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Clinical evidence suggests that tolerance to GLP-1 glucose-lowering effects does not develop in humans, despite occurring in animal models

Effect of exenatide on 24-hour blood glucose profile compared with placebo in patients with type 2 diabetes: a randomized, double-blind, two-arm, parallel-group, placebo-controlled, 2-week study

Mechanistically, GLP-1R activation raises cAMP levels and triggers the PKA/CREB (cAMP-response element-binding protein) signal transduction pathway, which regulates various cellular processes [111]

The primary concern relates to inadvertent pregnancy exposure rather than reduced conception rates

GLP-1 may act on bone by promoting bone formation, inhibiting bone resorption, and affecting the coordination of the two processes

In addition, the results of the ELIXA study answered the question of cardiovascular safety related to heart failure by displaying no significant between-group differences in the rate of hospitalization for heart failure (HR, 0.96