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However, anecdotal reports from online forums cited in a 2025 systematic review included anxiety and panic attacks, depression and anhedonia, insomnia, heart palpitations, fatigue and weakness, and loss of appetite
Mechanistic studies suggest that the potential direct cardiovascular benefits of SGLT2i include augmentation of signal transducer and activator of transcription 3 (STAT3), inhibition of sodium hydrogen exchange (sodium-hydrogen antiporter 1 [NHE-1]), improved mitochondrial metabolism, modulation of natriuretic peptides, improved vascular stiffness and autonomic tone, reduction of inflammation, and improved cardiac energetics
Semaglutide follows a gradual titration schedule designed to improve tolerance
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