Rapid Restoration of Circulating Vitamin B12 Levels by Using Oral Sucrosomial® Vitamin B12 in Metformin-Associated B12 Deficiency: Results from a Double-Blind, Placebo-Controlled Randomized Clinical Trial

<b>Background/Objectives:</b> Vitamin B12 deficiency is common in individuals with type 2 diabetes mellitus (T2DM) receiving long-term metformin therapy, primarily due to impaired intestinal absorption. Conventional oral B12 supplementation is often associated with delayed or inconsistent biochemical correction. A lipid-based Sucrosomial^® delivery system has been shown to improve circulatory vitamin B12 levels in healthy adults with deficiency, and the present study evaluates its performance in the clinically challenging context of metformin-treated individuals with T2DM, a population characterized by pharmacologically impaired intestinal vitamin B12 absorption. <b>Methods:</b> This multicentre, double-blind, placebo-controlled, parallel-group randomized clinical trial evaluated the efficacy, safety, and tolerability of a Sucrosomial^® vitamin B12 formulation in adults with T2DM receiving metformin and presenting with vitamin B12 deficiency. Participants were randomized (1:1) to receive oral Sucrosomial^® vitamin B12 (1000 µg daily; <i>n</i> = 25) or placebo (<i>n</i> = 25) for three weeks. Serum total vitamin B12 and holotranscobalamin (HoloTC), the biologically active fraction of vitamin B12, were assessed at baseline and during follow-up, with time-to-normalization and safety analyses performed. <b>Results:</b> Sucrosomial^® vitamin B12 supplementation resulted in rapid and sustained increases in circulating vitamin B12 levels, with early separation from placebo, and a substantially higher proportion of participants achieved normalization of serum vitamin B12 concentrations within the three-week period. Parallel improvements in HoloTC levels indicated enhanced biologically active vitamin B12 availability, and the intervention was well tolerated with no clinically relevant safety concerns. <b>Conclusions:</b> These findings demonstrate that an oral Sucrosomial^® vitamin B12 formulation can achieve rapid and reliable biochemical repletion of both total and biologically active vitamin B12 in metformin-treated adults with T2DM, despite pharmacologically impaired intestinal absorption, while maintaining a favourable safety and tolerability profile.