Semaglutide does not raise risk for neurologic disorders for adults with type 2 diabetes
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Key takeaways:
- Adults with type 2 diabetes using semaglutide did not have higher risk for neurologic disorders vs. three other diabetes drugs.
- Semaglutide was linked with lower all-cause mortality risk than other drugs.
Semaglutide was not associated with increased risks for adverse neurologic or psychological disorders at 1 year compared with other diabetes drugs, according to data published in eClinicalMedicine.
In a retrospective analysis of data from adults with type 2 diabetes in the TriNetX US Collaborative Network database, researchers found those prescribed semaglutide (Ozempic, Novo Nordisk) did not have higher risks for 22 different neurologic or psychological outcomes compared with those using the DPP-IV inhibitor sitagliptin (Januvia, Merck), the SGLT2 inhibitor empagliflozin (Jardiance, Boehringer Ingelheim/Eli Lilly) and the sulfonylurea glipizide.
“Because the study is observational, we should not make the mistake of assuming causality between the exposure (semaglutide) and the outcomes (neurological and psychiatric disorders) measured,” Riccardo De Giorgi, MD, DPhil, MRCPsych, clinical lecturer in the department of psychiatry at University of Oxford in the U.K., told Healio. “Therefore, we must be careful before considering any clinical recommendation. However, this study contributes to a growing body of research that provides reassurance regarding potential adverse neuropsychiatric effects of semaglutide and similar medications.”
De Giorgi and colleagues collected data from adults diagnosed with type 2 diabetes within 1 month of an initial prescription for semaglutide from Dec. 1, 2017, to May 31, 2021. Propensity score matching was used to match semaglutide users with three separate comparator groups of adults prescribed sitagliptin, empagliflozin and glipizide. Diagnoses of 22 neurologic and psychological outcomes and all-cause mortality occurring within 1 year of the first medication prescription were collected.
There were 23,386 adults prescribed semaglutide matched with 23,386 people prescribed sitagliptin (mean age, 56.6 years; 48.6% women). The semaglutide group had lower risks for cognitive deficit (HR = 0.72; 95% CI, 0.64-0.8) and dementia (HR = 0.52; 95% Ci, 0.4-0.68) than the sitagliptin group. The risk for all-cause mortality was lower among semaglutide users than adults using sitagliptin (HR = 0.58; 95% CI, 0.5-0.66).
A group of 22,584 adults prescribed semaglutide was matched with 22,584 adults prescribed empagliflozin (mean age, 57.6 years; 48.9% women). Those using semaglutide had lower risks for nicotine dependence (HR = 0.77; 95% CI, 0.65-0.9) and all-cause mortality (HR = 0.86; 95% CI, 0.75-0.99) than the empagliflozin group.
The final analysis matched 19,206 adults prescribed semaglutide with 19,206 people prescribed glipizide (mean age, 56.3 years; 49.3% women). Semaglutide was associated with lower risks for cognitive deficit (HR = 0.72; 95% CI, 0.63-0.81; P < .0001), nicotine dependence (HR = 0.72; 95% CI, 0.61-0.85) and all-cause mortality (HR = 0.55; 95% CI, 0.47-0.64) compared with glipizide.
Semaglutide was not associated with higher risk for any outcomes compared with sitagliptin, empagliflozin or glipizide.
“We were pleased to see that semaglutide use seemed positively associated with a lower risk for cognitive deficit and nicotine use,” De Giorgi said. “This is because there are several other studies that have been looking at mechanisms of action of this medication and they quite consistently seem to suggest that semaglutide may have neuroprotective activity while also working on regulating the reward system of our brain. These mechanisms, when faulty, are likely implied in the disorders mentioned above. Therefore, it was good to see that evidence from preclinical and clinical research would line up with each other.”
De Giorgi cautioned the findings need to be confirmed in both clinical trials and in other population groups, including people with obesity and those with psychiatric disorders.
For more information:
Riccardo De Giorgi, MD, DPhil, MRCPsych, can be reached at riccardo.degiorgi@psych.ox.ac.uk.
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