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Modern diabetes management has largely focused on increasing insulin availability rather than restoring its physiological timing. This has led to widespread use of long-acting insulin secretagogues that impose continuous β-cell stimulation, often irrespective of metabolic demand. While effective in lowering glucose levels, such strategies may contribute to β-cell exhaustion, functional decline, and premature loss of endogenous insulin capacity.This hypothesis proposes that repaglinide, a short-acting meglitinide, represents a missed therapeutic opportunity due to its unique ability to restore temporal alignment of insulin secretion with meal-related glucose excursions. Unlike prolonged secretagogues, repaglinide induces rapid, short-duration insulin release that closely mimics physiological first-phase insulin response. This may reduce β-cell stress, preserve insulin synthesis and storage capacity, and improve metabolic efficiency.The hypothesis further reinterprets apparent “oral hypoglycemic failure” as a disorder of timing rather than absolute insulin deficiency, and positions repaglinide as a potential agent for preserving endogenous insulin opportunity. Cardiovascular and renal safety considerations are also integrated into this framework. This hypothesis re-evaluates repaglinide as a temporally aligned insulin secretagogue that restores physiological insulin release patterns rather than enforcing continuous secretion. It proposes that repaglinide reduces β-cell stress, preserves insulin manufacturing and storage capacity, and improves metabolic efficiency. The framework introduces a timing-based reinterpretation of oral hypoglycemic failure and positions repaglinide as a potential tool for preserving endogenous insulin opportunity in Type 2 Diabetes Mellitus. Cardiovascular and renal safety considerations are also discussed. This concept is based on the author’s clinical observations and theoretical exploration of insulin timing, β-cell physiology, and metabolic regulation.Dr. Aditya Bikram Mishra, MD (Medicine)Senior Fellow in Diabetes (IDF)Dibya Aditya Diabetes Care, Cuttack “Repaglinide does not increase insulin—it restores its timing.”“Modern therapy floods insulin—Repaglinide whispers it at the right moment.” Keywords RepaglinideMeglitinideTemporal insulin alignmentβ-cell preservationFirst-phase insulin secretionPostprandial hyperglycemiaInsulin timing physiologyType 2 diabetes mellitusOral hypoglycemic failureEndogenous insulin utilizationSecretagogue pharmacodynamicsβ-cell stress and exhaustionNeuroendocrine metabolic regulation