The Improvement in Cardiovascular Risk Markers with Glimepiride in Pre-diabetic non-obese Subjects: Similar to Obese Cohort Treated with Metformin

Background: We recently documented better efficacy of glimepiride in non obese subjects for delaying progression from Pre diabetes to type 2 diabetes as compared to metformin in obese subjects over duration of 5-9 years (mean, 7.2±0.2). Metformin was the first-line therapeutic agent among newly diagnosed overweight patients with diabetes. Moreover, no deaths or adverse cardiovascular events occurred in either group and this finding may be attributed to beneficial changes in lipids and cardiovascular surrogate markers. However, the effects of interventions on lipids and cardiovascular surrogate markers were not reported.

Objective: Therefore, Cardiovascular risk factors including Lipid fractions, e.g. serum Total cholesterol (TC), Triglyceride (TG), Low density Lipoprotein cholesterol (LDLC), High Density Lipoprotein Cholesterol (HDLC) and other markers, e.g. Homocysteine (HomC), highly sensitive C-Reactive Protein (CRP), Fibrinogen (FIBR) and Plasminogen Activator Inhibitor1 (PAI1) were assessed prior to intervention and at interval of 6 months’ in subjects with Pre diabetes; lean treated with glimepiride and obese administered metformin.

Subjects and Methods: 18 non obese subjects, 10 men and 8 women ages 27-78 years and 20 obese subjects, 10 men and 10 women with ages 32-81 years with Pre diabetes (fasting plasma glucose, 100 – 125 mg/dl and/or HbA1c, 5.7-6.4%) participated in the study. The study period was 5-9 years (mean, 7.2 ± 0.2). Non obese subjects received glimepiride and obese subjects were administered metformin. Subjects were counseled with lifestyle intervention (appropriate diet and exercise) at each visit during the study. Comparisons were conducted between lipids and CV markers at entry, at six months and at the last visit of the study for individual group as well as between groups for levels at baseline and at the end of the study period.

Results: In glimepiride group, marked improvements occurred in all parameters following treatment (Post Rx) at 6 months and were sustained till the end of the study HbA1C (%): 6.2 ± 0.2, 5.5± 0.1*, 5.7 ± 0.1*; TC (mg/dl): 212± 15, 174 ± 13*,178 ± 14*; TG (mg/dl): 202± 32, 162± 28*, 178± 14*; LDLC: 130± 12, 105± 10*, 109± 9*; Non HDLC(mg/dl): 181 ± 24, 130 ± 14*,109± 9*; HomC (? Mol/l): 18± 3, 11± 2*, 12 ± 2*; CRP(Units): 13 ± 3, 6 ± 2*,5 ± 2*; FIBR (mg/dl): 403 ± 41, 296 ± 32*, 289± 28*; PAI1 (ng/ml): 18 ± 4, 13 ± 3*, 12 ± 4*; Post Rx vs. Pre Rx, p<0.05 for all values]. HDLC was not significantly altered. Similar changes were also noted in obese subjects treated with metformin. No significant differences were also noted between 2 groups at the entry, 6 months or the end of study.

Conclusion: In subjects with Pre diabetes, glimepiride is as effective in improving lipid profiles and cardiovascular surrogate markers in nonobese when compared with metformin in obese subjects thus explaining similar cardiovascular outcomes in both groups.