GLP-1 receptor agonist

A class of injectable medicines that mimic the gut hormone GLP-1, slowing gastric emptying and reducing appetite signaling, with the largest outcome trial base in modern metabolic medicine.

What the class does

GLP-1 is a hormone released by the gut after eating. It increases insulin release when glucose is high, suppresses glucagon, slows how quickly the stomach empties, and signals fullness in the hypothalamus. A GLP-1 receptor agonist is a modified version of that hormone, engineered to last days instead of minutes.

That combination is why the class changes eating behavior rather than metabolic rate. Food leaves the stomach more slowly, hunger signaling is quieter, and the effort of eating less drops sharply for most people.

Single and dual agonists are different molecules

Semaglutide acts at the GLP-1 receptor alone. Tirzepatide acts at both the GLP-1 and the GIP receptor, and the addition of GIP activity appears to matter. In SURMOUNT-5, a head to head randomized trial, tirzepatide produced greater weight loss than semaglutide over 72 weeks.

In their own pivotal trials, tirzepatide reported average weight reductions of roughly 15 to 21 percent across dose arms in SURMOUNT-1, and semaglutide roughly 15 percent in STEP 1, both against placebo groups losing 2 to 3 percent.

Beyond weight

The SELECT trial found that semaglutide reduced major adverse cardiovascular events in people with overweight or obesity and established cardiovascular disease who did not have diabetes. That is an outcome result, not a surrogate marker, and it is the strongest single piece of evidence the class has.

Side effects are dominated by gastrointestinal symptoms, mostly early and dose related. Loss of lean mass alongside fat mass is a real consideration, which is why protein intake, resistance training and body composition tracking belong in any serious program rather than the drug alone.

Baseline runs physician-guided GLP-1 programs using compounded tirzepatide and semaglutide, at standard and microdose levels. Speak with a Baseline consultant first; an independent licensed provider reviews your history, your goals and any lab work you choose to share, and decides what is appropriate.

References

  1. Drucker DJ. Mechanisms of action and therapeutic application of glucagon-like peptide-1. Cell Metab. 2018.
  2. Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1). N Engl J Med. 2022.
  3. Wilding JPH, et al. Once-weekly semaglutide in adults with overweight or obesity (STEP 1). N Engl J Med. 2021.
  4. Aronne LJ, et al. Tirzepatide versus semaglutide for the treatment of obesity (SURMOUNT-5). N Engl J Med. 2025.
  5. Lincoff AM, et al. Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT). N Engl J Med. 2023.