Oral adverse effects move into focus as incretin use expands
GLP-1 receptor agonists and dual GLP-1/GIP receptor agonists have become central therapies for type 2 diabetes and obesity because they improve glycaemic control, support weight loss, and reduce cardiovascular risk. Their rapid uptake has also created a new clinical question at the bedside: what happens to the mouth when incretin-based treatment becomes long term and widespread?
This protocol sets out a scoping review designed to map reported oral complications associated with GLP-1 receptor agonists and GLP-1/GIP dual receptor agonists. The review is being planned because emerging pharmacovigilance signals point to xerostomia, dysgeusia, oral hypoesthesia and throat discomfort, yet the current evidence base remains fragmented and inconsistently described. Dry mouth is not a trivial symptom in this setting. Salivary reduction can disturb oral buffering, impair tissue lubrication, and leave patients more vulnerable to caries, mucosal irritation and periodontal inflammation.
A brief symptom report can signal a broader change in oral homeostasis. In a patient population already managing metabolic disease, that shift has practical consequences for dental surveillance, hydration counseling and oral symptom triage.
Why salivary disruption matters in incretin-treated patients
The protocol frames the oral cavity as a biologically sensitive target rather than an incidental site of discomfort. Saliva maintains enamel protection, supports antimicrobial defenses, and reduces friction across mucosal surfaces. If incretin-based therapy alters salivary function, even indirectly, the downstream effects can accumulate quietly before they become clinically obvious. Xerostomia can impair chewing and swallowing, dysgeusia can reduce appetite and food enjoyment, and oral hypoesthesia may obscure early mucosal injury.
The review rationale also acknowledges that metabolic and inflammatory changes linked to GLP-1 and GIP signaling could influence oral tissues beyond simple dryness. That possibility is clinically relevant because patients taking these agents often have overlapping risk factors for oral disease, including diabetes itself, dietary change, and weight-loss-related shifts in intake patterns. The protocol does not claim causality; instead, it recognizes a plausible biological pathway that deserves structured mapping before clinicians dismiss these complaints as background noise.
Search strategy built to capture a scattered evidence base
The planned scoping review will follow JBI reporting guidance and includes a broad search strategy intended to catch both published and grey literature. Cochrane, LILACS, PubMed/MEDLINE, Scopus and Web of Science will be searched, with additional material drawn from Google Scholar and ProQuest Dissertations & Theses Global. The investigators will also use snowballing and expert consultation to identify studies that may not surface through standard indexing alone.
That approach fits a topic where adverse oral effects may be buried inside safety reports, observational studies, or small descriptive series rather than in large randomized trials. A narrow search would risk missing the very signal the review is meant to clarify. By accepting all languages and all publication dates, the protocol is positioned to capture the full historical record of incretin-related oral observations, including early reports that may predate current prescribing patterns.
The planned synthesis is narrative rather than quantitative, which is appropriate for a field where outcome definitions are likely to vary widely. When data permit, the review will make exploratory descriptive comparisons by therapeutic indication, separating type 2 diabetes from obesity, and by pharmacological class, distinguishing GLP-1 receptor agonists from GLP-1/GIP dual agonists. Semaglutide, liraglutide and tirzepatide are specifically named as agents of interest, and any available differences in dosage, duration and class exposure will be considered descriptively.
Tirzepatide, semaglutide and liraglutide will be examined descriptively
The protocol does not promise head-to-head comparisons or definitive safety ranking. Instead, it aims to organize a field that is currently difficult to interpret because adverse oral effects may be reported under different terms, in different contexts, and with varying levels of clinical detail. A patient experiencing a bitter taste, numbness, sore throat or dry mouth may not present with a neat, standardized adverse-event label. That inconsistency makes synthesis difficult but also makes it more important.
By placing tirzepatide and other incretin-based agents under the same analytical lens, the review may help identify whether oral complaints cluster by drug class, indication, or exposure pattern. If a signal is stronger in one subgroup, the distinction could influence how clinicians counsel patients at initiation and follow-up. If the reports are sparse or contradictory, that finding will be valuable as well because it would show where pharmacovigilance systems are still underpowered.
A protocol, not a result, but still clinically useful
This paper is a protocol, so it does not report pooled prevalence, comparative risk estimates, or final conclusions about oral harm. Its importance lies in the questions it organizes. The planned review could help clarify whether oral symptoms are isolated adverse events, underrecognized treatment effects, or manifestations of broader metabolic and inflammatory shifts associated with incretin therapy.
The protocol is registered prospectively on the Open Science Framework, which strengthens transparency and reduces the risk of post hoc outcome drift. Because the project will rely on previously published studies and secondary data, ethics approval was not required. Findings are intended for peer-reviewed publication and conference presentation once the review is complete.
For clinicians, the practical issue is already visible. Patients receiving incretin-based therapy may describe dry mouth, taste change, numbness or throat discomfort, and those complaints deserve a structured oral history rather than dismissal. For dental and medical teams alike, the absence of robust prevalence data is itself the signal: a common therapeutic class may be entering a part of the body where safety reporting has lagged behind prescribing growth.