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This sequential approach serves two purposes: first, to eliminate immortal time bias by properly aligning treatment initiation with follow-up start (T0) and, second, to maximize statistical power by allowing individuals to contribute data across multiple trials

For example, mice fed a high-fat diet for 21 days have both lipid and protein compositional changes in cellular plasma membranes that result in an impaired capacity for oxidative phosphorylation, increased reactive oxygen species (ROS) production, hepatosteatosis and insulin resistance (Shama et al., 2023)

These protective effects are thought to stem from maintaining cerebral energy homeostasis and mitigating metabolic stress (31)

Given the complexity of the clinical effects exhibited by DPP-4 inhibitors in diabetes, it may not be entirely informative to refer to them solely as incretin-based drugs

GS is potentially one such compound