The connection between oral health and systemic disease is well established in adults — but what about children? A team of researchers at the University of Kentucky (UK) is taking on that question with an ambitious new study examining how pharmacological weight-loss therapy may also improve periodontal health in adolescents with extreme obesity.
The study, known as MODERN-Dental, will investigate whether semaglutide—a glucagon-like peptide-1 receptor agonist (GLP-1 RA) better known by brand names Ozempic and Wegovy—can reduce gingival and periodontal inflammation, alter the oral microbiome, and improve systemic markers of inflammation in youth. The project represents one of the first mechanistic studies to examine the oral effects of GLP-1 therapy in pediatric populations and could pave the way for more integrated models of dental and medical care.
Leading the MODERN-Dental project is Oelisoa Andriankaja, D.D.S., Ph.D., associate professor at the UK College of Dentistry. The initiative builds upon the ongoing MODERN Trial (Mitigation of Cardiovascular Disease Risks in Children with Extreme Obesity), led by John Bauer, M.D., in the UK Department of Pediatrics.
To support this innovative work, Andriankaja recently received a Breakthrough Ideas Grant (BIG)—$125,000 per year for three years—funded by the Barnstable Brown Diabetes and Obesity Center and The Bill Gatton Foundation. The BIG program provides “support for rapid translation of dramatic breakthroughs from the laboratory to patients from Kentucky and beyond,” making it an ideal fit for MODERN-Dental’s goals. The study also receives support from the EXCEL program and the Department of Pediatrics through mentorship and resources.
“We know that obesity affects every organ system,” said Andriankaja. “What remains underexplored is how improving metabolic health through medications like semaglutide may also improve oral health. Our goal is to understand those mechanisms and identify early, noninvasive biomarkers of systemic health through the mouth.”
Obesity in children, as in adults, drives chronic low-grade inflammation that can influence multiple body systems—including the oral cavity. Adipose tissue releases pro-inflammatory cytokines and adipokines that alter immune responses and endothelial function, setting the stage for both metabolic dysfunction and periodontal breakdown. While adult studies have linked obesity and periodontitis through shared inflammatory pathways, little is known about how these processes operate in pediatric patients.
“We often think of gum disease as an adult issue,” said Luciana Shaddox, D.D.S., M.S., Ph.D., a periodontist and co-investigator on the study. “But gingival inflammation is extremely common in children, especially those with obesity. Understanding how systemic therapies impact the developing immune system and oral microbiome could transform how we approach prevention.”
The MODERN-Dental study will enroll 50 adolescents ages 12 to 18 who are already participating in the parent MODERN trial. Participants will undergo oral examinations and biospecimen collection at baseline, six months, and twelve months while receiving standard semaglutide treatment for obesity. Researchers will measure periodontal status—including plaque index, gingival index, probing pocket depth, and bleeding on probing—and analyze local and systemic biomarkers of inflammation and endothelial function in saliva, gingival crevicular fluid, and serum. They will also study changes in the oral microbiome using 16S rRNA sequencing of plaque samples.
Half of the participants will also receive professional dental cleanings at baseline, six, and 12 months, allowing the team to evaluate whether adjunctive oral care amplifies the systemic and periodontal benefits of semaglutide treatment. All oral assessments and procedures will take place at the UK College of Dentistry Wellness Center, under the supervision of Debora Scheffel, D.D.S., Ph.D., pediatric dentist, and Shaddox.
“For many children, dental visits are their most consistent point of contact with healthcare,” said Scheffel. “By integrating preventive dental care into obesity treatment, we’re creating a model of comprehensive, coordinated health for at-risk youth.”
Kentucky consistently ranks among the top states for both childhood obesity and dental disease. Nearly one in four adolescents in the Commonwealth is classified as obese, and rates of dental decay and gingivitis exceed national averages—especially in rural and low-resource communities.
“Children in Kentucky are disproportionately affected by conditions that are largely preventable,” said Bauer. “By understanding how oral health intersects with metabolic health, we can deliver more effective interventions and potentially reduce long-term disease risk.”
The MODERN-Dental team hopes the project will identify salivary and gingival biomarkers that could serve as early indicators of systemic metabolic improvement. Such findings could lead to the development of noninvasive screening tools and justify expanded coverage for preventive dental care under Medicaid and other public health programs.
While the study is designed as a pilot, it will generate essential preliminary data for future NIH applications, including a potential R01 or UG/UH3 grant focused on oral-systemic mechanisms in youth. By analyzing how semaglutide-induced metabolic changes influence oral inflammation and microbiome profiles, the team aims to uncover previously unrecognized pathways linking periodontal and metabolic health.
“Our findings could redefine how we think about the relationship between obesity and oral disease,” said Andriankaja. “Ultimately, this is about improving overall health outcomes—starting with the next generation.”
The MODERN-Dental project brings together experts from across the University of Kentucky, including dentistry, pediatrics, pharmacology, nutrition, and epidemiology. Alongside Andriankaja and Bauer, key investigators include Hong Huang, Ph.D., Department of Pediatrics; Barbara Nikolajczyk, Ph.D., Department of Pharmacology and Nutritional Sciences; Luciana Shaddox, D.D.S., M.S., Ph.D., Center for Oral Health Research; Gregory Hawk, Ph.D., Department of Biostatistics; Debora Scheffel, D.D.S., Ph.D., Pediatric Dentistry; and Dawn Dawson, Ph.D., Center for Oral Health Research.
As medications like semaglutide become more common in pediatric obesity care, understanding their broader health effects will be increasingly important. MODERN-Dental stands at the forefront of this conversation, uniting medical and dental researchers in pursuit of a more holistic approach to child health.
“This is the kind of project that moves the field forward,” said Andriankaja. “It challenges us to think beyond traditional boundaries—and reminds us that oral health is a window into overall health.”