Lean (n = 10) and nondiabetic obese (n = 10) subjects received exenatide (a GLP-1 agonist) or saline infusion, and fMRI responses to visual stimuli (food and nonfood images) were recorded.
In general, patients using GLP-1-RA were younger (mean [SD], 49.6 [10.8] years vs 59.3 [10.9] years), had lower mean (SD) glycosylated hemoglobin levels (8.5% [1.2%] vs 9.6 [1.7%]), had lower mean (SD) fasting plasma glucose levels (9.0 [1.9] mmol/L vs 10.8 [2.6] mmol/L), higher mean (SD) body mass indexes (29.4 [3.9] kg/m<sup>2</sup> vs 24.6 [3.1] kg/m<sup>2</sup>), had higher comorbidity of obesity (75% vs 15%), had a higher occurrence of hyperlipidemia (63% vs 44%), and had lower occurrence of neuropathy (13% vs 34%) when compared with those using insulin (P < 0.0001 for all).
These studies suggest that compound 4d behaves well in lowering body weight and maintaining energy expenditure without a chance of hyperglycaemia, 4d has strong clinical potential as an efficient GLP-1/GCGR agonist in the prevention and treatment of obesity and dyslipidemia.
This finding provides evidence that sDPP4 and GLP-1 may play an important role in the pathogenesis of obesity, suggesting that sDPP4 may be valuable as an early marker for the augmented risk of obesity and insulin resistance.