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"Update on FDA's ongoing evaluation of reports of suicidal thoughts or actions in patients taking a certain type of medicines approved for type 2 diabetes and obesity"

doi: 10.1016/j.cmet.2016.08.020

Mechanisms underlying the rapid degradation and elimination of the incretin hormones GLP-1 and GIP

Palmer SC, Tendal B, Mustafa RA et al (2021) Sodiumglucose cotransporter protein-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists for type 2 diabetes: systematic review and network meta-analysis of randomised controlled trials

Dual GIP/GLP-1 agonists add GIP receptor activation, which: Amplifies insulin secretion beyond what GLP-1 alone achieves Increases insulin sensitivity in peripheral tissues Appears to shift adipocyte metabolism toward fat oxidation (mechanism still under investigation) May reduce the nausea signal that limits GLP-1 dose escalation (GIP has anti-emetic properties in animal models) The weight loss ceiling for tirzepatide is approximately 20% to 22% of baseline body weight at the 15 mg dose over 72 weeks (SURMOUNT-1 data)