UH Harrington Heart & Vascular Institute Preventive Cardiologist Leading Studies and Guidelines on Implementation of GLP-1s

Innovations in Cardiovascular Medicine & Surgery | June 2024

Ian Neeland, MD,FAHA, FACC

The wildly popular glucagon-like peptide (GLP-1) agonists for weight loss, such as semaglutide, liraglutide and tirzepatide, require doubling down on scientific expertise to better understand their effects and implications. That’s the view of University Hospitals (UH) Harrington Heart & Vascular Institute’s Ian Neeland, MD, FAHA, FACC, Director of the Center for Cardiovascular Prevention and Director of the Center for Integrated and Novel Approaches in Vascular-Metabolic Disease (CINEMA). Dr. Neeland is making important contributions in this regard. He’s conducting novel studies into these medicines and helping guide the clinical recommendations for heart and vascular specialists who want to offer them to their patients.

Dr. Neeland is Vice Chair of the American Heart Association’s guideline writing committee on implementing obesity science into clinical practice, which recently published its scientific statement in the journal Circulation.

“FDA approval and insurance coverage of the latest treatments, including GLP-1 medications, are integral to improving access to care and outcomes for people who need these therapies the most,” he says. “This is especially true for high-risk, high-need patients for the prevention of adverse cardiovascular events. It is encouraging that these steps in increasing access may lead to reduced risk of cardiovascular disease and improved outcomes for potentially millions of adults in the U.S.”

Dr. Neeland is also doing crucial research into the effects of GLP-1s on muscle composition. Although some have feared that these medications would adversely affect muscle composition, putting older patients at risk of sarcopenia and falls, that’s not what his research is showing, he says.

“These medications may actually improve muscle composition, because even though you might lose muscle mass with weight loss, the fat and the quality of the muscle may improve with the medication,” he says.

He recently led a randomized clinical trial showing that although there was a small reduction in thigh muscle volume with these medications, there was a significant reduction in muscle fat and some mild improvement in muscle quality. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow-up with liraglutide, but there was no change with placebo.

“In a cohort of predominantly women with overweight or obesity in the absence of diabetes, once-daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo,” he and his team wrote in the Journal of Cachexia, Sarcopenia and Muscle.

“This suggests that the changes in muscle with weight loss from these medications are adaptive similar to what you would see with weight loss of any other type,” Dr. Neeland says. “But also, people can improve muscle quality, which may actually improve muscle function, reducing risk for falls and improving one's mobility and function.”

Dr. Neeland has also conducted research into how the GLP-1 agonist tirzepatide affects body fat distribution patterns in people with type 2 diabetes – using a tool called a Z score.

“The Z score essentially tries to normalize change in muscle to what's expected versus what's unexpected with weight change,” he says. “If a Z score goes up or down, it means it's more or less than expected.”

Results from 296 patients, published in the journal Diabetes, Obesity and Metabolism, compared with a virtual control group, showed significant reductions in average visceral adipose tissue (VAT) and liver fat (LF), while abdominal subcutaneous adipose tissue (aSAT) increased from an initially negative value.

“There was a greater reduction in visceral fat and liver fat with the drug than you would have seen otherwise without it,” Dr. Neeland explains. “This suggests a possible treatment-related shift towards a more balanced fat distribution pattern with prominent VAT and LF loss.”

Dr. Neeland is next planning a “mechanistic” clinical trial to better understand the effects of GLP-1s on muscle in a more “profound” way, using molecular techniques and advanced imaging.

“We need to learn more about what potentially we can do to prevent muscle loss and improve muscle function during weight loss with these medicines, such as physical activity and exercise, weight training and specific protein supplementation,” he says. “Those type of things may counterbalance or counteract the effects to keep muscle healthy while people are losing a lot of weight with these medications.”