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Several studies revealed that GLP-1RAs relieve myocardial damage and glucose toxicity by promoting autophagy, which is associated with decreasing mTOR phosphorylation and increasing AMPK phosphorylation [88]

Analysis of fractures in patients with type 2 diabetes treated with empagliflozin in pooled data from placebo-controlled trials and a head-to-head study versus glimepiride

Intranasal insulin treatment also prevented the decline in cerebral glucose metabolism [160]

However, the renal beneficial effect of SGLT2-i has been definitely reported in recent cardiovascular outcome clinical trials and further confirmed in CREDENCE, DAPA-CKD, EMPA-KIDNEY, which investigated renal outcomes as primary endpoints also in non-diabetic patients with chronic kidney disease (48)

Recruitment has also begun for PIONEER 12, which is projected to be completed in August of 2021

GLP-1RAs exert pleiotropic effects that extend well beyond their initial use in glycemic management [8]