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In trials that added it to injected insulin, basal insulin requirements fell roughly 60% to 80% while control improved. Low-blood-sugar risk therefore tracks the insulin or sulfonylurea used alongside tirzepatide more than the tirzepatide dose itself

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At low doses (125 g/kg), metformin activates AMPK, enhancing endothelial nitric oxide synthase (eNOS) activity, improving vascular function, and reducing myocardial injury (Zhou et al., 2001)