GLP-1 basics

Semaglutide and Tirzepatide

GLP-1 receptor agonists mimic a natural hormone in your body that is produced by the L-cells of the colon. They works naturally to increase insulin, to lower blood glucose, and lower glucagon, a hormone that also raises blood glucose. They slow gastric emptying to increase fullness after meals. They also reduce appetite due to dopamine signaling. This is why GLP-1s are effective for treating a myriad of addictive behaviors, they reduce the “pushing of the dopamine button” and can work for all addictions.

GLP-1 and GIP (Tirzepatide) has the additional benefit of amplifying the metabolic activity, namely insulin potentiation. GIP enhances beta cell insulin release (only when glucose is elevated). GIP enhances appetite suppression when GLP-1 is active.

Studies are somewhat mixed but most recently we are seeing better outcomes with weight reduction, visceral fat reduction and improved metabolic flexibility with tirzepatide.

The myth on muscle loss:

Research shows that semaglutide “improves mitochondrial efficiency in skeletal muscle” which is why muscle tissue gets stronger, both due to mitochondrial benefit and improved glucose transport into the muscle cells. Patients might lose muscle if they aren’t strength training, or if they lose a significant amount of weight, but the benefit to their overall health in the latter situation is enormous, especially if we are turning around their insulin resistance markers, and reducing body wide inflammation. Loss of muscle is not the fault of the GLP-1. In my experience, people will make better lifestyle choices once they have lost that weight, and feel better exercising (less weight to carry, less knee pain, more energy).

I use the attached pdf of GLP-1 benefits as a patient handout, they are often surprised to see the long list of health benefits. See next lesson on Indications for pdf.

Bone health and strength training:

It is crucial to encourage patients to do weight bearing or strength training exercise when taking a GLP-1 to reduce the risk of bone loss. The research on BMD is evolving but at this point (2026) some are showing modest declines in BMD when patients are taking a GLP-1. The people most prone to bone loss are post menopausal women not on hormone replacement therapy who are not doing weight bearing exercise.

Alternatively, some studies show improved bone mineral density due to increased osteoblast activity, decreased osteoclast activity and improved oxygen carrying capacity to the bone. They have even shown reduced fracture risk on GLP-1s.

The key here is making sure your patients are getting enough minerals, eating enough food (too high of a dose won’t allow them to meet caloric intake goals) and ensuring weight bearing activity.