by Ahmad Mohammad

Graphic design by Qingyue Guo

Millions of people are taking a weight-loss drug that may do more than slim their waistlines.¹
The explosive growth of glucagon-like peptide 1 (GLP-1) mimicking drugs represents a breakthrough for weight and diabetes management. Beneath this success story, however, lies a far more profound discovery that is only now coming into focus: these drugs could be protecting users’ brains from Alzheimer’s disease (AD), but females and males may not reap the same benefits.

Drugs that act like GLP-1 in the body (GLP-1 mimetics) appear to shield the brain from AD in unexpected ways, however, the protection offered by these medications is not uniform.¹ Females and males taking identical doses of this drug family experience strikingly different outcomes,² raising the question—if a medication can protect your brain but works differently depending on your sex, how can we ensure everyone who could benefit receives the help they need?

Originally developed in the 1990s as a diabetes treatment, GLP-1 mimetics were designed to mimic a naturally occurring hormone that signals fullness and prompts your body to lower blood sugar.³ These compounds have recently grown in popularity due to their role as the active ingredient in drugs like Ozempic.³ What no one anticipated as their use increased, however, was how these drugs could affect the brain or even change diagnosis rates for diseases throughout the lifespan. In 2024, researchers analyzed the electronic health records of 116 million US patients and observed that those with type 2 diabetes using GLP-1 mimetics showed lower AD diagnosis rates compared to those on other antidiabetic drugs.⁴ Furthermore, this effect was more potent in females, which is crucial when it comes to AD as two-thirds of cases are in female patients.⁴

As with many diseases and treatments, a much more complicated picture emerged when preclinical studies carefully compared sex differences. Female mice given GLP-1 mimetics showed more pronounced improvements in memory than male mice given an identical dose.⁵ Despite these benefits, females are more likely to abruptly discontinue use, a pattern that has been attributed to their higher rates of nausea and vomiting.⁶ 

This realization created a painful paradox: the population that may experience the greatest cognitive benefits from GLP-1 mimetics are also the population most likely to experience side effects severe enough to prevent them from accessing those benefits. 

Research increasingly points to estrogen as a likely central player in this puzzle. Estrogen levels fluctuate throughout a person’s life depending on age, menstrual cycle phase, and menopausal status.⁷ Evidence suggests these changes in estrogen levels may impact how GLP-1 mimetics affect brain function. In fact, females taking the medication during phases when estrogen levels are naturally higher showed greater cognitive benefits, but more intense side effects.² While this hormonal interplay has profound implications for all females currently using these drugs, this knowledge has barely penetrated mainstream discussions.² Despite nearly three million Canadians currently or previously taking GLP-1 mimetics, the potential interplay with estrogen remains understudied and rarely discussed.⁸

What makes these findings particularly urgent for middle-aged adults is emerging evidence suggesting that there may be a critical window of prevention. A 2025 review found that the most drastic cognitive benefits of GLP-1 mimetics were in those aged 40 to 60 who have elevated body weight, regardless of AD risk.¹ Those who already have an AD diagnosis, on the other hand, showed only modest improvements in cognition.¹ These findings suggest that early intervention with GLP-1 mimetics, before significant neurological damage has accumulated, may be substantially more effective than treatments started after symptoms have emerged.

“If you wait until someone has memory issues, it is probably too late,” says Dr. Bonnie Lee, a postdoctoral researcher in the lab of Dr. Liisa Galea at the Centre for Addiction and Mental Health. Dr. Lee further stresses the importance of timing to reap the protective benefits of these drugs: “The most exciting possibility is using these drugs for prevention or very early intervention, before damage has occurred. That is where we are seeing the most impressive results. And that is where the sex differences become clinically important. Females may get better protection, but only if we figure out how to give them the medication in a way they can tolerate.”

The conversation around GLP-1 mimetics should encompass not only their potential benefits for weight loss and blood sugar regulation but also their effects on the brain. Females especially should consider this decision with clear information about both the potential cognitive benefits and the nausea-related side effects they may experience. 

The key takeaway is not that GLP-1 mimetics can universally prevent AD. Rather, these medications may help certain people, and the research should consider that sex and metabolic health are important factors in predicting who will benefit most and who has a higher chance of struggling with side effects. 

As research continues, it further highlights that GLP-1 mimetics act in ways that are far more intricate than the headlines suggest. The answers matter not just for those considering the drugs today, but for countless others worried about memory, healthy aging, and what the future holds for their brains. 

References

1. Chuansangeam, M., Phadungsaksawasdi, P., Park, H. J., et al. Exploring the link between GLP-1 receptor agonists and dementia: A comprehensive review. J Alzheimers Dis Rep 9, 25424823251342182 (2025).

2. Börchers, S. & Skibicka, K. P. GLP-1 and Its Analogs: Does Sex Matter? Endocrinology 166, bqae165 (2025).

3. Popoviciu, M. S., Păduraru, L., Yahya, G., et al. Emerging Role of GLP-1 Agonists in Obesity: A Comprehensive Review of Randomised Controlled Trials. Int J Mol Sci 24, 10449 (2023).

4. Wang, W., QuangQiu, W., Qi, X., et al. Associations of semaglutide with first-time diagnosis of Alzheimer’s disease in patients with type 2 diabetes: Target trial emulation using nationwide real-world data in the US. Alzheimers Dement 20, 8661–8672 (2024).

5. Richard, J. E., Mohammad, A., Go, K., et al. Sex-specific metabolic and central effects of GLP-1–estradiol conjugate in middle-aged rats on a standard or western diet. Brain, Behavior, and Immunity 130, 106088 (2025).

6. Sikirica, M. V., Martin, A., Wood, R., et al. Reasons for discontinuation of GLP1 receptor agonists: data from a real-world cross-sectional survey of physicians and their patients with type 2 diabetes. Diabetes Metab Syndr Obes 10, 403–412 (2017).

7. Yu, Z., Jiao, Y., Zhao, Y., et al. Level of Estrogen in Females—The Different Impacts at Different Life Stages. Journal of Personalized Medicine 12, 1995 (2022).

8. Harris, E. Poll: Roughly 12% of US Adults Have Used a GLP-1 Drug, Even If Unaffordable. JAMA 332, 8 (2024).