Adiponectin and ADMA Level in Type-2 Diabetes Patients After 12 Weeks of Treatment with Glimepiride and Metformin Fixed Dose Combination (DIAGRAM Study)

Background: Recent published study on glimepiride showed remarkable increase of plasma adiponectin while metformin was associated with a decrease in asymmetric dimethylarginine concentrations. A fixeddose combination of glimepiride and metformin available in Indonesia with limited local data on plasma hba1c adiponectin and asymmetric dimethylarginine concentrations. Objective: This clinical trial aimed to evaluate the effect of fixed-dose combination of 1 mg glimepiride and 250 mg metformin Immediate Release on the level of plasma adiponectin, circulating asymmetric dimethylarginine, ankle-brachial pulse wave velocity, as well as fasting blood glucose and hba1c change in 40 patients with type 2 diabetes mellitus after 12 weeks of therapy. Methods: Diagram was an open label study. We compared pre- and post-treatment values of high molecular weight adiponectin and asymmetric dimethylarginine level after 12 weeks treatment period with fixeddose combination glimepiride/metformin. Forty patients with type 2 diabetes mellitus aged 40 – 60 years who were not currently treated with any Oral Anti Diabetic agents, statins, angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers for at least 8 weeks and the hba1c value between 7% and <10% have been enrolled for this clinical trial. Results: Fixed Dose Combination glimepiride/metformin is proven effective for treating forty patients with type-2 diabetes who were included in this study, even though plasma adiponectin was not significantly increased (34 ng/mL; p=0.201) by the administration of this fixed-dose combination for a 12 weeks treatment period as expected, however the treatment effect in increased adiponectin was shown in subjects with adiponectin dysfunction. Significant increase of asymmetric dimethylarginine median value (0.14 μmol/L, p<0.001) and decrease of ankle-brachial pulse wave velocity (-110.4 cm/sec, p=0.016) were shown in this study accompanied by the decrease in hba1c from 8.52% to 7.38% (p<0.001) and fasting blood glucose from 165.9 mg/dL to 123.1 mg/dL (p<0.001). Mild adverse events were reported in 7.5% patients, while serious adverse event was reported in one subject and was not related to study drug. Conclusion: It can be concluded that treatment with fixed-dose combination glimepiride/metformin has effect in improving endothelial function by increasing adiponectin and lowering ankle-brachial pulse wave velocity level significantly. Meanwhile, the administration of fixed-dose combination glimepiride/metformin may not have effect in decreasing ADMA level. Further studies which included larger population with more varied parameters are needed to confirm the relationship of this fixed-dose combination with other factors.