Effect Of Thiamine Pyrophosphate as an Adjunct to Metformin in Type 2 Diabetes: A Randomized, Controlled Pilot Clinical Trial

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by persistent hyperglycemia and an increased risk of cardiovascular and microvascular complications. Functional thiamine deficiency and altered activity of thiamine-dependent enzymes have been implicated in the metabolic dysregulation associated with diabetes. Thiamine pyrophosphate (TPP), the biologically active form of vitamin B1, plays a central role in mitochondrial glucose metabolism and may contribute to improved metabolic control. A randomized, placebo-controlled pilot clinical trial was conducted to evaluate the effect of TPP as an adjunct treatment to metformin in patients with T2DM with inadequate glycaemic control. Twenty-seven participants receiving stable metformin therapy were randomly assigned to receive weekly intravenous TPP or placebo for 12 weeks. Anthropometric, hemodynamic, and biochemical variables were assessed, including glycated haemoglobin (HbA1c), fasting glucose, and lipid profile. Inflammatory markers were also analysed. Both within-group and between-group statistical analyses were performed. Results: Twenty-seven patients were included in the final analysis. The intervention group showed a significant reduction in HbA1c (-7.4%, p = 0.003) and systolic blood pressure (-5.3%, p = 0.032). Other metabolic and inflammatory parameters showed favourable trends without reaching statistical significance. The intervention was well tolerated, and no serious adverse events were reported. Adjunctive therapy with thiamine pyrophosphate demonstrated promising effects on glycaemic control and hemodynamic parameters in patients with T2DM treated with metformin. These findings support the need for larger randomized clinical trials to confirm the potential therapeutic role of TPP in diabetes management.