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

Journal article

Background/Objectives: 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. Methods: 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; n = 25) or placebo (n = 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. Results: 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. Conclusions: 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.

Authors: Conti, G; Kalo, AW; Ujjan, I; Aslam, A; Khan, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: MDPI
• Journal: Pharmaceutics
• Volume: 18
• Issue: 2
• Pages: 237
• Article number: 237
• Publication date: 2026-02-13
• Acceptance date: 2026-02-10
• DOI: 10.3390/pharmaceutics18020237
• EISSN: 1999-4923
• ISSN: 1999-4923
• Language: English
• Keywords: oral vitamin B12 delivery system; vitamin B12 deficiency; Sucrosomial® vitamin B12; metformin; type 2 diabetes mellitus