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The current understanding points to a potential biphasic pattern in GLP-1 RA studies, where any observed early worsening may be related to rapid glycemic improvement rather than direct retinal toxicity, particularly in patients with pre-existing retinopathy, poor glycemic control, and those undergoing HbA1c reduction 47

With more than 100 active GLP-1 clinical programmes worldwide, the bar for differentiation is rising rapidly

Instead of adding amino acids, DES removes the first three from the N-terminus, creating a truncated 67 amino acid peptide

doi: 10.1038/s41574-025-01114-y 139

While there are still many questions about TCF7L2 left unanswered, it has been shown that TCF7L2 is essential to the production of proglucagon via the intestinal cells (not the glucagon produced in the alpha cells of the pancreas).[ref] Genetic variants in TCF7L2 are associated with impaired glucose stimulation of insulin secretion and GLP-1.[ref] GLP1R (glucagon-like peptide 1 receptor) receives the signal from GLP-1, and variants in GLP1R have associations with altered BMI, weight, and insulin resistance

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