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The SUSTAIN-6 trial (Marso et al., New England Journal of Medicine, 2016) showed a 26% reduction in major adverse cardiovascular events (MACE) with subcutaneous semaglutide vs placebo in patients with type 2 diabetes and high cardiovascular risk
The high insulin levels could probably cause a downregulation of IGF-I production by the liver and other tissues, as a compensatory homeostatic mechanism, induced most likely through a differential modulation of IGFBPs production
Among many findings, GLP-1 use was associated with lower risk of Alzheimers disease and other neurological outcomes compared with usual care, with effect sizes varying by comparator drug class
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