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The SUSTAIN-6 CVOT [67], performed in 3,297 patients with T2DM and ASCVD/CKD, has shown that compared to placebo, semaglutide was associated with increased retinopathy complications (3.0% versus 1.8%

It appears this may be most common in individuals with inflammatory bowel disease (IBD), such as Crohns disease

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Circulating plasma GLP-1 levels rise from approximately 510 pmol/L in the fasted state to 1550 pmol/L in the postprandial state, with peak levels depending on meal composition, caloric density, and rate of gastric emptying

Given that current PKA inhibitors broadly suppress all PKA activity, there is a clear need to develop novel, isoform-specific inhibitors that selectively target the C variants