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The difference lies in caloric deficit sustainability

The tubular proximal reabsorption of sodium is mainly mediated by the Na + /H + exchanger isoform 3 (NHE3), a protein located in the brush-border epithelium of the proximal tubule ( Figure 2 )

Although what constituted reasonable may have changed over time, what remained constant was the triad upon which we depended to achieve this: insulin, metformin and sulfonylureas