The Journal of the Association of Physicians of India最新文献

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.

Mineralocorticoid receptor antagonists (MRAs) are one of the guideline-directed medical therapies for patients with heart failure and chronic kidney disease due to their anti-inflammatory and antifibrotic effects. MRAs regulate mineralocorticoid receptor (MR) signaling by inhibiting aldosterone binding to MR. MRAs are classified into steroidal and nonsteroidal categories based on their molecular interactions and clinical applications. Steroidal MRAs have been widely used in clinical practice and have demonstrated significant efficacy. Continuous advancements in the field have led to the development of nonsteroidal MRAs with greater receptor selectivity and better safety profile.

Early initiation of guideline-directed medical therapies (GDMTs) in heart failure (HF) and their uptitration to the target dose confer mortality benefits and reduce the risk of readmission. GDMT nonuse is a significant predictor of mortality in HF patients. However, GDMT prescription and adherence in India are low. Of the GDMTs, mineralocorticoid receptor antagonists (MRAs) are the least prescribed. There are multilevel gaps [healthcare professional (HCP)-related, patient-related] in the adoption and use of MRAs in HF. There is an unmet need to identify these gaps and formulate mitigation strategies to close them. This can improve or enhance GDMT adoption in the HF treatment paradigm.

Clinical inertia is a major cause of mineralocorticoid receptor antagonist (MRA) underuse and failure to intensify MRA dose in heart failure (HF). Hyperkalemia and worsening of renal function are the main causes of clinical inertia seen with MRA. However, evidence shows that the risk of hyperkalemia is not very high with MRA use, and patients often die due to MRA withdrawal rather than hyperkalemia itself. Hence, addressing this fear of hyperkalemia is important to improve MRA prescription and patient outcomes. Other androgenic side effects of MRAs should also be managed for better adoption of this guideline-directed medical therapy in HF.

How to cite this article: Bansal S. Guest Editorial. J Assoc Physicians India 2026;74(1):6-6.

Mineralocorticoid receptor antagonists (MRAs) are important pillars in the treatment of heart failure (HF), chronic kidney disease (CKD), and diabetic kidney disease (DKD). MRAs share complementary pathways with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) in patients with cardiovascular-kidney-metabolic (CKM) syndrome. Combination therapies of MRA with SGLT2i and GLP-1RA are showing promising results in CKM than individual therapies. Further, the unique action of MRAs in antagonizing MR receptors and aldosterone, implicated in the pathophysiology of several conditions, is paving the way for clinical trials and promising results in these therapeutic areas. Disease-specific biomarkers such as UACR and eGFR are increasingly being used to individualize treatment with MRA. Utilizing MRA-specific biomarkers may open the path for precision medicine and further treatment individualization.