Background: Pioglitazone as monotherapy and in combination with sulfonylurea, metformin, or insulin has consistently demonstrated improved glycaemic and lipid parameters in patients with type 2 diabetes mellitus.
Objective: We performed a subanalysis to examine the effect of pioglitazone on glycaemia and lipids in patients <65 and > or =65 years of age in two double-blind, placebo-controlled monotherapy studies and in three separate multi-centre trials.
Method: In Study 1, 197 patients were randomised to receive pioglitazone 30 mg/day or placebo for 16 weeks. Study 2 was a forced dose-titration trial in patients randomised to receive pioglitazone 7.5/15/30 mg/day, pioglitazone 15/30/45 mg/day, or placebo daily for 26 weeks. Each of the lower dosages was given for at least 4 weeks and the highest dosage for 16 weeks. The three combination studies evaluated efficacy of pioglitazone 30 or 45 mg/day over a 24-week period in combination with sulfonylureas, metformin, or insulin.
Results: In both placebo-controlled monotherapy studies, at 16 weeks, and at maximum pioglitazone dosage, 0.53-0.55% and 0.57-1.27% mean reductions from baseline in glycosylated haemoglobin (HbA(1c)) were seen in patients aged <65 (n = 225) and > or =65 (n = 45) years, respectively. There were statistically significant differences between the placebo and pioglitazone groups in each age cohort. Similar effects were observed in fasting plasma glucose (FPG) levels, with 2.03-2.59 mmol/L and 3.20-4.44 mmol/L mean reductions from baseline, respectively, which were significantly different from the changes in the placebo group, but there was no difference between pioglitazone groups. At treatment endpoint in combination trials, pioglitazone added to sulfonylurea produced a mean decrease in HbA(1c) of 0.78-1.61%, and 1.64-1.96% in patients aged <65 (n = 557) and > or =65 (n = 115) years, respectively. Pioglitazone added to metformin produced a mean decrease in HbA(1c) of 0.78-1.03% and 0.78-0.98% in patients aged <65 (n = 686) and > or =65 (n = 112) years, respectively. Pioglitazone added to insulin produced a mean decrease in HbA(1c) of 1.13-1.37% and 1.39-1.66% in patients aged <65 (n = 500) and > or =65 (n = 156) years, respectively. In patients aged > or =65 years, hypoglycaemia was observed in 1 of 14 patients and in 0 of 13 patients in the two monotherapy studies. In the combination studies, the incidence of hypoglycaemia among patients aged > or =65 years was as follows: 26.7-28.8% combined with sulfonylurea; 0-4.4% combined with metformin; and 53.4-56.4% combined with insulin.
Conclusion: Pioglitazone monotherapy, or added to a sulfonylurea, metformin, or insulin demonstrated no significant differences in effectiveness while exhibiting similar adverse events in patients aged > or =65 years compared with patients aged <65 years. Well-controlled randomised clinical trials are recommended to confirm the impact of pioglitazone therapy on the glycaemic and lipid control in elderly patients with type 2 diabetes.