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It did not take long, however, for the first major controversy regarding SUs to emerge, when tolbutamide was deemed to have caused an excess of cardiac deaths by the University Group Diabetes Program (UGDP), leading to the premature termination of this limb of its multicenter, placebo-controlled clinical trial [16]

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The application of autophagy-related molecules as therapeutic targets to counteract DOR is still in its early stages and warrants additional research to clarify both their therapeutic potential and associated risks

NO, nitric oxide

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