Comparative safety of imeglimin versus sitagliptin in Japanese patients with type 2 diabetes: A pharmacy-based retrospective cohort study
4 affiliations
- 1Department of Pharmacoepidemiology, Nihon University School of Pharmacy, Funabashi, Chiba, Japan
- 2Department of Pharmacy Practice in Primary Care, Nihon University School of Pharmacy, Funabashi, Chiba, Japan
- 3Japan Pharmaceutical Association, Shinjuku-ku, Tokyo, Japan
- 4Department of Pharmaceutical Sciences, Teikyo University School of Pharmacy, Itabashi-ku, Tokyo, Japan
Abstract
Clinical evidence supports the safety and efficacy of imeglimin, a new oral antidiabetic medication that increases insulin secretion and reduces insulin resistance. However, comparative real-world safety data with dipeptidyl peptidase-4 inhibitors, widely used in Japan, remain limited. This retrospective, pharmacy-based cohort study compared the incidence of adverse events (gastrointestinal events and hypoglycemia) among patients newly prescribed imeglimin or sitagliptin in real-world settings. Using a new-user design, we analyzed the 2022–2024 community pharmacy data across Japan, including 1,140 and 990 new imeglimin and sitagliptin users, respectively. Primary outcome (incidence of treatment-related events classified using Medical Dictionary for Regulatory Activities terminology) was evaluated using Cox proportional hazards models. Unadjusted and multivariable-adjusted hazard ratios (aHRs) for events during a 4-month follow-up were estimated. At least one adverse event was reported among 31% of imeglimin users versus 22% of sitagliptin users. Hypoglycemia risk differed non-significantly between groups (aHR: 0.66; 95% confidence interval [CI]: 0.20–2.22). However, imeglimin was associated with substantially higher risks of gastrointestinal events than sitagliptin (aHR: 5.44; 95% CI: 3.44–8.61), particularly nausea (aHR: 15.34; 95% CI: 3.50–67.23), diarrhea (aHR: 7.90; 95% CI: 2.54–24.62), and abdominal discomfort (aHR: 6.02; 95% CI: 1.47–24.58). Sensitivity analyses in patients receiving monotherapy yielded increased risk (hazard ratio (HR): 5.36; 95% CI: 2.63–10.92). Imeglimin use was associated with a higher incidence of gastrointestinal events than sitagliptin in Japanese clinical practice, closely approaching our prespecified threshold for clinical significance. Conversely, no significant difference was observed in hypoglycemia risk, although this finding should be interpreted with caution owing to the limited number of events. Involving community pharmacists allowed for active monitoring and identification of events that are often underreported in large-scale claims databases. Clinicians should prioritize gastrointestinal monitoring during initial stages of imeglimin therapy, particularly in older patients with complex treatment regimens.
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BibTeX
@article{suzuki2026comparative,
title = {{Comparative safety of imeglimin versus sitagliptin in Japanese patients with type 2 diabetes: A pharmacy-based retrospective cohort study}},
author = {Nao Suzuki and Nobuhiro Ooba and Rie Nakajima and Kasumi Takabatake and Masahiro Saita and Eiji Kawakami and Michiyo Kawana and Daiki Watanabe and Hajime Hashiba},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0359960},
url = {https://doi.org/10.1371/journal.pone.0359960},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Comparative safety of imeglimin versus sitagliptin in Japanese patients with type 2 diabetes: A pharmacy-based retrospective cohort study
AU - Nao Suzuki
AU - Nobuhiro Ooba
AU - Rie Nakajima
AU - Kasumi Takabatake
AU - Masahiro Saita
AU - Eiji Kawakami
AU - Michiyo Kawana
AU - Daiki Watanabe
AU - Hajime Hashiba
PY - 2026
DA - 2026/10/07
JO - PLOS One
DO - 10.1371/journal.pone.0359960
UR - https://doi.org/10.1371/journal.pone.0359960
AB - Clinical evidence supports the safety and efficacy of imeglimin, a new oral antidiabetic medication that increases insulin secretion and reduces insulin resistance. However, comparative real-world safety data with dipeptidyl peptidase-4 inhibitors, widely used in Japan, remain limited. This retrospective, pharmacy-based cohort study compared the incidence of adverse events (gastrointestinal events and hypoglycemia) among patients newly prescribed imeglimin or sitagliptin in real-world settings. Using a new-user design, we analyzed the 2022–2024 community pharmacy data across Japan, including 1,140 and 990 new imeglimin and sitagliptin users, respectively. Primary outcome (incidence of treatment-related events classified using Medical Dictionary for Regulatory Activities terminology) was evaluated using Cox proportional hazards models. Unadjusted and multivariable-adjusted hazard ratios (aHRs) for events during a 4-month follow-up were estimated. At least one adverse event was reported among 31% of imeglimin users versus 22% of sitagliptin users. Hypoglycemia risk differed non-significantly between groups (aHR: 0.66; 95% confidence interval [CI]: 0.20–2.22). However, imeglimin was associated with substantially higher risks of gastrointestinal events than sitagliptin (aHR: 5.44; 95% CI: 3.44–8.61), particularly nausea (aHR: 15.34; 95% CI: 3.50–67.23), diarrhea (aHR: 7.90; 95% CI: 2.54–24.62), and abdominal discomfort (aHR: 6.02; 95% CI: 1.47–24.58). Sensitivity analyses in patients receiving monotherapy yielded increased risk (hazard ratio (HR): 5.36; 95% CI: 2.63–10.92). Imeglimin use was associated with a higher incidence of gastrointestinal events than sitagliptin in Japanese clinical practice, closely approaching our prespecified threshold for clinical significance. Conversely, no significant difference was observed in hypoglycemia risk, although this finding should be interpreted with caution owing to the limited number of events. Involving community pharmacists allowed for active monitoring and identification of events that are often underreported in large-scale claims databases. Clinicians should prioritize gastrointestinal monitoring during initial stages of imeglimin therapy, particularly in older patients with complex treatment regimens.
SN - 1932-6203
ER -