Comparative Study of the Efficacy of Ranolazine as Add-On Therapy With Metformin Versus Metformin Monotherapy on Glycaemic Control in Patients of Type 2 Diabetes Mellitus

BACKGROUND: Type 2 diabetes mellitus (T2DM), being a progressive metabolic disorder, often needs combination therapy for optimal glycaemic control. Metformin is the standard first-line agent, but its efficacy may diminish over time. Ranolazine, an antianginal drug with emerging antihyperglycaemic properties, has shown promise in improving glucose regulation. This study evaluated the efficacy of ranolazine as an add-on therapy to metformin compared with metformin monotherapy. METHODS: A quasi-experimental comparative study was conducted in a tertiary care hospital in eastern India. Adults aged 18-75 years with newly diagnosed or metformin-stabilised T2DM (HbA1c 6.5-9%) were enrolled. Group M received metformin 1000 mg once daily, while Group M+R received metformin 1000 mg once daily plus ranolazine (500 mg twice daily, up-titrated to 1000 mg twice daily). Follow-up of patients was conducted for six months, with assessments at baseline, three months, and six months. The primary endpoint was the mean reduction in HbA1c at three months, while secondary endpoints included changes in fasting blood glucose (FBG), post-prandial blood glucose (PPBG), and the need for rescue medication. RESULTS: Of 120 randomised patients, 54 in Group M and 58 in Group M+R completed the study. At three months, the combination group achieved a significantly greater HbA1c reduction (mean difference 0.25%, p=0.022), with sustained benefit at six months (mean difference 0.23%, p=0.037). FBG and PPBG were significantly lower in the combination group at both three and six months. Regression analysis identified longer diabetes duration, higher LDL, and elevated baseline HbA1c as predictors of HbA1c change. No increased risk of hypoglycaemia was observed. CONCLUSION: Ranolazine, when added to metformin, provides incremental and statistically significant improvements in glycaemic control, supporting its potential role as an adjunct therapy in T2DM. Larger, longer-term studies are warranted to confirm durability and cardiovascular benefits.