Perfecting the Puzzle of Pathophysiology: Exploring Combination Therapy in the Treatment of Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a debilitating, lifelong condition with a rising incidence. A wide variety of antihyperglycemic agents are available on the market to treat diabetes. However, the number of patients living with diabetes under suboptimal control remains relatively high. This calls into question whether the application of the current treatment standards is effective and durable to truly manage the disease well. This paper aims to highlight the various classes of antihyperglycemic agents from a pathophysiologic perspective and explore the best possible combination that can have a durable effect on diabetes management. To determine this, an eight-piece pathophysiologic puzzle was created, each piece representing an organ system affected by the disease—liver, pancreas (alpha and beta cells), muscle, adipose tissue, gut, brain, and kidneys. Choosing a combination therapy that is both durable and can effectively address all eight pieces of the puzzle can theoretically create sustainable ameliorating effects. This combination can potentially lead to reduced microvascular and macrovascular complications, as well as work towards creating an ideal long-term, affordable diabetes care plan.