This work is a first attempt to understand the mechanism of metformin thermal decomposition under inert conditions. Thermal gravimetric analysis coupled with mass spectrometry was used to probe the thermal degradation reactions. Density functional theory and second-order perturbation (MP2) theoretical calculations were used to construct a reaction mechanism for metformin decomposition. It was evident that the reactions are initiated via formation of methyl radicals, and ammonia via 1.3-H shift, followed by a series of different secondary reaction pathways. The formation of cyanamide, dimethylamine and HCN were among the main secondary products. The proposed mechanism is important for future treatment of wastewater containing metformin and similar drugs formulations, and their possible conversion to useful commodities.