Smells Like Neurodegeneration: GLP-1 Drugs Linked to Taste and Smell Disturbance

Are the blockbuster weight loss drugs accelerating neurological decline?

In last week’s post, I covered a report on the concerning finding that GLP-1 receptor agonist drugs like Wegovy and Ozempic may cause users to engage in less spontaneous movement and exercise, thus setting them up for weight regain and physical frailty. Hard on the heels of that worrying news comes a new paper carrying the alarming message that the blockbuster weight loss drugs appear to increase the risk of taste and smell disturbances, and that these sensory disturbances may reflect neurological damage.

The study, published in JAMA Otolaryngology - Head & Neck Surgery, analysed electronic health records from the TriNetX Global Collaborative Network. TriNetX is a large database of electronic health records from “more than 13,000 clinical sites across 20+ countries worldwide”.

Researchers first pulled deidentified medical records of 438,474 patients with type 2 diabetes who had received at least two prescriptions for a GLP-1 drug. They then trawled the database to find 438,474 type 2 diabetic patients who were taking at least one other type of diabetes medication, but had not used GLP-1s. This second group was matched to the GLP-1-using cohort in terms of demographic characteristics, comorbidities, socioeconomic risk factors, nicotine dependence, and prior surgical procedures. Patients in both groups had no documented history of taste or smell disturbances as of December 2017, the date chosen as the study’s baseline. Then, the researchers compared the rate of new onset of smell and taste disturbances in the GLP-1 users and non-users, over the following two years.

(As an aside, this is one example of an appropriate and worthwhile use of artificial intelligence. A well-constructed algorithm can rapidly trawl through mountains of data that would take a whole team of humans several months, or even years, to process, enabling detection of drug safety signals that might otherwise not be picked up for decades. Whether these safety signals are acknowledged and acted upon by regulatory bodies and prescribing physicians, is another matter entirely, as we learned during the manufactured COVID crisis.)

You might be wondering why the researchers focused on diabetic patients. Amid all the hoopla around GLP-1 receptor agonists as weight loss drugs, it’s easy to forget that they began life as an adjunctive treatment for type 2 diabetics who do not achieve adequate blood glucose control on metformin - the first-line medical treatment for the condition - or who cannot tolerate it. The problem is, GLP-1 receptor agonists may be giving diabetics better numbers on their blood tests, while failing to prevent diabetic complications such as nerve damage... or perhaps even accelerating the development of complications, at least in some patients.

So what is the connection between taste and smell disturbances, and diabetic complications? Diabetes is characterised by persistently high blood glucose levels, which cause damage to both nerves - known as diabetic neuropathy - and to small blood vessels - microvascular complications. Diabetics are known to be at higher risk of smell and taste disturbances, and it is believed that these sensory disorders are caused by diabetic neuropathy and microvascular damage. Moreover, taste and smell disturbances aren’t just inconveniences, or minor threats to one’s quality of life. They are indicators of neurodegenerative disease and predictors of shortened lifespan in both the general population, and specifically in diabetics. Smell or taste disorders in diabetics are a marker of worsening health and higher risk of more severe - and potentially life-shortening - complications.

So what exactly did the researchers find? Overall, the risk of smell and taste disorders was increased by 48 per cent in diabetics who had used a GLP-1 receptor agonist. When broken down into separate categories, risks were as follows:

• Olfactory disorders (disorders of the sense of smell): 81 per cent higher

  • Anosmia (complete loss of the sense of smell): 78 per cent higher

  • Parosmia (distorted sense of smell): 118 per cent higher, or more than double the risk

• Gustatory disorders (disorders of the sense of taste): 52 per cent higher.

Figure 2. Dot-and-Whisker Plot Showing for Smell and Taste Disturbances Over 2 Years. HRs with 95% CIs are shown for the risk of new onset of smell and taste disturbances in patients with T2D treated with GLP-1 RAs vs other antidiabetic medications, over a 2-year follow-up. GLP-1 RA indicates glucagon-like peptide-1 receptor agonist; HR, hazard ratio; T2D, type 2 diabetes. From ‘Smell and Taste Disturbances Among Glucagon-Like Peptide-1 Receptor Agonist Users.’

It’s important to point out that while GLP-1 users had a substantially increased relative risk of taste and smell disturbances, the absolute risk increase was relatively small - just 0.15 per cent. (For a concise explanation of relative vs absolute risk, see my previous article Fear-based medicine and the concept of risk.) In more easily relatable terms, that’s a number needed to harm (NNH) of 670 - that is, 670 type 2 diabetic patients would have to use at least two prescriptions of a GLP-1 receptor agonist, for one of them to develop a taste or smell disturbance.

However, this may be an underestimate of the magnitude of the effect, for two reasons:

1. Patients may not necessarily report disturbances of taste and smell to their doctor, perhaps because they don’t think it’s serious enough to mention, or they attribute it to ‘getting older’, or they assume it’s pointless to discuss because nothing could be done about it anyway.

2. Doctors may not use the correct International Classification of Diseases (ICD) code for the smell or taste disorder on the patient’s electronic medical record. The researchers used these ICD codes to identify patients who had developed taste and smell disturbances during the two year follow-up period.

But even if no more than one in every 670 GLP-1 drug users is afflicted by a taste or smell disturbance, it’s still an adverse effect that should be taken seriously.

Losing one’s sense of smell and/or taste, or having a distorted sense of smell or taste, impacts greatly on quality of life. I saw several clients who lost their sense of smell after getting COVID-19. All of them reported that not being able to smell food, or household odours, or the scents of nature, or their loved ones’ distinctive aromas, was profoundly distressing and disorientating. And altered or absent taste and smell perception can make it extremely difficult for a diabetic to follow a healthy diet, which is, of course, the most impactful step they can take to get their diabetes under control.

Photo by Elly Johnson on Unsplash

Perhaps most importantly, as mentioned previously, taste and smell disorders are an indicator of damage to the nerves involved in processing this sensory information, and hence are potentially early predictors of diabetic neuropathy. Let’s not forget that patients with diabetes take GLP-1 receptor agonists because their doctors tell them that by helping them achieve better blood glucose control, the drugs will stave off diabetic complications. But if taste and smell disorders are occurring at a higher rate in GLP-1 users than in patients taking other diabetic medicines, these drugs may be increasing the risk of diabetes-related neurological problems.

The bottom line

I’ve written before about the misnomer of drug ‘side effects’. The desirable effects of a drug are described as its actions, while the undesirable ones are dubbed side effects or adverse effects. But in reality, all of the drug’s actions are effects, and more to the point, they’re all effects of interference with human physiology. If you’re sick, you can’t drug yourself back to good health, because health comes from healthful living. This is an immutable law of nature. Drugging people who became overweight and/or diabetic because they weren’t living healthfully, rather than addressing the causes of their condition is, in my opinion, completely insane.

As I wrote in The dark side of weight loss: Are GLP-1 agonists putting patients at risk for blindness, depression and suicidal thinking?, no less than 26 so-called ‘anti-obesity’ medications have been pulled from the market since 1964, because of safety issues ranging from toxicity to the heart and liver, to drug abuse and dependence, to psychiatric issues, to stroke and cancer... and the ultimate safety issue, namely death. GLP-1 receptor agonists may eventually face the same fate, but given the record profits they’re generating for the pharmaceutical industry, I’d say it’s odds-on that they will only be withdrawn after they’ve injured or killed millions of people.

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For information on my private practice, please visit Empower Total Health. I am a Certified Lifestyle Medicine Practitioner, with an ND, GDCouns, BHSc(Hons) and Fellowship of the Australasian Society of Lifestyle Medicine.