Why do I feel hungry again? Is it still working?

Delayed gastric emptying is one of the initial effects that happens early on in taking Mounjaro or other GLP-1RA drugs. Whole part of what creates the feeling of fullness is the tirzepatide molecule ticking the GLP-1 receptors in the brain, this delayed gastric emptying also contributes greatly in the beginning. 


Delayed gastric emptying is a slowing of the emptying of the stomach contents into the intestines. It also is what some people attribute nausea to, indigestion, burping, and acid reflux. It eventually goes away, but the drug still works anyways.


“Although the GE effect showed near‐complete tachyphylaxis using the 5‐mg dose, the effect on postprandial glucose (self‐monitored blood glucose) was maintained following multiple 5‐mg doses. 5 It has also been shown that the impact of the 5‐mg dose on weight loss continues beyond 4 weeks (−4.8 kg at 26 weeks vs. −2.5 kg at 4 weeks). 6 This suggests that the attenuation of postprandial glycaemic rises, in the longer term, must be explained by other mechanisms over and above the waning effects on GE. 1 , 2 , 13 , 14 These results are aligned with a prior report by Jelsing et al.,4 who demonstrated the importance of GLP‐1‐mediated GE delay in the immediate (ie, acute) regulation of food intake or glucose control. However, GLP‐1’s effect on GE undergoes tachyphylaxis with chronic treatment but does not lead to a direct loss of glucose control or body weight effect, thereby demonstrating GLP‐1’s differential regulation of metabolism.


…In conclusion, these data suggest that the novel dual GIP and GLP‐1RA tirzepatide has similar effects on GE delay when compared with selective GLP‐1RA. GE delay is not the key driver for tirzepatide‐induced postprandial glycaemic efficacy and weight loss.”



The novel dual glucose‐dependent insulinotropic polypeptide and glucagon‐like peptide‐1 (GLP‐1) receptor agonist tirzepatide transiently delays gastric emptying similarly to selective long‐acting GLP‐1 receptor agonists

Diabetes Obesity Metabolism October 2020