The primary results of our study show first, that metformin monotherapy provided durable glycemic control in only half the participants; second, that the combination of metformin and rosiglitazone improved the durability of glycemic control; and third, that metformin combined with lifestyle intervention was no better than metformin alone in maintaining glycemic control. The differential effect among treatments did not appear to be due to differences in adherence and could not be explained by baseline characteristics, differential effects on BMI, or treatment-group differences in insulin secretion, insulin sensitivity, or body composition.
The rate of treatment failure with metformin monotherapy was higher in this cohort than in similar cohorts of adults treated with metformin,13-15 although the definition of failure differed among the studies. The reason for the decreased durability of glycemic control with metformin is unclear but is unlikely to be due to poor medication adherence, since adherence was more than 80% during the first year of the study, when half the patients had treatment failure, and there was no significant difference in the rate of loss of glycemic control between participants who adhered to the medication regimen and those who did not. Further analysis is required to determine whether the apparent decrease in the durability of glycemic control with metformin in adolescents as compared with adults reflects biologic differences, pathophysiological differences, or both.The combination of rosiglitazone and metformin reduced the rate of treatment failure as compared with metformin monotherapy, despite a small increase in BMI and fat mass in the rosiglitazone-treated participants. Whether the effect shown in this study is specific for rosiglitazone, a more general effect of thiazolidinediones, or a feature of combination therapy is unclear. This question is of particular importance, given the currently restricted status of rosiglitazone in the United States and Europe. The absence of adverse events related to rosiglitazone, including the absence of an identified effect of rosiglitazone on bone density in this cohort of children and adolescents, an age group characterized by skeletal growth, should be interpreted cautiously, given the limited sample size.The lifestyle program developed for the study was a multicomponent intervention based on the best available evidence, individually delivered by trained personnel, and with good participant adherence to visits. Although metformin plus lifestyle intervention significantly decreased percent overweight, this did not translate into sustained glycemic control, as compared with metformin monotherapy. Further analysis of the effect of various components of the lifestyle intervention is needed to understand the current findings and identify ways to effectively integrate behavioral self-management in the ongoing care of youth with type 2 diabetes.
The primary results of our study show first, that metformin monotherapy provided durable glycemic control in only half the participants; second, that the combination of metformin and rosiglitazone improved the durability of glycemic control; and third, that metformin combined with lifestyle intervention was no better than metformin alone in maintaining glycemic control. The differential effect among treatments did not appear to be due to differences in adherence and could not be explained by baseline characteristics, differential effects on BMI, or treatment-group differences in insulin secretion, insulin sensitivity, or body composition.The rate of treatment failure with metformin monotherapy was higher in this cohort than in similar cohorts of adults treated with metformin,13-15 although the definition of failure differed among the studies. The reason for the decreased durability of glycemic control with metformin is unclear but is unlikely to be due to poor medication adherence, since adherence was more than 80% during the first year of the study, when half the patients had treatment failure, and there was no significant difference in the rate of loss of glycemic control between participants who adhered to the medication regimen and those who did not. Further analysis is required to determine whether the apparent decrease in the durability of glycemic control with metformin in adolescents as compared with adults reflects biologic differences, pathophysiological differences, or both.The combination of rosiglitazone and metformin reduced the rate of treatment failure as compared with metformin monotherapy, despite a small increase in BMI and fat mass in the rosiglitazone-treated participants. Whether the effect shown in this study is specific for rosiglitazone, a more general effect of thiazolidinediones, or a feature of combination therapy is unclear. This question is of particular importance, given the currently restricted status of rosiglitazone in the United States and Europe. The absence of adverse events related to rosiglitazone, including the absence of an identified effect of rosiglitazone on bone density in this cohort of children and adolescents, an age group characterized by skeletal growth, should be interpreted cautiously, given the limited sample size.The lifestyle program developed for the study was a multicomponent intervention based on the best available evidence, individually delivered by trained personnel, and with good participant adherence to visits. Although metformin plus lifestyle intervention significantly decreased percent overweight, this did not translate into sustained glycemic control, as compared with metformin monotherapy. Further analysis of the effect of various components of the lifestyle intervention is needed to understand the current findings and identify ways to effectively integrate behavioral self-management in the ongoing care of youth with type 2 diabetes.
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The primary results of our study show first, that metformin monotherapy provided durable glycemic control in only half the participants; second, that the combination of metformin and rosiglitazone improved the durability of glycemic control; and third, that metformin combined with lifestyle intervention was no better than metformin alone in maintaining glycemic control. The differential effect among treatments did not appear to be due to differences in adherence and could not be explained by baseline characteristics, differential effects on BMI, or treatment-group differences in insulin secretion, insulin sensitivity, or body composition.
The rate of treatment failure with metformin monotherapy was higher in this cohort than in similar cohorts of adults treated with metformin,13-15 although the definition of failure differed among the studies. The reason for the decreased durability of glycemic control with metformin is unclear but is unlikely to be due to poor medication adherence, since adherence was more than 80% during the first year of the study, when half the patients had treatment failure, and there was no significant difference in the rate of loss of glycemic control between participants who adhered to the medication regimen and those who did not. Further analysis is required to determine whether the apparent decrease in the durability of glycemic control with metformin in adolescents as compared with adults reflects biologic differences, pathophysiological differences, or both.The combination of rosiglitazone and metformin reduced the rate of treatment failure as compared with metformin monotherapy, despite a small increase in BMI and fat mass in the rosiglitazone-treated participants. Whether the effect shown in this study is specific for rosiglitazone, a more general effect of thiazolidinediones, or a feature of combination therapy is unclear. This question is of particular importance, given the currently restricted status of rosiglitazone in the United States and Europe. The absence of adverse events related to rosiglitazone, including the absence of an identified effect of rosiglitazone on bone density in this cohort of children and adolescents, an age group characterized by skeletal growth, should be interpreted cautiously, given the limited sample size.The lifestyle program developed for the study was a multicomponent intervention based on the best available evidence, individually delivered by trained personnel, and with good participant adherence to visits. Although metformin plus lifestyle intervention significantly decreased percent overweight, this did not translate into sustained glycemic control, as compared with metformin monotherapy. Further analysis of the effect of various components of the lifestyle intervention is needed to understand the current findings and identify ways to effectively integrate behavioral self-management in the ongoing care of youth with type 2 diabetes.
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