doi: 10.1152/ajpcell.00153.2023 15
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More importantly, a large-scale 3b-phase randomized controlled trial (SURMOUNT-5), which compared semaglutide with tirzepatide in 751 obese adults without type 2 diabetes, explicitly reported that male patients had an average weight loss approximately 6 percentage points lower than female patients after 72 weeks of semaglutide treatment, further verifying that sex is an independent factor affecting semaglutides efficacy [80]
The side effects of GLP-1 RAs can include gastrointestinal symptoms such as nausea, vomiting, and diarrhea, which are usually transient but may affect patient adherence, as well as rarer complications that require careful monitoring in clinical practice

Through these molecular mechanisms, GLP-1 not only plays a crucial role in the treatment of diabetes by enhancing the function and protecting pancreatic -cells from apoptosis, but it may also offer potential therapeutic benefits in fields such as cardiovascular and neural protection.198,205,206 GLP-1 can also enhance the uptake and utilization of glucose in muscle and adipose tissues.207,208,209 And GLP-1s action in the brain reduces appetite and may influence energy expenditure.176,210,211 These effects involve interactions with other satiety and hunger signals, such as PYY, CCK, insulin, and leptin.212,213 GLP-1 PI3K/Akt - .1,188 GLP-1 .189,190,191 GLP-1R (AC) cAMP( ) .191,192 GLP-1R , GPCR Class I PI3Ks .1 PI3Ks SH2 PI3K PI3K .193 GPCR .194,195 PI3K -4,5-(PIP2) -3,4,5-(PIP3) .196 PIP3 Akt