Positive results are dependent upon BMI at start of therapy This 24-week, double-blind, randomized study performed in 11 countries was designed as a head-to-head comparison of the efficacy and tolerability of vildagliptin and rosiglitazone as monotherapy in drug-naive type 2 diabetes patients. Seven hundred eighty-six adult subjects (age 18-80 years) with glycated hemoglobin (A1C) levels in the range of 7.5% to 11.0% and who did not have cardiovascular disease, congestive heart failure, liver disease, or various laboratory abnormalities were randomized on a 2:1 ratio to 100 mg vildagliptin (n = 519) or 8 mg rosiglitazone (n = 267), and were assessed at weeks 4, 12, 16, and 24 of active treatment. Analyzed on an intent-to-treat basis, the primary efficacy variable was change from baseline A1C after 24 weeks. Secondary variables were changes in fasting glucose, fasting lipids, and body weight.
A1C improved by -1.1% among vildagliptin users and -1.3% among rosiglitazone users, meeting the statistical criterion for noninferiority. It is interesting that a stratified analysis showed that greater A1C reductions among the vildagliptin group were achieved by those with body mass index (BMI) < 30 kg/m2, whereas rosiglitazone appeared more efficacious in patients with BMI ≥ 30 kg/m2. Fasting glucose levels decreased more with rosiglitazone compared with vildagliptin, and high-density lipoprotein increases also favored rosiglitazone. However, body weight increased by 1.6 kg among rosiglitazone-treated patients, but did not change in the vildagliptin group. In addition, compared with rosiglitazone, vildagliptin significantly decreased triglycerides as well as total and low-density lipoprotein cholesterol.
Vildagliptin is in the new dipeptidyl peptidase (DPP)-IV inhibitor class of antihyperglycemic drugs that increases alpha- and beta-cell responsiveness to glucose. Its apparent ability to reduce A1C without inducing weight gain makes it a promising new agent. The favorable lipid effects are also intriguing, and need further study. Rosiglitazone is a thiazolidinedione that targets insulin resistance by enhancing peripheral and hepatic insulin action. Although the end result is similar (reduction in A1C), the vastly different mechanistic actions of these 2 drugs likely explain some of the differences found in the secondary outcomes. In theory, the fact that vildagliptin worked best in subjects who were not obese suggests that this drug may be preferred when substantial beta-cell failure is the primary cause of hyperglycemia. On the other hand, rosiglitazone worked better in obese subjects and had a greater effect on fasting glucose, suggesting that it might be preferred in those with high insulin resistance. Such patients are often obese. Weight gain is never desirable; it may be of less concern in already obese patients, especially if body fat is being redistributed. In reality, beta-cell failure and insulin resistance usually coexist, and there is debate over which is the dominant cause of diabetes. The key point is that clinicians now have more options than ever to appropriately treat the variations of hyperglycemia that we singularly call type 2 diabetes.
Diabetes Care, (Volume 30, Number 2)
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