Which GLP-1 Option Would You Choose for Obesity and Type 2 Diabetes?

No big winner emerged last year when Diana Isaacs and Jennifer N. Clements held their great debate session about the best glucagon-like peptide 1 (GLP-1) receptor agonist drug for maximizing glycemic control and weight loss in a patient with obesity and type 2 diabetes.

So Isaacs and Clements held a fresh debate this year during their Dec. 10 Midyear Clinical Meeting & Exhibition session, Let the Debate Begin: GLP-1 Receptor Agonists vs. Newer Incretin Mimetics for Obesity and Type 2 Diabetes.

Isaacs, an endocrine clinical pharmacy specialist at the Cleveland Clinic Diabetes Center in Ohio, was on team tirzepatide last year.

This year, Isaacs argued the merits of semaglutide while Clements, a clinical professor and director of pharmacy education at the University of South Carolina College of Pharmacy in Greenville, switched teams to make her case for tirzepatide.

Although the debate was good-natured, the national statistics around diabetes and obesity are sobering. The Centers for Disease Control and Prevention (CDC) estimates that more than 38 million Americans have diabetes, with type 2 diabetes accounting for at least 90% of cases. More than 20% of U.S. adults with diabetes don’t know they have the disease, according to CDC.

“The rates of type 2 diabetes are very, very high, and they are growing,” Isaacs said. “Of people with type 2 diabetes, 90% of them also have obesity. So really, these conditions are very linked with each other.”

Joe, the fictional patient for this year’s debate, is a 61-year-old white male whose medical history includes type 2 diabetes, obesity, hypertension, stage three chronic kidney disease, and sleep apnea. Joe is a nonsmoker who reports alcohol use (1–2 drinks daily) and a family history of both type 2 diabetes and obesity.

A major challenge for the debaters was the fact that a wealth of clinical studies demonstrate that semaglutide and tirzepatide are both extremely effective for glycemic and weight management. Isaacs and Clements reviewed definitive data on diabetes and weight loss from key studies, including the SURPASS and SURMOUNT trials (tirzepatide) and the STEP and SUSTAIN trials (semaglutide).

To make their debate points, both presenters focused on how Joe’s comorbid conditions and other clinical factors might be improved by taking a GLP-1 medication.

Clements said a 2022 report on data from the SURPASS-4 study found that tirzepatide slowed the estimated glomerular filtration rate decline and reduced the urine albumin-creatinine ratio in certain patients with diabetes. She said this kidney outcomes data could be meaningful for Joe, who has kidney disease.

“I do think it highlights the potential benefit of tirzepatide and is something we can look forward to with this medication,” Clements said.

Clements also noted that tirzepatide appears to be slightly more effective than semaglutide for weight loss. She said that could result in some benefit for patients with liver disease.

“With weight loss, that’s really the primary intervention we look at [in patients with] with liver disease. And tirzepatide ... has a powerful weight loss effect,” Clements said. “Joe may be at risk because he does drink, and also has type 2 diabetes which increases his [liver disease] risks, and we want to lower that.”

But Clements acknowledged one downside for tirzepatide; although some evidence exists that the drug has cardiovascular benefits, tirzepatide hasn’t yet been definitively shown to reduce major adverse cardiovascular events (MACE).

That’s not so for semaglutide, which has been shown in placebo-controlled clinical trials to greatly reduce MACE in people with diabetes and cardiovascular risk factors and in people with obesity and cardiovascular disease.

“Guidelines say to use agents with proven benefit in this [cardiovascular risk] population,” Isaacs emphasized. “Semaglutide has proven a benefit.”

That point seemed to help sway the session’s members, 59% of whom favored semaglutide over tirzepatide in an informal poll.

Isaacs said she hopes tirzepatide does prove to have great cardiovascular outcomes in clinical studies.

“But right now, it doesn’t; it hasn’t been published,” Isaacs said. “So do you want to choose an agent that maybe has a benefit, or do you want to choose something that has proven benefit now?”

Isaacs indicated that future debates about GLP-1 drugs could extend beyond semaglutide and tirzepatide, because several promising new drugs are under development.

“The future is really bright and really, really exciting in this space,” she said.