Doctor explains key differences between GLP-1s, GLP-2s and GLP-3s

GLP-1 medications like Ozempic, Wegovy, Mounjaro and Zepbound have dominated conversations around weight loss and diabetes management for the last few years, and now people online have started asking about other versions, including GLP-2 and GLP-3.

But according to doctors, one of those doesn't actually exist as an official medication class at all.

Andrew Kraftson, M.D., clinical associate professor of internal medicine and clinical director of the Post Bariatric Endocrinology Clinic and Weight Navigation Program at the University of Michigan, and Absalon Gutierrez, M.D., an endocrinologist at UTHealth Houston, have explained the real differences between the hormones, and cleared up exactly what people mean when they say GLP-3.

Dr. Kraftson said GLP-1 is a hormone made by cells in the intestine that is activated by food, helping the body process energy and signaling to the brain and gut when a person is full.

Dr. Gutierrez explained that GLP-2 is also produced by intestinal cells, but serves a completely different purpose, as it 'regulates intestinal growth, structural integrity and nutrient absorption.'

The only FDA-approved synthetic GLP-2 medication is Gattex, known generically as teduglutide, which treats short bowel syndrome.

GLP-1 and GLP-2 are both hormones produced in the gut, according to Andrew Kraftson, M.D., clinical associate professor of internal medicine and clinical director of the Post Bariatric Endocrinology Clinic and Weight Navigation Program at the University of Michigan. (Photo by Peter Dazeley/Getty Images)

What is GLP-3 and does it help with weight loss?

As for GLP-3 Dr. Gutierrez said the term is sometimes used inaccurately to describe triple hormone receptor agonists, which combine GLP-1, glucagon and glucose-dependent insulinotropic polypeptide (GIP).

In reality, there is no official GLP-3 hormone or medication class.

People are likely referring to retatrutide, a triple hormone receptor agonist currently in development by Eli Lilly and undergoing clinical trials.

Retatrutide is still investigational, has not been approved by the FDA, and its full safety profile has not yet been established, meaning it does not affect weight loss in any confirmed, clinically approved way, unlike GLP-1 drugs.

Dr. Kraftson said GLP-1 stimulates the pancreas to boost insulin, lowers blood sugar, signals fullness to the brain and slows digestion, adding that 'collectively, these actions can help keep sugars and weight under healthy control.' GLP-2, meanwhile, isn't currently known to support weight management at all, and instead focuses on repairing the intestinal lining and helping the body absorb nutrients.

GLP-1 stimulates the pancreas to boost insulin and lower blood sugar by processing it, signaling to the brain when you’re full and slowing digestion.(Photo by: Michael Siluk/UCG/Universal Images Group via Getty Images)

Can you take GLP-1 and GLP-2 medications together?

Dr. Gutierrez said there is 'no additional weight loss benefit from combining GLP-1 and GLP-2, since the two hormones, despite both originating in the gut, are prescribed to treat entirely separate conditions.

Both hormone types come with their own side effects.

GLP-1 drugs can cause nausea, diarrhea, vomiting, constipation, fatigue and hair loss, according to Dr. Kraftson, along with rarer but more serious risks like pancreatitis, dehydration, vision changes in people with type 2 diabetes and possible thyroid tumors.

GLP-2 medications carry similar risks, including abdominal pain, nausea and swelling of the hands or feet, alongside more severe potential complications such as abnormal cell growth, intestinal polyps and bowel blockages.

UNILAD has contacted Eli Lilly for comment.