A Prospective Real-world Study to Assess Safety, Tolerability, and Effectiveness of Imeglimin among People with Type 2 Diabetes Mellitus Who are Intolerant to Metformin (PRISM Study).

Abstract

Background: Metformin has been the cornerstone of type 2 diabetes mellitus (T2D) pharmacologic management, but gastrointestinal (GI) intolerance limits its use in a significant subset of patients. In India, alternative therapies for metformin-intolerant subjects are needed given the high diabetes burden and early disease onset. Imeglimin, a novel oral antidiabetic agent with a distinct mitochondrial mechanism of action, has shown efficacy and tolerability but lacks large real-world evidence in Indian subjects unable to tolerate metformin.

Materials and methods: This 6-month, prospective, multicenter, observational study was conducted across 19 clinical sites in India to evaluate the effectiveness and safety of imeglimin in a real-world setting. The study population comprised adult patients with T2D who were identified as intolerant to metformin. Following enrollment, subjects were initiated on treatment with imeglimin, administered either as monotherapy or as add-on therapy to existing regimens. The primary effectiveness endpoint was the change from baseline in glycated hemoglobin (HbA1c) at 6 months and the assessment of safety and tolerability.

Results: Among the 722 analyzed subjects, the mean age was 53.1 years, and the mean baseline HbA1c was 8.5%. Imeglimin therapy produced sustained improvements: Mean HbA1c decreased by 1.26% at 6 months (p < 0.001). Imeglimin performed well as both monotherapy (reduction of 0.77% at 6 months, p < 0.001) and combination therapy [with two oral antidiabetic drugs (OADs), a reduction of 1.15%, p < 0.001; and with three or more OADs, a reduction of 1.86%, p < 0.001]. The treatment was well tolerated, with no serious adverse events reported. Overall, 29.7% of participants experienced side effects, most commonly GI symptoms (15.3%), followed by urinary or genital tract infections (5.0%), nausea or vomiting (5.1%), headache (7.1%), and hypoglycemia (1.1%).

Conclusion: Imeglimin demonstrates clinically meaningful glycemic efficacy in a real-world setting among metformin-intolerant patients. Its high efficacy, even in complex combination regimens, combined with a favorable safety profile and a low risk of hypoglycemia, establishes imeglimin as a highly valuable and effective alternative for patients who cannot tolerate metformin.