Diabetes mellitus is a serious disease characterized by an increase in blood glucose. It is estimated that more than one million Canadians over 12 years of age suffer from this condition. Type 2 diabetes is the most common form and affects 90% of persons with diabetes. Serious long-term complications can develop that affect the eyes, kidneys, nerves and blood vessels.
Rosiglitazone and pioglitazone are members of the newest class of oral anti-diabetic drugs called thiazolidinediones. Troglitazone, the first thiazolidinedione derivative developed, was removed from the US market in 2000 because of concerns with liver toxicity.
Thiazolidinediones decrease blood glucose levels through a new mechanism of action and appear to address insulin resistance, a key problem in type 2 diabetes. However, they are significantly more costly than existing drugs and patients must be monitored for liver problems. Therefore, there is a need to compare the efficacy and safety of these drugs with other anti-diabetic drugs.
To evaluate the evidence that compares rosiglitazone or pioglitazone with other oral anti-diabetic agents (including insulin), either when used alone or when added to a non-thiazolidionedione agent in the treatment of type 2 diabetes.
To determine the impact of listing thiazolidinediones on the budget of provincial drug plans in Canada.
In this systematic review, only randomized controlled trials comparing the efficacy of rosiglitazone or pioglitazone with other anti-diabetic agents were selected from a broad literature search. Primary outcome measures were fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c). A total of 19 relevant trials were found, 11 rosiglitazone and eight pioglitazone trials. The observation period for most studies was 52 weeks or less.
A budget impact analysis was used to determine the impact of listing rosiglitazone and pioglitazone on the formularies of publicly-funded drug plans in Canada.
When used alone, both rosiglitazone and pioglitazone have effects similar to comparator drugs on HbA1c and FPG, based on the findings from a small number of comparative trials.
When added to another anti-diabetic agent, the effect on HbA1c and FPG is significantly greater than continuing therapy with the other anti-diabetic agent alone. This is consistent with the work of others that shows combining two anti-diabetic agents provides a greater effect than using one alone.
Both drugs were generally well tolerated during the trials reviewed; only a few cases of heart failure and severe hypoglycemia (when added to another agent) were reported. No liver toxicity was observed. Long-term trials are required to evaluate their effect on the development of diabetic complications and long-term safety.
Based on the budget impact analysis, it is estimated that by 2004, if rosiglitazone and pioglitazone receive formulary listing throughout Canada, the net expenditure for the publicly-funded drug programs would increase nationally between $11.8 and $88.5 million per year, depending upon their utilization and the number of patients treated.