In rats fed a high-fat diet, the combination of dapagliflozin (5 mg/kg/day) and 16:8 intermittent fasting for 8 weeks reduces body weight by 29.5% and body mass index by 30.7% compared to high-fat diet controls, and normalizes adiposity index, liver size, and serum glucose levels more effectively than either intervention alone, through enhanced energy expenditure and reduced fat storage.

When the body is deprived of food for long periods and glucose is lost in urine, cells sense low energy and turn on AMPK, which activates SIRT1. SIRT1 turns off fat-making genes and turns on fat-burning and heat-producing pathways in fat tissue. It also fixes broken body clocks that were making the body store too much fat, and it restores gut bacteria that produce chemicals telling the brain to stop eating. Together, this reduces fat storage, burns more calories, and lowers blood sugar and liver fat.