# Imeglimin may affect hemoglobin A1c accuracy via prolongation of erythrocyte lifespan in patients with type 2 diabetes mellitus: insights from the INFINITY clinical trial

## TL;DR

Imeglimin, a diabetes drug, may cause HbA1c levels to appear higher than actual blood sugar levels by extending red blood cell lifespan, suggesting alternative markers like GA and 1,5-AG may be more accurate.

## Contribution

This study is the first to show that imeglimin may prolong erythrocyte lifespan, affecting HbA1c accuracy in type 2 diabetes patients.

## Key findings

- HbA1c decreased gradually, while GA and 1,5-AG showed faster changes after imeglimin treatment.
- Erythrocyte lifespan was significantly prolonged during the treatment period.
- HbA1c may underestimate early glycemic effects of imeglimin compared to other markers.

## Abstract

Imeglimin is a novel type 2 diabetes (T2D) drug that is expected to improve mitochondrial function. In phase 3 trials, imeglimin demonstrated a gradual reduction in hemoglobin A1c (HbA1c), with a plateau at approximately 20–24 weeks. As erythrocyte lifespan may affect HbA1c accuracy, this clinical trial aimed to evaluate the potential discordance between HbA1c and other glycemic markers following imeglimin therapy and to explore whether imeglimin affects erythrocytes.

This was a prospective, single-arm, open-label exploratory clinical trial (INFINITY study) conducted at Naka Kinen Clinic, Japan. Twenty-nine Japanese patients with inadequately controlled T2D received imeglimin 2,000 mg/day for six months. The primary endpoint was the change in hemoglobin concentration from baseline to Month 6. Secondary endpoints included serial changes in HbA1c, glycoalbumin (GA), 1,5-anhydroglucitol (1,5-AG), and erythrocyte lifespan, as well as comparison of glycemic reduction rates across these markers.

The change in hemoglobin concentration at 6 months was not statistically significant (mean ± SD: −0.2 ± 0.9 g/dL; p = 0.23). While HbA1c and GA decreased and 1,5-AG increased one month after imeglimin initiation, GA and 1,5-AG showed rapid changes compared to the gradual decrease in HbA1c. The divergence in reduction rates between HbA1c and the other markers persisted for up to two months. When erythrocyte lifespan was assessed using 3-month interval averages, significant prolongation was observed in both the 1–3 month and 4–6 month periods compared to the pre-treatment period (−2 to 0 months).

This exploratory clinical trial suggests that imeglimin may prolong erythrocyte lifespan, resulting in disproportionately elevated HbA1c levels relative to true glycemic status. Reliance on HbA1c alone may underestimate imeglimin’s early glycemic effects, highlighting the value of alternative markers such as GA and 1,5-AG.

https://jrct.mhlw.go.jp/latest-detail/jRCTs031220489, Identifier jRCTs031220489.