GLP-1s and Vanishing Muscle Mass

GLP-1 drugs for weight loss have become popular because they’re very effective. But there are some significant risks that may not be readily apparent to patients — most notably the potential for muscle loss. 

GLP-1s helps regulate blood sugar levels, appetite and satiety. This class of drugs enhances insulin secretion, suppresses glucagon release, slows gastric emptying, promoting feelings of fullness within the body. The combination leads to reduced caloric intake and subsequent weight loss.  

But those taking GLP-1s aren’t just losing fat. As highlighted in a recent Lancet commentary, they’re losing muscle at a rate far greater than those who restrict their calories without drug intervention. Muscle helps regulate metabolism, protect from infectious diseases, and trauma; losing too much of it can be damaging.  

Patients often stop and start GLP-1s – sometimes because they have trouble tolerating the drugs and other times because of issues accessing the medications. There’s a danger when they stop taking the drugs: there’s often rapid weight gain, much of it in the form of fat instead of muscle.  

In other words, patients lose a disproportionate amount of muscle when they’re on the drug, and they gain back a disproportionate amount of fat when they stop taking the drug. Replacing muscle with fat can lead to a series of undesirable health outcomes.  

To be sure, many of those taking GLP-1s are gaining significant advantages. For those who are obese and can stay on the drugs — or lose weight and keep it off – there is a reduced risk of heart disease and diabetes.  

Endevica Bio is researching an alternative approach that may not cause the same undesirable side effects as the GLP-1s. We are developing a peptide targeting obesity called 710GO that leverages the melanocortin system to induce weight loss. From the monkey studies we’ve done, 710GO resulted in the retention of a greater percentage of muscle mass compared to GLP-1s, with equivalent overall weight loss. 

We designed our peptide to mimic a thermostat where you can control the amount of weight loss to weight gain. In recent research, 710GO, led to a loss of 7 ½ percent of body weight in obese monkeys in one month relative to a control group. The study also showed a steady 20 percent decrease, on average, of daily caloric intake. There were no signs of nausea or any other gastrointestinal distress while on the drug. 

With more than three quarters of Americans being considered overweight or obese, there is a significant need for treatment options. Our peptide is showing great potential, and we are excited about the prospect of bringing another option to the market.  

By Dr. Daniel Marks, MD, PhD is Chief Medical and Scientific Officer at Endevica Bio.