- Diabetes patients using GLP-1 agents had a higher risk of smell and taste disturbances over 2 years, though absolute risk increases were very small.
- Smell disturbances included anosmia and parosmia; taste disturbances included parageusia.
- Incident smell and taste disturbances were identified solely using ICD codes which are often assigned based on patient-reported symptoms, not objective testing.
Use of GLP-1 receptor agonists was associated with a higher risk of smell and taste disturbances among adults with type 2 diabetes, an analysis of electronic health record (EHR) data suggested.
Compared with matched controls using other antidiabetic agents, GLP-1 medication users had a 48% increased risk of overall smell and taste disturbances over a 2-year follow-up period (HR 1.48, 95% CI 1.37-1.61), according to Nir Zontag, BSc, and Jonathan Zontag, BSc, both of the Hadassah Medical Center at Hebrew University in Jerusalem, Israel.
GLP-1 drug users had higher risks for both smell disturbances (HR 1.81, 95% CI 1.58-2.07), and taste disturbances (HR 1.52, 95% CI 1.35-1.71). However, these corresponded to relatively small absolute risk increases of 0.08% and 0.07%, respectively, the researchers reported in JAMA Otolaryngology-Head & Neck Surgery.
Smell disturbances included anosmia and parosmia; taste disturbances included parageusia.
"These findings suggest a potential multifactorial association, possibly involving both peripheral sensory receptors and central neural pathways," Zontag and Zontag wrote. "The increase in popularity of GLP-1 receptor agonists for both glycemic control and obesity raises questions of their potential effects on chemosensory function, given the presence of GLP-1 receptor agonists in both the olfactory bulb and taste buds."
GLP-1 receptor agonists are highly effective for glycemic control and weight loss but their rapid rise in popularity has been accompanied by emerging safety concerns, including risks for eye conditions and otolaryngologic adverse events.
Zontag and Zontag noted that while smell and taste disturbances are of growing interest in patients with diabetes, they traditionally have been attributed to underlying diabetic neuropathy and microvascular complications. However, the current findings align with recent case reports suggesting the drugs themselves might play a role in sensory dysfunction, they noted.
Olfactory and gustatory dysfunction are important markers of systemic well-being, noted accompanying commentary authors Charles Riley, MD, of Boston University in Massachusetts, and Edward McCoul, MD, MPH, of Ochsner Clinic Foundation in New Orleans.
"Olfactory dysfunction is one of the most reliable prodromal markers for neurodegenerative conditions such as Parkinson's disease and Alzheimer's disease," they wrote. "Taken together, smell and taste are an essential sensory warning system, alerting one to environmental dangers or spoiled foods."
The editorialists emphasized the need for improved counseling, surveillance, and shared decision-making when prescribing GLP-1 drugs. For patients with uncontrolled diabetes, cardiovascular disease, or severe obesity, the benefits of the medication may outweigh the risk of sensory disturbance, they said.
They also recommended that clinicians ask questions about baseline sensory ability before prescribing GLP-1 agents. "These questions should include a subjective assessment of smell and taste, documentation of risk factors, and counseling about the potential risk of smell loss," Riley and McCoul advised. Validated tools like the Smell Identification Test could be used for high-risk patients and the risk-benefit calculation could be re-evaluated if olfactory loss occurs, with patients referred to an otolaryngologist if necessary.
"We are likely in the early stages of a profound therapeutic shift, with significant clinical and mechanistic frontiers yet to be explored," they concluded. "Prospective studies with baseline smell testing, dose-response and duration-response analyses, and a focus on specific drugs are future steps that warrant study."
In their retrospective study, Zontag and Zontag analyzed medical records of adults in the TriNetX Global Collaborative Network from December 2017 to April 2026 who were diagnosed with type 2 diabetes and had no history of prior smell or taste disturbances.
The exposure group received a GLP-1 receptor agonist while the control group was prescribed diabetes medications -- SGLT2 inhibitors, DPP-4 inhibitors, sulfonylureas, thiazolidinediones, metformin, insulin, or α-glucosidase inhibitors -- without a GLP-1 drug.
After propensity-score matching, each group had 438,474 patients. The average age was approximately 58, and 55% were female.
The researchers acknowledged certain limitations. Incident smell and taste disturbances were identified solely using ICD codes. "This is particularly relevant for these diagnoses, which are often assigned based on patient-reported symptoms rather than on standardized objective testing," Zontag and Zontag pointed out.
"Self-reported measures of smell and taste are inherently subjective and may not accurately represent true sensory function, as they can be influenced by individual perception and broader health factors, affecting diagnostic accuracy," they wrote.
In addition, all GLP-1 agents were grouped into one category despite their molecular differences that could have distinct effects, the researchers said.
Disclosures
Zontag and Zontag reported no disclosures.
McCoul reported personal fees from 3D Matrix, Advanced Rx, Sanofi/Regeneron, and stock in Zsquare. Riley reported no disclosures.
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