When combined with GLP-1 therapies, these tools provide a comprehensive approach to managing both sleep and metabolic health
Within these pathways, phospholipase C (PLC) is speculated to play a critical role by potentially catalyzing the formation of second messengers, such as inositol triphosphate (IP3) and diacylglycerol (DAG)
Over time, excessive drinking slows down our metabolism across the board
Evidence references ADJUNCT ONE, PMID 27506222 ADJUNCT TWO, PMID 27493132 ADJUST T1D, PMID 40550013 Semaglutide crossover study, PMID 39794615 Tirzepatide observational data (Shah 2024), PMC11571402 Shah discontinuation post-hoc (ADJUNCT I/II), PMID 39717993 Shah 2025, GLP-1RA / tirzepatide in T1D with severe early (genetic) obesity ( JDST ) Insulin titration paper, PMID 39829697 Adjunct therapy review, PMID 40618954 Bone health review, PMC8118128 Weight loss and bone, PMID 38916894 Consensus and guidelines: ADA Standards 2025, PMID 39651989 ISPAD 2024, PMID 39657603 GLP-1 AID consensus, PMID 39517127 Related reading on GNL This Episode 17 conversation was the inspiration for the four-part Adjunctive Therapies guide built on top of the April 2026 evidence update
These analogs are administered orally or subcutaneously and are well-tolerated by patients
Impaired TCA cycle activity and reduced IDH3 exacerbate lactate accumulation, which increases lactylation and induces PAX6 expression, forming a positive feedback loop that promotes tau hyperphosphorylation, A accumulation, and synaptic dysfunction (Abdolmaleky et al., 2019
