GIP-induced inhibition of centrally mediated emesis signals triggered by GLP-1 administration enhances weight loss seen with GLP-1 RA administration.165 Unlike GLP-1, GIP by itself does not retard gastric emptying.166 Tirzepatide The GLP-1/GIP co-agonist, tirzepatide, has shown efficacy for both management of diabetes mellitus and weight loss.167 The SURMOUNT-1 trial found mean 72-week weight loss up to 20.9% at 15 mg weekly compared to 3.1% with placebo.67 Similar results were seen in the 5 SURPASS trials.76,168171 Tirzepatide was approved by the FDA for weight loss in 2022.172,173 Significant benefits for obesity-associated diseases are also being reported (Table 5) including reduced heart failure events at 104 weeks of follow up (hazard ratio [HR] 0.62 compared to placebo),110 improved management of obstructive sleep apnea at 52 weeks,111 and improved management of metabolic-dysfunction associated steatohepatitis (MASH) with a decrease of 1 fibrosis stage with no worsening of MASH at 52 weeks.107 Side effects of tirzepatide are similar to those of the GLP-1 receptor agonists.169,172,173 Real-World Impacts Although weight loss is significant in clinical trials of these medications, real-world evidence has shown significant variability in weight loss.174 Given high costs of these medications, discontinuation rates are as high as 50%, resulting in most real-world studies showing weight loss lower than clinical trials.174 Desire for these medications led to high levels of compounded formulations, potentially representing increased safety events reported in adverse events reported in Europe.175 AOMs Under Investigation With advances in understanding of the incretin system, there has been substantial development of new agents for obesity
however, the bodys micronutrient needs do not change, and, in fact, protein needs increase to support the rapid weight loss that occurs
European heart journal
L., & Brown, J
Exosomal MicroRNA-181a derived from mesenchymal stem cells improves gut microbiota composition, barrier function, and inflammatory status in an experimental colitis model
2024 Jul 17;10(1):77
