GLP1 Medications for Weight Loss

Semaglutide (Wegovy) and dulaglutide (Trulicity) are in the news as medications that people can take to help lose weight. What are they, and how do they work?

Glucagon-like peptide-1 receptor agonists (GLP1) are drugs that were initially approved by the U.S. Food and Drug Administration (FDA) for the treatment of diabetes mellitus type 2 (DM2). They work by mimicking the body’s GLP-1 hormone produced in the small intestines of the gut, which affects other hormones and three organs key to how the body digests and regulates sugar. GLP1s work to treat DM2 by: 1) signaling the pancreas to produce insulin when needed; 2) decreasing the liver’s production of glucagon, a hormone that raises glucose; and 3) decreasing the rate the stomach absorbs food. Together, these actions improve DM2 through better sugar levels after eating and better sugar levels in the morning.

GLP1s can also help people lose weight by

• Affecting the hypothalamus in the brain to increase satiety, which can help you feel full after eating less and not as hungry as soon after eating.

• Slowing how quickly the gut absorbs food, which increases satiety.

• Regulating appetite and lower glucose.

• Increasing insulin production when needed.

Obesity is a major cause of DM2; hence, why one of the first recommendations doctors give after diagnosing a patient with DM2 is to lose 5-10% of your body weight. Early on, it became evident that GLP1 drugs helped DM2 by directly affecting sugar levels and indirectly triggering weight loss.

Common side effects include indigestion, nausea, and diarrhea. Eating smaller meals and more slowly can help decrease these side effects. Less common effects include bloating, belching, flatulence, recurrent fever, and stomach pains. Rarely there may be intestinal blockage, gastroparesis (stomach paralysis), or pancreatitis.

All GLP1s are by injection except for semaglutide in the form of a pill called Rybelsus. Semaglutide has two other injectable versions: Ozempic for DM2 and Wegovy for weight loss. The drug is the same just sold under different names with different dosing. The same is true for liraglutide: Victoza for DM2 and Saxenda for weight loss. There are other GLP1s, such as dulaglutide (Trulicity) and exenatide (Byetta and Bydureon). They are all effective for weight loss. Semaglutide seems to be the most effective.

Of note, there is one more GLP1 called tirzepatide, but it is a little different because it affects both GLP1 and glucose-dependent insulinotropic polypeptide (GIP) receptors. A recent study found tirzepatide to be the most effective GLP1 for weight loss, surpassing semaglutide. Anecdotally, it may have less side effects of nausea, vomiting, and diarrhea.

GLP1s are expensive, ranging from $800-$1,200 monthly. Be very careful of online sites that offer very discounted prices. Sometimes the low price is for the starting dose only, and most people need more than that for weight loss; sometimes the drug is compounded, which may result in consistency or efficacy issues; sometimes it is a bait and switch; sometimes the drug is fake. While not endorsing any of these sites, Henry and sites run by the manufacturers seem to be reputable. The prescription and care at these sites are through nurse practitioners not connected to your doctor, so you will need to inform your family physician if you decide to go that route. There are other sites, especially compounding sites, which may be trustworthy. It is imperative to do your homework.

As they have been used and studied more, GLP1s have been found to be beneficial for treating heart failure or chronic kidney disease in some patients. They can also reduce the risk of cardiovascular death, heart attack, and stroke in adults with cardiovascular disease and who are either obese or overweight. Other areas under study include potential in some people to decrease colon cancer risk or assist with cravings for substances like alcohol or cocaine.

Overall, GLP1s are considered generally safe and very effective treatments for obesity and DM2 with other benefits for heart failure, chronic kidney disease, and cardiovascular disease. Their benefits on health outcomes are due to weight loss, direct impact on the disease process, or some combination of the two.

It is best to work with your family doctor to see if one of these medicines is safe for you and could improve your health or health risks.

Dr. Stephen A. Wilson, MD, MPH, FAAFP, is Chair of Family Medicine at Boston University Chobanian and Avedisian School of Medicine and Chief of Family Medicine for Boston Medical Center.