Salivary Function and Dental Changes During GLP-1 Therapy

Glucagon-like peptide-1 (GLP-1) receptor agonists, including semaglutide and tirzepatide, have become widely used for the treatment of obesity because of their substantial effects on body weight reduction and metabolic control. As the use of these medications continues to increase, attention has shifted toward their potential systemic and oral adverse effects. Recent clinical reports and pharmacovigilance studies have described oral complaints such as xerostomia, hyposalivation, oral discomfort, altered taste perception, and dental problems in individuals receiving GLP-1 receptor agonist therapy. However, the biological mechanisms underlying these observations remain largely unknown.

Saliva is essential for maintaining oral homeostasis. It provides lubrication, buffering capacity, antimicrobial protection, and contributes to the remineralization of dental hard tissues through its mineral content, particularly calcium and phosphate ions. Alterations in salivary secretion, pH, or mineral composition may impair the protective functions of saliva, thereby increasing the susceptibility to dental erosion, enamel demineralization, and other hard tissue alterations. Although reduced salivary flow has been described in isolated reports of semaglutide users, prospective clinical evidence evaluating changes in salivary composition during GLP-1 receptor agonist therapy is currently lacking.

Weight loss associated with GLP-1 receptor agonists may also indirectly influence oral health. Gastrointestinal adverse effects, particularly nausea and vomiting, as well as changes in dietary habits, fluid intake, and gastroesophageal reflux symptoms, may increase exposure of dental tissues to acidic conditions. Furthermore, dehydration resulting from reduced oral intake or gastrointestinal symptoms may contribute to impaired salivary function. These factors may act individually or synergistically to influence the integrity of dental hard tissues during treatment.

This prospective observational cohort study aims to evaluate changes in salivary calcium concentration, salivary flow rate, salivary pH, and dental hard tissues in adults initiating semaglutide or tirzepatide therapy for obesity. Participants will undergo standardized oral examinations, body weight measurements, intraoral photography, and unstimulated whole saliva collection before treatment initiation and after three months of therapy. Dental hard tissue changes will be assessed using the Basic Erosive Wear Examination (BEWE) index, while saliva samples will be analyzed for calcium concentration, pH, and salivary flow rate using standardized laboratory procedures.

The primary objective of this study is to determine whether treatment with GLP-1 receptor agonists is associated with changes in salivary calcium concentration during the first three months of therapy. Secondary objectives include evaluating changes in salivary pH, salivary flow rate, dental hard tissue status assessed by BEWE, body weight, and standardized photographic findings. In addition, the study will investigate the relationships between weight loss, gastrointestinal symptoms, salivary alterations, and dental hard tissue changes.

Because prospective studies evaluating the oral effects of GLP-1 receptor agonists remain limited, this study is expected to provide novel clinical evidence regarding the potential impact of these medications on salivary function and dental hard tissues. The findings may contribute to the early recognition of oral changes during obesity pharmacotherapy and support the development of preventive strategies through collaboration between endocrinologists and dental professionals.

Inclusion criteria

• Adults aged 18 years or older.
• Body mass index (BMI) ≥27 kg/m².
• Clinical decision by an endocrinologist to initiate semaglutide or tirzepatide therapy for obesity management.
• No previous treatment with GLP-1 receptor agonists.
• Willingness to participate and ability to provide written informed consent.
• Willingness to attend both the baseline and 3-month follow-up visits.

Exclusion criteria

• Previous use of any GLP-1 receptor agonist.
• History of head and neck radiotherapy.
• Sjögren syndrome or other systemic diseases affecting salivary gland function.
• Chronic kidney disease.
• Pregnancy or breastfeeding.
• Use of medications known to markedly affect salivary secretion.
• Active orthodontic treatment.
• Severe dental erosion requiring restorative treatment at baseline.
• Edentulism or the absence of anterior teeth required for dental hard tissue assessment.
• Inability or unwillingness to comply with the study protocol or attend the 3-month follow-up visit.
• History of eating disorders associated with recurrent self-induced vomiting (e.g., bulimia nervosa).
• Medical conditions causing persistent vomiting or severe gastroesophageal disease unrelated to GLP-1 therapy.