Smell and Taste Disturbances Among Glucagon-Like Peptide-1 Receptor Agonist Users.

Importance: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have gained popularity over the last decade for both glycemic control and weight loss. Although various adverse events have been reported among GLP-1 RA users, little is known regarding their potential impact on smell and taste perception.

Objective: To evaluate the association between GLP-1 RAs and smell and taste disturbances.

Design, setting, and participants: This large-scale multicenter retrospective cohort study used electronic health records from a large electronic health records database (TriNetX Global Collaborative Network) from December 5, 2017, to April 20, 2026 (date of analysis), with follow-up of up to 2 years after treatment initiation. Patients (aged ≥18 years) diagnosed with type 2 diabetes (T2D) with no record of smell or taste disturbances were divided into 2 groups: the control group comprised patients prescribed T2D medications without GLP-1 RA exposure and the exposure group consisted of patients who received a GLP-1 RA prescription after their first recorded diagnosis of T2D. Propensity score matching was applied to balance demographic, clinical, and socioeconomic differences.

Exposure: GLP-1 RA or different antidiabetic medications.

Main outcomes and measures: The primary outcome was incident smell and taste disturbances, identified using International Classification of Diseases (ICD) codes, assessed overall and separately during a follow-up period of 3 months to 2 years. Hazard ratios (HRs) and 95% CIs were estimated using Cox regression analyses to evaluate the risk of incident cases.

Results: After matching, each cohort included 438 474 patients (GLP-1 RA: mean [SD] age, 57.7 [12.2] years; 240 620 females [54.9%]; control: mean [SD] age, 57.6 [13.4] years; 245 730 females [56.0%]). Patients with documented GLP-1 RA therapy had an increased risk of overall smell and taste disturbances (HR, 1.48; 95% CI, 1.37-1.61) compared with matched control patients. When stratified by outcome, GLP-1 RA use was associated with a higher risk of smell (HR, 1.81; 95% CI, 1.58-2.07) and taste (HR, 1.52; 95% CI, 1.35-1.71) disturbances. These findings were consistent throughout the follow-up period.

Conclusions and relevance: This study suggests that GLP-1 RA therapy is associated with a higher risk of smell and taste disturbance, highlighting the need for closer monitoring and greater public health awareness. Future research is required to validate these findings and to further explore the mechanisms underlying this association.