The use of GLP-1 receptor agonists (RAs) in treating type 2 diabetes is associated with a relatively low but notable risk for reduction in smell and taste sensations, new research showed.

“Clinicians and patients should be aware of the potential smell and taste disturbances among GLP-1 RA users,” reported the authors in research published this week in JAMA Otolaryngology-Head & Neck Surgery.

However, “while a 38% higher risk of these disturbances was observed, the absolute risk remained low; therefore, discontinuation of therapy should not be routine and should instead be guided by shared decision-making, considering the overall clinical context,” the authors added.

Even in the absence of GLP-1 RA treatment, type 2 diabetes has been associated with the potential for smell and taste disturbances, with speculated causative factors including diabetic neuropathy and microvascular complications of the disease, the authors reported.

However, with GLP-1 RA use known to have effects on key areas of chemosensory function, including the olfactory bulb and taste buds, the authors sought to further investigate how and whether those effects exacerbate symptoms in people with type 2 diabetes.

For the multicenter, retrospective cohort study, they utilized the TriNetX health records database, identifying patients with type 2 diabetes who were treated between December 2017 and April 2026 and had a follow-up of up to 2 years following treatment initiation.

The patients were divided equally into two groups of 438,474 patients each, with a control group consisting of patients prescribed type 2 diabetes medications without the use of GLP-1 RAs and an exposure group of those treated with GLP-1 RAs following their first recorded diagnosis of type 2 diabetes.

The two groups were propensity score matched according to demographic, socioeconomic, and clinical differences: GLP-1 RA group (mean age, 57.7 years; 54.9% female) and non-GLP-1 RA group (mean age, 57.6 years; 56% female).

With a mean follow-up of 730 days in each group, the patients in the GLP-1 RA therapy group showed significant increases in the overall risk for smell and taste disturbances, as indicated by International Classification of Diseases codes (0.37% vs 0.22% in the GLP-1 RA group vs the control group; hazard ratio [HR], 1.48; P < .0001), corresponding to an absolute risk index of 0.15% and a number needed to harm of 670. 

Taste disturbances, specifically, occurred in 0.18% vs 0.10% of those in the GLP-1 RA group vs the control group (HR, 1.52), and smell disturbances were observed in 0.15% vs 0.07%, respectively (HR, 1.81; P < .0001 for each), with the increases sustained throughout the study follow-up period. 

When further stratified by specific smell disorders, anosmia, or a complete loss of the sense of smell, occurred in 0.13% vs 0.07% of patients in the GLP-1 RA cohort vs the control cohort, whereas parosmia, or a distorted sense of smell, occurred in 0.05% vs 0.02% of patients in the GLP-1 RA cohort vs the control cohort (P < .0001 for both). 

The study didn’t evaluate factors associated with the taste and smell disturbances, co-author Nir Zontag, of Hadassah Medical Center, Faculty of Medicine, Hebrew University, Jerusalem, Israel, told Medscape Medical News.

“Subgroup analyses as well as evaluation of additional risk factors may be of interest for future studies,” he said.

While the absolute risk was small, smell and taste symptoms can notably have important clinical relevance, with such sensory perception disturbances having been linked to potentially serious outcomes, including neurodegenerative diseases and increased mortality.

“Among patients with type 2 diabetes, these disturbances could suggest early predictors of diabetes-related complications,” the authors noted.

However, considering the established benefits of GLP-1 RA therapy for glycemic control and broader cardiometabolic outcomes, careful assessment is urged if patients do report disturbances, the authors noted.

“In patients who develop such symptoms, clinicians should first follow standard diagnostic evaluation and avoid prematurely attributing symptoms to GLP-1 RA use,” they wrote.

Prior Research Shows GLP-1-Related Taste Disturbances — but Also Enhancements

Previous research also linking taste and smell disturbances to GLP-1 RA use includes one study of FDA data from the Adverse Event Reporting System database showing taste disturbances with a reported odds ratio (ROR) of 12.9 with semaglutide and 3.8 with tirzepatide and an ROR of anosmia of 3.4 with semaglutide.

Conversely, however, other research has reported notable increases in sensory perception, specifically regarding the taste of salty and sweet foods, associated with GLP-1 RA use, with the authors of that study speculating a possible link to a favorable treatment response.

Zontag noted that he was not aware of any data similarly suggesting the smell and taste disturbances, such as those in the current study, may also play a role in the drugs’ weight-loss effects.

Smell-Boosting Intervention?

For patients reporting such symptoms, however, Zontag noted a recent study suggesting that olfactory dysfunction may be modifiable in patients with type 2 diabetes through a relatively easy, home-based intervention, consisting of a twice-daily routine of 6-minute exposure to six odorants — rose, eucalyptus, lemon, clove, coffee, and cinnamon.

While the study focused on patients with type 2 diabetes-related mild cognitive impairment, and the intervention did show improvement in cognitive measures, the olfactory training also importantly further showed elevated overall olfactory performance.

Risks vs Benefits

The authors of an editorial accompanying the new study agree that the findings should be considered in the context of the need for the potential benefits of GLP-1 RAs.

“For patients with uncontrolled diabetes, cardiovascular disease, or severe obesity, the risk of adverse effects, including sensory disturbance, may be acceptable,” they wrote. “However, when used for marginal weight loss or cosmetic purposes, an equivalent probability of harm may be weighted differently.”

“This cost-benefit discussion should be tailored to the individual to yield a comprehensive assessment,” the editorial authors added. “The acceptable risk threshold will change depending on whether the drug is used to treat disease, prevent disease, or satisfy a societal demand.”

Editorial co-author Edward D. McCoul, MD, MPH, professor and vice chair of Adult ENT Services and director of Rhinology and Sinus Surgery in the Department of Otorhinolaryngology at the University of Queensland-Ochsner Clinical School, New Orleans, added to Medscape Medical News that the study’s caveats further include various population-based confounders.

“It is difficult to account for differences in environment, genetics, and dietary habits that may occur in other populations,” he pointed out. “The study controlled for demographic, clinical, and socioeconomic factors, but some things cannot be controlled for.”

Nevertheless, McCoul said the findings will be considered in his clinical practice moving forward.

“We have not been tracking sensory dysfunction in our GLP-1 patients,” McCoul said.

“But now with this study I intend to enter discussion with our endocrinology and bariatric providers to institute a system for counseling and reporting these outcomes.”

The authors reported having no disclosures. McCoul reported receiving personal fees from 3-D Matrix, Advanced Rx, Sanofi, and Regeneron and owning stock options from Zsquare outside the submitted work.