GLP-1s Aren't Magic: Keeping the Weight Off and the Muscle On

GLP-1s are everywhere right now, and for good reason. In this follow-up to the Peptides 101 episode, Kim Abrego calls them game changers in the weight loss space, but she's just as clear about what they can't do on their own.

GLP stands for glucagon-like peptide, and the medications behind the familiar names, Wegovy and Ozempic among them, work primarily by signaling fullness. You simply don't want to eat as much. Kim shares that some women tell her they're glad their husbands aren't on one, because they would forget to feed their children. The food noise just goes quiet. Most of these medications are injected once or twice a week, depending on how a physician prescribes them.

Kim walks through the three GLP-1s people talk about most. Semaglutide has a single signaling component, the GLP-1 fullness signal. Tirzepatide adds a second gut signaling peptide, GIP, which Kim says has helped reduce the nausea that caused many people to stop semaglutide, so they can stay on it longer and lose more weight. Retatrutide, not yet FDA approved and currently accessed on the gray market, adds glucagon, which she says raises energy and helps the liver burn more fat. In the studies Kim references, average weight loss rose from 13.7% with semaglutide and 20.2% with Tirzepatide over 72 weeks, to 28.3% with retatrutide over 80 weeks, about 70 pounds, a result Eli Lilly described as a level of loss long associated with bariatric surgery.

But the most important part of the conversation is behavior. A GLP-1 changes how much you eat, not necessarily what you eat. Stop the medication without building new habits, and research shows the weight tends to come back. “Why?” Kim asks. “Because it's not magic.” Her two critical behaviors are resistance training and protein, and she argues both should be in place before someone starts a GLP-1, so the medication supports the habits instead of standing in for them.

Resistance training matters because some of the weight lost on any weight loss program can come from muscle unless you actively protect it. In the studies Kim mentions, people who added resistance training and high-protein meals maintained, or even gained, lean muscle mass. That's the goal: weight loss that comes from fat, not muscle, and a body that stays strong enough to step up a curb in your 80s. Movement can start with whatever you enjoy, whether that's pickleball or yoga, but resistance training is the priority for anyone on a GLP-1. For those intimidated by the gym, Kim suggests circuit-style weight machines like the ones at Planet Fitness, a couple of dumbbells at home, or the Endura Exercise app, an eight-week foundations program that shows the equipment and muscles for each exercise.

Protein is the other half, and the hard part, since a GLP-1 makes eating feel like a chore. Kim's solution is liquid protein: shakes, or clear proteins that are easier to sip throughout the day. The target is one gram of protein per pound of target body weight, so someone at 200 pounds aiming for 150 would eat 150 grams.

For Kim, GLP-1s fit naturally within the Endura Method as a tool that supports the behavior change behind the Lift pillar: feeling strong, feeling powerful, and getting where you want to go, with habits that last long after the medication does.