Table 1.
Settings, designs, and results of studies that investigated the impact of metformin-induced low vitamin B12 on peripheral neuropathy in T2DM patients.
| Study | Setting | Design | Results |
|---|---|---|---|
| Wile and Toth [15] | Neuromuscular clinic at a university hospital, Canada | Case-control study. Cases were T2DM patients on metformin with primary diagnosis of PN (59 participants). Controls were T2DM patients not taking metformin with primary diagnosis of PN (63 participants). | The metformin group had more severe PN (assessed by TCSS and NIS). Electrophysiological markers showed no significant difference between the two groups. Cumulative metformin dose showed a significant positive correlation with TCSS scores (rho = 0.80) and NIS scores (rho = 0.79). |
| Singh et al. [16] | Internal medicine clinic in a tertiary hospital, India | Cross-sectional study. Randomly selected T2DM patients were divided into metformin users (84 participants) and nonusers (52 participants). | The metformin group had more severe PN (assessed by TCSS). Cumulative metformin dose revealed a significant positive correlation with TCSS (rho = 0.53). |
| de Groot-Kamphuis et al. [17] | Secondary care outpatient diabetes clinic, the Netherlands | Cross-sectional study. Randomly selected T2DM patients were divided into metformin users (164 participants) and nonusers (134 participants). | Prevalence of neuropathy (obtained from records) was significantly lower in the metformin group. |
| Chen et al. [13] | Diabetes clinic of a tertiary hospital, UK | Cross-sectional study. Randomly selected T2DM patients were divided into metformin users (152 participants) and nonusers (50 participants). | All PN-assessing tools (monofilament, neurothesiometry, NTSS-6, and s-LANSS) showed no significant differences between the two groups. |
| Biemans et al. [18] | Four primary care centers, the Netherlands | Cross-sectional study. Metformin-treated T2DM patients were divided into the vitamin B12-deficient (126 participants) and normal (322 participants) groups. | There were no significant differences in PN (assessed by MNSI and extracted from records) between the two groups. |
| Russo et al. [19] | Diabetes clinic of a university hospital, Italy | Cross-sectional study. T2DM patients were divided into metformin users (124 participants) and nonusers (139 participants). | There was no significant difference in prevalence of PN between the two groups. PN was suspected based on abnormalities of certain evaluations and confirmed by NCVs. |
| Roy et al. [20] | Tertiary Hospital, India | Cross-sectional study. T2DM patients were divided into (1) the metformin group (35 participants), (2) the metformin + other antihyperglycemic group (20 participants), and (3) the nonmetformin group (35participants). | Neuropathy (assessed by NCVs) did not differ significantly between the groups. |
| Ahmed et al. [14] | Diabetes clinics of two tertiary hospitals, South Africa | Cross-sectional study. Metformin-treatedT2DM patients were divided into the vitamin B12-deficient (34 participants) and normal (87 participants) groups. | There was no difference in the presence of PN (assessed by NTSS-6) between the two groups. Levels of vitamin B12 and NTSS-6 scores were not correlated. |
MNSI: Michigan Neuropathy Screening Instrument; NCVs: nerve conduction velocities; NIS: Neuropathy Impairment Score; NTSS-6: Neuropathy Total Symptom Score-6; PN: peripheral neuropathy; rho: Spearman's rank correlation coefficient; s-LANSS: Self-administered Leeds Assessment of Neuropathic Symptoms and Signs; TCSS: Toronto Clinical Scoring System.