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Clin Ther. 2002 Oct;24(10):1690-705.

Health and economic effects of adding nateglinide to metformin to achieve dual control of glycosylated hemoglobin and postprandial glucose levels in a model of type 2 diabetes mellitus.

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  • 1Caro Research Institute, Boston, Massachusetts, USA.



Type 2 diabetes mellitus is a common disease whose complications have great costs, both in quality of life and expense of treatment. Improving glycemic control, as measured by monitoring glycosylated hemoglobin (HbA1c) levels, can reduce the rate of such complications.


The aims of this study were to estimate the lifetime costs associated with diabetes-related complications in a theoretical population receiving metformin monotherapy and to predict the health and economic effect of improving glycemic control in this theoretical population by combining metformin with nateglinide.


A pharmacoeconomic model was developed to simulate the long-term (30 years) complication rates (microvascular and macrovascular) of a cohort of patients with type 2 diabetes mellitus. The model simulated each year of life for each patient in a theoretical cohort of 10,000 patients until diabetes-related complications were present or death occurred. The mean accumulated costs (direct medical costs for acute care and subsequent care for diabetes-related complications), mean survival time, and the frequency of each type of complication were estimated. Both effectiveness and cost data were discounted at 3%. Sensitivity analyses were conducted on key model input parameters.


Average costs of treating complications in theoretical patients undergoing metformin monotherapy were estimated at $29,565 per patient. Savings of $2,742 were estimated per patient for all complications--particularly, nephropathy ($1,166) and macrovascular disease ($632)--when nateglinide was added. The cost-effectiveness ratio of adding nateglinide to metformin was estimated at $27,131 per undiscounted life-year gained (95% CI, $23,710-$28,577) or $43,024 (95% CI, $37,285-$45,193) per additional discounted life-year gained. In the sensitivity analyses, decreasing HbA1c level at baseline, HbA1c upward drift, and duration of disease improved survival.


Combination therapy with nateglinide and metformin, compared with metformin alone, was predicted to reduce the frequency of complications and, thus, treatment costs in this theoretical model. The major factor in cost savings was fewer complications due to nephropathy. The increased drug treatment costs were expected to be offset by the long-term savings from reducing complication rates.

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