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Choosing between them depends on primary goals: metabolic optimization favors MOTS-c, while direct mitochondrial repair favors SS-31

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GLP-1 receptor agonists bind to and stimulate GLP-1 receptors, which augments insulin secretion and inhibits glucagon release by the pancreas in a glucose dependent manner, leading to reductions in plasma glucose.3334 This drug class also promotes satiety by delaying gastric emptying and acting on appetite regions of the hypothalamus, resulting in decreased food intake and sustained weight loss.33 Furthermore, GLP-1 receptor agonists may impart additional cardiovascular benefits by alleviating atherosclerosis through improving inflammatory markers.35 The anti-inflammatory and anti-oxidative effects of GLP-1 receptor agonists may also result in decreased albuminuria, reduced mesangial expansion, and improved glomerular hyperfiltration and endothelial function, explaining their renoprotective effects.3637 SGLT-2 inhibitors, on the other hand, exert their antihyperglycemic effects by inhibiting the reabsorption of glucose in the proximal tubules of the kidneys, resulting in urinary glucose excretion.38 The excretion of calories in the form of glucose in the urine also promotes weight loss.39 An interesting finding from our study was that adding an SGLT-2 inhibitor to existing GLP-1 receptor agonist treatment was associated with a decreased risk of heart failure, but this was not seen when GLP-1 receptor agonists were added to a background of SGLT-2 inhibitors

Antibody staining was visualized using Alexa Fluor-conjugated secondary antibodies (Invitrogen)