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In 2022, updated Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guidelines recommended SGLT2i as first-line therapy for patients with estimated glomerular filtration rate (eGFR) 20 mL/min/1.73 m 2 (previously 30 mL/min/1.73 m 2 ) and GLP-1 RA as an additional therapy option for patients with insufficient glycemic control as part of a comprehensive risk-reduction approach for people with type 2 diabetes and CKD [5, 6, 14]

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This single structural quirk has an outsized functional consequence: it renders the molecule resistant to cleavage by standard cellular peptidases, which recognize alpha bonds