As clinical laboratory testing sheds light on the effects of popular new drugs such as Ozempic and Wegovy, biomarker testing and tissue imaging are already revealing how the drugs change body composition.
Researchers at the University of Wisconsin in Madison looked deeper than weight and waist circumference to focus on certain biomarker measures related to cardiometabolic risk. Penning a multispecialty article this month, a team led by Dr. Leslie Nelson assessed tissue-level changes in body composition after initiation of glucagon-like peptide-1 (GLP-1) agonist treatment (semaglutide).
Semaglutide, better known by Ozempic and Wegovy (Novo Nordisk) and others, belongs to a newer class of medications known as GLP-1 receptor agonists (RA). Semaglutide is among several hormone-mimicking and/or antagonizing drugs cleared for marketing by the U.S. Food and Drug Administration (FDA) to treat type 2 diabetes, obesity, and, as of May 2024, to reduce risk of serious heart problems specifically in adults with obesity or overweight.
The University of Wisconsin Madison study combined radiology, medical physics, and laboratory findings to evaluate tissue changes in people on the drug, using a validated suite of explainable computed tomography (CT)-based artificial intelligence (AI) body composition tools and clinical laboratory data.
The study also considered clinical variables found through electronic medical record (EMR) reviews at the time of the pre- and post-semaglutide scans in each patient. These variables included weight, BMI, hemoglobinA1c (HbA1c), and C-reactive protein (CRP), according to Nelson and colleagues.
"Patients using semaglutide who lost versus gained weight demonstrated distinct patterns of changes in CT-based body composition measures," the team concluded. "Those with weight loss exhibited overall favorable shifts in measures related to cardiometabolic risk. Muscle attenuation decrease in those with weight gain is consistent with decreased muscle quality."
An assessment of laboratory markers of glycemic control and inflammation found that HbA1c was significantly lower on the post- than on the pre-semaglutide scan in the weight-loss group (7.3 vs. 8.5%, p = .02; n = 17). Otherwise, HbA1c and CRP were not significantly different between the pre- and post-semaglutide scans in any of the three groups, although CRP remains a useful marker for future analyses, the authors said.
The researchers noted that known indications for the pre-semaglutide scans were pain, cancer, urolithiasis, infection, vascular pathology, trauma, hernia, hematuria, bowel obstruction, abdominal distention, bleeding, cirrhosis, and nausea, constipation, pancreatitis, membranous nephropathy, renal cyst, or transplant evaluation.
Likewise, known indications for the post-semaglutide scans included the same as the pre-semaglutide scans but also included elevated liver function tests, adrenal adenoma, lymph node follow-up, and enlarged appendix.
Importantly, the tissue scans highlighted and measured visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), SAT and VAT attenuation, skeletal muscle cross-sectional area and muscle attenuation, as well as intermuscular adipose tissue. The study also measured liver and kidney volume (in milliliters [mL]) and attenuation (in Hounsfield units [HU]), in addition to abdominal aortic calcification with an Agatston score, and trabecular bone mineral density.
30-year-old woman with semaglutide use. Patient had stopped semaglutide use 36 days prior to post-semaglutide scan. Patient's weight was 148 kg on pre-semaglutide scan and 176 kg on post-semaglutide scan. Patient was thus assigned to weight-gain group. (A) Coronal maximum-intensity projection (MIP) image from pre-semaglutide scan shows organ segmentations. (B) Axial image from pre-semaglutide scan at L3 level shows color-coded tissue segmentations. (C) Coronal MIP image from post-semaglutide scan shows organ segmentations. (D) Axial image from post-semaglutide scan at L3 level shows color-coded tissue segmentations. Segmented visceral adipose tissue (VAT) is colored yellow, subcutaneous adipose tissue (SAT) is colored blue, skeletal muscle is colored red, liver is colored red, and spleen (not evaluated in present investigation) is colored orange. On pre- and post-semaglutide scans, VAT area was 358.5 cm2 and 412.1 cm2, muscle area was 186.8 cm2 and 225.2 cm2, muscle attenuation was -5.2 HU and -11.0 HU, liver volume was 2,579 and 3,851 mL, and liver attenuation was 77.8 HU and 59.2 HU, respectively. Images and caption courtesy of the American Journal of Roentgenology.
Semaglutide carries a boxed warning, formerly “black-box warning," of thyroid tumors and cancer, along with many other warnings and potential complications for the liver and kidneys among others.
“In earlier laboratory studies, researchers noticed an increased incidence of a specific type of thyroid cancer called medullary thyroid cancer [MTC]," stated Dr. Ryan McSpadden, in a September 5 alert from Roswell Park Comprehensive Cancer Center in Buffalo, NY.
MTC is a rarer form of thyroid cancer, and researchers have found no incidence to date of semaglutide causing any kind of thyroid cancer in humans, according to McSpadden, but the earliest laboratory research identifying a correlation between semaglutide and MTC was strong enough for the FDA to warrant a boxed warning.
“All of these drugs are the same drug but in different formulations and given in different dosages," McSpadden said. “Overall, the results have been mixed, with some trials saying that there’s no increased risk and some trials saying that there’s a slight increased risk. But there has been really no evidence to show that there is a substantial risk of non-medullary thyroid cancer associated with these weight loss drugs."
As use of GLP-1 drugs soars around the world, researchers in the medical community will develop innovative testing approaches for intrapatient analysis. The University of Wisconsin Madison study suggests that automated CT-based AI tools provide biomarkers of body composition changes in patients using semaglutide that are beyond that which is evident by standard clinical measures.
The findings add to current research regarding Ozempic's efficacy, according to Nelson's team. Read the full study in the American Journal of Roentgenology here.
