INS and diabetes mellitus: Metformin exerts its effects by suppressing appetite, reducing insulin secretion, and improving gut microbiota.33 Sodium-glucose cotransporter-2 inhibitors directly reduce body weight by increasing glucose excretion in the kidneys.34 The DiRECT study confirmed that diabetes can be partially reversed through weight loss and proposed the “double cycle hypothesis,” suggesting that type 2 diabetes results from fat infiltration into the liver, pancreas, and muscle tissue, leading to the destruction of pancreatic β cells and tissue insulin resistance.