Does it feel like your weight loss medication has quit working?

I’ve heard this from several of my patients who have been on either semaglutide, tirzepatide, phentermine, or Contrave for several months to years. They start the medication, have amazing weight loss, and then after several months, they don’t notice the effectiveness they once had. I have had a handful of patients who have had NO weight loss at all from either semaglutide or tirzepatide. NONE. Then there are the majority who continue to do well and still experience the benefits of weight loss and maintenance.

Sometimes, this lessened response or kind of habituation to a drug — a phenomenon called tachyphylaxis, can be easily solved if I up my patients' dose. In some cases, patients have already maxed out their dose and upping their prescription or changing to a stronger drug does not undo the plateau (tirzepatide is stronger as it impacts two hormones and semaglutide impacts one). Here, from what I have read, biology and pharmacy have hit their limits for reasons we still don't quite understand.

My exhaustive reading on this issue leads me to hypothesize why they don’t work in a small percentage of my patients. In many cases, medications attach to a protein called a receptor to create their effects. Tachyphylaxis can happen when receptors don’t react to a medication in the intended way. In some cases, the receptors become less sensitive to the medication. In other cases, the number of receptors decreases. This means there’s less places for medications to attach to in the body to create their effects.

Genetics can also play a role in tachyphylaxis. There are slight differences in how each person reacts to and breaks down medications. But these unique differences can sometimes lead to tachyphylaxis. This means some people may be at higher risk for developing tachyphylaxis to a medication than others.

Experts also suggest that it could be that a person's baseline emptying of food is so delayed that you're not going to get an incremental delay from this medication, or the brain has more than one satiety center, and perhaps the specific satiety center in the brain that these drugs work on in a particular person may not be super sensitive.

The good news is:

1. These drugs are going to get better and better. Eli Lilly is working on retatrutide that stimulates GLP-1, GIP and a third hormone known as glucagon.
2. You and I will work on behaviors and problem-solve ways to achieve weight loss without depending on medication completely. We can meet as often as you need for accountability. This is a lifestyle I want you to sustain!

Weight loss medication, like bariatric surgery, is a tool to help make behavioral skills easier to practice.

I hope this helps!
-Kate