Miglitol

Metformin, the main biguanide in clinical settings, is the most common antidiabetic agent worldwide and has for years been regarded as a safe treatment option mostly for subjects with type II diabetes mellitus. Nevertheless, long-term metformin treatment leads to vitamin B12 and/or folic acid/folate deficiency in a significant portion of metformin recipients. As these deficiencies, and particularly in the case of vitamin B12, may lead to severe suboptimal health outcomes and are frequently encountered, the current review provides a comprehensive insight into the underlying mechanisms.

For this purpose, a literature search in PubMed and SCOPUS was conducted using appropriate keywords.

The mechanisms responsible for the deficiency have not thus far been fully elucidated. Early studies focused mainly on the impaired function of the intrinsic factor, responsible for the absorption of vitamin B12, and several intestinal brush border enzymes. The vitamin deficiency was found to be either temporary or else persistent. Recent studies point to the crucial role of several bacteria and their gut-host interactions, as several mechanisms were observed in experimental studies for the capture of vitamin B12 from the host. Other basic research studies found instead a redistribution of vitamin B12 without a remarkable effect on the total amount. The administration of calcium or miglitol has been found to constitute potential ways to compensate for the deficiencies observed.

A deeper understanding of the mechanisms driving this deficiency will pave the way to a causative treatment for and even prevention of this major side effect.

Introduction: Diabetes mellitus (DM) is a chronic metabolic disorder characterized by hyperglycemia due to impaired insulin secretion or resistance. Conventional treatments like acarbose, miglitol, and voglibose inhibit carbohydrate-digesting enzymes but often cause adverse effects and have bioavailability limitations. This has led to interest in plant-derived bioactive compounds as safer alternatives. Oleanolic and maslinic acids in Moroccan virgin olive oil have shown potent inhibitory activity against α-glucosidase and α-amylase, enzymes regulating postprandial glucose levels. Methods: This study quantified the levels of oleanolic and maslinic acids in olive oils from various Moroccan regions, considering factors such as olive variety, maturity index, production method, and geographic origin. Pharmacokinetic properties were assessed using in silico ADME analysis. Molecular docking was performed to evaluate inhibitory interactions with α-amylase and α-glucosidase. Molecular dynamics (MD) simulations (1000 ns) assessed complex stability, and MM-PBSA calculations determined binding free energies. Results: The concentrations of oleanolic and maslinic acids varied across olive oil samples. The Moroccan Picholine variety had the highest levels (58.3 mg/kg for maslinic acid and 55.06 mg/kg for oleanolic acid). Olive oil from the two-phase milling method contained higher concentrations than the three-phase system, and lower maturity index olives showed greater concentrations. Pharmacokinetic analysis indicated favorable drug-likeness properties for these bioactive compounds. In silico docking suggested notable binding of maslinic acid to α-amylase (-41.42 kJ/mol) and oleanolic acid to α-glucosidase (-32.22 kJ/mol), with interactions involving key amino acid residues. Molecular dynamics simulations indicated stable ligand-enzyme interactions, and MM-PBSA analysis estimated binding energies of -39.05±16.78 kJ/mol for the maslinic acid-α-amylase complex and -13.97±7.08 kJ/mol for the oleanolic acid-α-glucosidase complex. Conclusion: Moroccan virgin olive oil, rich in oleanolic and maslinic acids, may serve as a natural alternative for diabetes management by modulating key enzymatic pathways involved in glucose metabolism.