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2026
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| Online Access: | https://doi.org/10.5281/zenodo.19158518 |
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| author | Mishra, Aditya |
| author_facet | Mishra, Aditya |
| contents | <p>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.<br>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.<br>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.</p> <p>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.</p> <p>This concept is based on the author’s clinical observations and theoretical exploration of insulin timing, β-cell physiology, and metabolic regulation.<br>Dr. Aditya Bikram Mishra, MD (Medicine)<br>Senior Fellow in Diabetes (IDF)<br>Dibya Aditya Diabetes Care, Cuttack</p> <p>“Repaglinide does not increase insulin—it restores its timing.”<br>“Modern therapy floods insulin—Repaglinide whispers it at the right moment.”</p> <p>Keywords </p> <p>Repaglinide<br>Meglitinide<br>Temporal insulin alignment<br>β-cell preservation<br>First-phase insulin secretion<br>Postprandial hyperglycemia<br>Insulin timing physiology<br>Type 2 diabetes mellitus<br>Oral hypoglycemic failure<br>Endogenous insulin utilization<br>Secretagogue pharmacodynamics<br>β-cell stress and exhaustion<br>Neuroendocrine metabolic regulation</p> |
| format | Recurso digital |
| id | zenodo_https___doi_org_10_5281_zenodo_19158518 |
| institution | Zenodo |
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| publishDate | 2026 |
| publisher | Zenodo |
| record_format | zenodo |
| spellingShingle | Repaglinide Revisited: A Temporal Insulin Alignment Hypothesis for β-Cell Preservation and Metabolic Efficiency in Type 2 Diabetes Mellitus Mishra, Aditya <p>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.<br>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.<br>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.</p> <p>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.</p> <p>This concept is based on the author’s clinical observations and theoretical exploration of insulin timing, β-cell physiology, and metabolic regulation.<br>Dr. Aditya Bikram Mishra, MD (Medicine)<br>Senior Fellow in Diabetes (IDF)<br>Dibya Aditya Diabetes Care, Cuttack</p> <p>“Repaglinide does not increase insulin—it restores its timing.”<br>“Modern therapy floods insulin—Repaglinide whispers it at the right moment.”</p> <p>Keywords </p> <p>Repaglinide<br>Meglitinide<br>Temporal insulin alignment<br>β-cell preservation<br>First-phase insulin secretion<br>Postprandial hyperglycemia<br>Insulin timing physiology<br>Type 2 diabetes mellitus<br>Oral hypoglycemic failure<br>Endogenous insulin utilization<br>Secretagogue pharmacodynamics<br>β-cell stress and exhaustion<br>Neuroendocrine metabolic regulation</p> |
| title | Repaglinide Revisited: A Temporal Insulin Alignment Hypothesis for β-Cell Preservation and Metabolic Efficiency in Type 2 Diabetes Mellitus |
| url | https://doi.org/10.5281/zenodo.19158518 |