Comparison of glycaemic control over 1 year with pioglitazone or gliclazide in patients with Type 2 diabetes.
OBJECTIVE
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 HbA1c values. The 1-year changes in HbA1c, 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 HbA1c (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 micromol/kg/min, P = 0.042) than in the gliclazide group (-1.02 micromol/kg/min). A few, mild adverse events occurred in both groups.


CONCLUSIONS
A comparable decrease in HbA1c 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.
Perriello
G
G
Section of Internal Medicine, Endocrinology and Metabolism, Department of Internal Medicine, University of Perugia, Perugia, Italy. gabriele@dimisem.med.unipg.it
Pampanelli
S
S
Di Pietro
C
C
Brunetti
P
P
D001786:Blood Glucose / Q000187:drug effects*; D015190:Blood Glucose Self-Monitoring; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D005907:Gliclazide / Q000009:adverse effects / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008134:Long-Term Care; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*
D001786:Blood Glucose; D005907:Gliclazide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077205:Pioglitazone; D045162:Thiazolidinediones