamin, the active form of vitamin B12, may offer an enhanced treatment pathway. In a key finding, this combination significantly improved both nerve function and glycaemic measures without increasing the risk of adverse events.
The systematic review analysed randomised controlled trials (RCTs) published up to 30 September 2024, investigating the efficacy and safety of dapagliflozin combined with methylcobalamin in treating DPN in adults with T2D. Seven RCTs met the inclusion criteria. Data were extracted and statistically analysed using RevMan 5.4 software, with the Cochrane Risk of Bias 2.0 tool applied to assess study quality. Primary outcomes included the overall effective rate (OER), various nerve conduction velocities (motor and sensory), fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), glycosylated haemoglobin (HbA1c), and incidence of adverse events.
The combination therapy showed significant benefits across multiple domains. The OER was notably improved (OR: 5.05; 95% CI: 2.60–9.81). Improvements in nerve function were seen with increases in CPMNCV (MD: 3.93 m/s), CPSNCV (MD: 3.36 m/s), MMNCV (MD: 4.71 m/s), and MSNCV (MD: 3.05 m/s), (all p<0.01). Glycaemic outcomes also improved, including FPG (MD: –1.19 mmol/L), 2hPG (MD: –1.36 mmol/L), and HbA1c (MD: –0.87%), each statistically significant. Importantly, no significant rise in adverse events was observed (OR: 0.37; 95% CI: 0.07–2.03; p=0.25).
These findings suggest that dapagliflozin combined with methylcobalamin may offer a clinically meaningful advance in the management of DPN among patients with T2D. The dual effect on neuropathic improvement and glycaemic control presents a potentially valuable therapeutic approach in routine practice. However, the evidence base remains limited by the small number of high-quality trials and variations in study design. Larger, multi-centre trials with longer follow-up periods are needed to confirm long-term efficacy and safety. Until then, clinicians should consider this combination as a promising option within an individualised care plan for patients with DPN.
Reference
Deng X et al. Dapagliflozin combined with methylcobalamin in the treatment of type 2 diabetes mellitus with peripheral neuropathy: a systematic review and meta-analysis. Front Endocrinol (Lausanne). 2025;16:1514783.
