Evaluation of Effects of Triple Therapy with Pioglitazone and Rosiglitazone Versus Dual Drug Therapy on Glycemic Control, Beta-cell Function, Lipid Profile and C-reactive Protein and the Cost-effectiveness in North Indian Rural Population

Prachi Arora1, Jatinder Singh2, B.S. Bal2. 1Quantum Solutions India, Chandigarh, Punjab, India, 2Government Medical college, Amritsar, Punjab, India.

Background: The role of insulin sensitisers in glycemic control as well as the effect on lipid profile is well known. These agents also have a promising role in improving beta-cell survival and thus function and also in decreasing cardiovascular risk markers.

Objectives: This study was designed to see the effectiveness and safety of add-on therapy with rosiglitazone and pioglitazone in combination with glibenclamide and metformin in uncontrolled type 2 diabetic patients. 75 patients uncontrolled on glibenclamide (5-15 mg)/metformin (500mg) for 6 months were recruited in this 24 weeks long randomized placebo controlled study. Divided into three groups of 25 patients each, add-on therapy was given with rosiglitazone (4 mg), pioglitazone (15 mg) and a placebo respectively. Levels of HbA1c, total cholesterol, triglycerides, HDL, LDL, fasting insulin, C-peptide and CRP levels were recorded and compared. Also the cost per unit change in fasting blood sugar for the three groups and the incremental cost effectiveness ratio (ICER) of using triple therapy to achieve the ADA targets for glycemic control was calculated.

Results: Addition of rosiglitazone & pioglitazone showed a significant decrease in HbA1c by 1% each and also a significant mean decrease in fasting blood sugar of 70.8 mg/dl and 57.3 mg/dl respectively. Treatment with rosiglitazone and pioglitazone showed an increase in mean levels of HDL by 6.0 mg/dl & 7.2 mg/dl, and a decrease in the levels of triglycerides by 43.5 mg/dl & 42.3 mg/dl, fasting plasma insulin by 9.0 mg/dl & 7.2 mg/dl, C-peptide by 0.5 mg/dl each and CRP levels by 0.13 mg/dl & 0.14 mg/dl respectively from the baseline. Rosiglitazone was associated with increased levels of total cholesterol by 31.4 mg/dl, LDL by 34.1 mg/dl & pioglitazone with a decrease in the mean levels of total cholesterol by 53.2 mg/dl, LDL by 52 mg/dl. The effects were statistically significant. No serious adverse effects occurred requiring discontinuation of therapy. The average cost per unit decrease in fasting blood sugar was INR 15.25, 20.41 and 13.98 ( GBP 0.19, 0.26, 0.17) respectively for the three groups [1 GBP = 80 INR]. The ICER for pioglitazone & rosiglitazone therapy compared to dual therapy was 16.57 & 22.94 for a period of six months respectively.

Conclusions: Use of these drugs in combination therapy should be individualized keeping in mind the differences and careful evaluation of the patient’s profile and the socioeconomic status.