SGLT2 Inhibitors Did Not Appear to Alter Risk of Parkinson Disease Onset

When treating patients with chronic kidney disease (CKD), diabetes, or heart failure, sodium-glucose cotransporter-2 (SGLT2) inhibitors did not appear to significantly alter the risk of Parkinson disease. These findings, which were presented at the American Academy of Neurology 2026 Annual Meeting, support their neurological safety; however, the authors note that longer follow-ups and dedicated neurodegenerative outcome trials are needed to confirm these outcomes.¹

SGLT2 inhibitors, including canagliflozin (Invokana; Janssen Pharmaceuticals), dapagliflozin (Farxiga; AstraZeneca), empagliflozin (Jardiance; Eli Lilly and Company, Boehringer Ingelheim), and ertugliflozin (Steglatro; Merck), have transformed the type 2 diabetes space by providing glucose-lowering efficacy coinciding with cardiovascular and renal protection. Although these therapies were initially approved as adjuncts to diet and exercise for glycemic control, they have expanded indications that include reducing hospitalizations related to heart failure, preserving renal function, and lowering cardiovascular mortality in patients with or without diabetes.²

The mechanism of action of SGLT2 inhibitors involves inhibiting glucose reabsorption within the proximal renal tubules, resulting in glucosuria, modest weight loss, and blood pressure reduction. Prior evidence establishes the benefits in heart failure with reduced or preserved ejection fraction and in CKD, supporting their incorporation into major international guidelines. Despite their substantial clinical advantages, therapy requires attention to safety considerations (eg, volume depletion, genital infections, diabetic ketoacidosis, and potential lower extremity complications). It is critical to optimize patient outcomes based on appropriate selection, dosing, monitoring, and interprofessional strategies that enhance adherence and long-term care.²

The abstract authors wrote that preclinical studies have suggested neuroprotective effects of SGLT2 inhibitors; however, because of the shared metabolic inflammatory and metabolic pathways between diabetes and Parkinson disease, these therapies may influence the risk of Parkinson disease onset.¹

For this study, the investigators initiated a systematic search of ClinicalTrials.gov to identify randomized controlled trials reporting Parkinson disease incidence in treatment groups who received SGLT2 inhibitors. There were no eligible data found for ertugliflozin, enavogliflozin (Envlo; Daewoong Pharmaceutical Co), henagliflozin (Jiangsu Hengrui Pharmaceuticals), ipragliflozin (Astellas Pharma, Kotobuki Pharmaceutical), luseogliflozin (Taisho Pharmaceutical), or tofogliflozin (Chugai Pharmaceutical).¹

The authors reported that pooled odds ratios (OR) with 95% confidence intervals (CI) were calculated using a random-effects Mantel-Haenszel model, and heterogeneity was assessed with the I² statistic.¹

A total of 14 trial arms across 12 unique studies that consisted of about 64,000 patients (follow-up: 7–50 months) were included in the analysis. Two trial arms were excluded from pooled analysis because there were not any events in those groups.

According to the authors, the pooled OR for Parkinson disease was about 0.55 ([95% CI, 0.27–1.12]; p = .20). Heterogeneity was negligible (I² = 0%), and the prediction interval ranged from about 0.23 to 1.50. Further, subgroup analyses showed no significant effect for individual agents: 10 mg of empagliflozin (OR 0.64 [95% CI, 0.17–2.43]), 25 mg of empagliflozin (OR 0.33 [95% CI, 0.01–8.15]), 10 mg of dapagliflozin (OR 0.33 [95% CI, 0.09–1.23]), sotagliflozin (OR 0.25 [95% CI, 0.03–2.24]), 100 mg of canagliflozin (OR 3.00 [95% CI, 0.31–28.81]), and bexagliflozin (OR 1.50 [95% CI, 0.06–36.99]). The authors reported no evidence of publication bias was detected during their analysis.

For pharmacists, these findings reinforce that SGLT2 inhibitors continue to demonstrate a favorable safety profile, including no significant association with Parkinson disease based on current evidence. This should reassure pharmacists when evaluating long-term risks in patients with diabetes, CKD, or heart failure; however, given the lack of statistical significance and relatively short follow-up periods, these findings should be interpreted cautiously rather than as definitive evidence of neutrality or benefit. Pharmacists should also continue prioritizing established indications while remaining aware of emerging research on potential neurologic effects, especially as preclinical data suggest possible neuroprotection that has not yet been confirmed clinically.

In practice, they play a critical role in patient selection, safety monitoring, and interprofessional collaboration. They should counsel patients on known risks—such as volume depletion, genitourinary infections, and diabetic ketoacidosis—while remaining attentive to any new or worsening neurologic symptoms. Pharmacists can also help contextualize evolving data for prescribers, supporting evidence-based decision-making without premature changes in therapy. Additionally, by reinforcing the well-established cardiovascular and renal benefits of SGLT2 inhibitors and addressing patient concerns, pharmacists help improve adherence and optimize long-term outcomes while the evidence base on neurologic effects continues to evolve.

REFERENCES

1. Alexander T, Pitton Rissardo J, Fornari Capara AL, Walker I. Do SGLT2 Inhibitors Influence Parkinson’s Disease Risk? A Meta-analysis of Randomized Trials. Presented at: American Academy of Neurology 2026 Annual Meeting. Chicago, Illinois; April 18-22.

2. Padda IS, Mahtani AU, Parmar M. Sodium-glucose transport 2 (SGLT2) inhibitors. StatPearls [Internet]. Updated September 15, 2025. Accessed April 20, 2026. https://www.ncbi.nlm.nih.gov/books/NBK576405/