Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with Type 2 diabetes

Aims  To compare long-term (1 year) efficacy and safety of pioglitazone and gliclazide in patients with Type 2 diabetes.

Methods  This was a double-blind, multicentre, comparative, parallel group trial in 283 patients with Type 2 diabetes, who were randomized to receive 1-year treatment with pioglitazone 30–45 mg/day or gliclazide 80–320 mg/day. Drug dose was titrated on the basis of self-monitored blood glucose (SMBG) measurements and HbA_1c values. The 1-year changes in HbA_1c, fasting blood glucose (FBG), insulin, HOMA-S (HOmeostatic Model Assessment) and SMBG were compared. In a subgroup of patients (n = 10), systemic glucose production and utilization were determined by a combination of isotopic (deuterated glucose) and clamp techniques.

Results  In both groups, there were similar decreases in HbA_1c (pioglitazone: −0.79%; gliclazide: −0.79%) and FBG (pioglitazone: −1.0 mmol/l; gliclazide: −0.7 mmol/l), whereas the slope of the reduction of fasting blood glucose was different between groups (P = 0.004). Insulin levels as well as insulin resistance assessed using HOMA-S decreased significantly only after pioglitazone treatment (−11.94 pmol/l and −1.03, respectively, both P = 0.002 vs. baseline). A significantly greater reduction in systemic glucose production was observed in the pioglitazone group (−2.48 µmol/kg/min, P = 0.042) than in the gliclazide group (−1.02 µmol/kg/min). A few, mild adverse events occurred in both groups.

Conclusions  A comparable decrease in HbA_1c and FBG was observed with pioglitazone and gliclazide. However, with pioglitazone there was a continuous decrease in FBG over 1 year, whereas gliclazide failed to maintain a similar trend. This favourable effect of pioglitazone was due to its insulin-sensitizing effect and ability to decrease systemic glucose production.