Researchers used a new-user design and Cox proportional hazards models to compare treatment-related events classified with Medical Dictionary for Regulatory Activities terminology. After adjustment for measured factors, imeglimin was associated with a substantially higher risk of gastrointestinal events than sitagliptin, with an adjusted hazard ratio of 5.44 and a 95% confidence interval of 3.44–8.61. The strongest associations involved nausea, for which the adjusted hazard ratio was 15.34 (95% confidence interval, 3.50–67.23); diarrhea, with an adjusted hazard ratio of 7.90 (95% confidence interval, 2.54–24.62); and abdominal discomfort, with an adjusted hazard ratio of 6.02 (95% confidence interval, 1.47–24.58).

No statistically significant difference in hypoglycemia risk was observed between the groups. The adjusted hazard ratio for hypoglycemia with imeglimin relative to sitagliptin was 0.66, but its wide 95% confidence interval of 0.20–2.22 indicated substantial uncertainty. The authors cautioned that the limited number of hypoglycemia events reduced confidence in this comparison, meaning that the nonsignificant result should not be interpreted as proof that the drugs have identical risks.

A sensitivity analysis restricted to patients receiving monotherapy produced a similar association: the hazard ratio for gastrointestinal events with imeglimin was 5.36, with a 95% confidence interval of 2.63–10.92. The findings concern Japanese clinical practice and selected patients who received newly prescribed medicine through community pharmacies during 2022–2024. Because the study was retrospective and observational, it can identify associations but cannot establish that imeglimin caused the additional events; unmeasured differences between patient groups may also have contributed. Nevertheless, the data indicate that gastrointestinal adverse events were more common among imeglimin users than among comparable new users of sitagliptin, while the evidence was insufficient to draw a firm conclusion about hypoglycemia.

Subject of Research: Comparative real-world safety of imeglimin and sitagliptin in Japanese patients with type 2 diabetes

Article Title: Comparative safety of imeglimin versus sitagliptin in Japanese patients with type 2 diabetes: A pharmacy-based retrospective cohort study

Article References: Suzuki, N., Ooba, N., Nakajima, R., Takabatake, K., Saita, M., Kawakami, E., Kawana, M., Watanabe, D., & Hashiba, H. (2026). Comparative safety of imeglimin versus sitagliptin in Japanese patients with type 2 diabetes: A pharmacy-based retrospective cohort study. PLOS One, 21(10), e0359960. https://doi.org/10.1371/journal.pone.0359960

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0359960

Keywords: imeglimin, sitagliptin, type 2 diabetes, adverse events, gastrointestinal events, hypoglycemia, pharmacy records, Japan, retrospective cohort, drug safety, Comparative, safety