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- November 20, 2008 |
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"The Progressive Nature of Type 2 Diabetes - Update on Clinical Management: Results of the ADOPT Trial"Prof. Giancarlo Viberti (biography)
English - 2006-12-04 - 43 minutes
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Summary :
Clinical management of type 2 diabetes has conventionally relied on a stepwise approach, in which therapy is intensified, from diet and exercise, through monotherapy and then on to combination therapy, in response to steadily worsening glycaemic control. As such, the stepwise approach implicitly acknowledges type 2 diabetes as an inevitably progressive disorder and principally aims to respond to – rather than prevent – disease progression.
The benefits of intensive management to achieve good glycaemic control in reducing the risk of diabetic complications is now well established and was definitively demonstrated in the United Kingdom Prospective Diabetes Study (UKPDS). However, the UKPDS also showed that traditional antidiabetic agents including sulphonylureas, metformin and insulin do not maintain these improvements. Despite initial reductions in blood glucose levels when these agents were introduced as monotherapy, loss of glycaemic control then progressed at a similar rate as before pharmacotherapy. Loss of glycaemic control in the UKPDS correlated with declining pancreatic β-cell function which, with insulin resistance, underlies the development and progression of type 2 diabetes.
Since the UKPDS, a new class of antidiabetic agents, the thiazolidinediones (TZDs), have augmented the treatment options available in type 2 diabetes. The TZDs act by reducing insulin resistance and have also been shown to have protective effects on β-cells. Given their effects on the two pathological defects underlying type 2 diabetes, there has been considerable interest in the potential for TZDs to slow disease progression.
A Diabetes Outcome Progression Trial (ADOPT) will provide the largest assessment since the UKPDS of the major tools currently available to physicians regarding their ability to provide long-term glycaemic control and their potential to affect disease progression. In the study, treatment with the TZD rosiglitazone has been compared with glyburide or metformin in terms of the time to monotherapy failure (defined as fasting plasma glucose >10 mmol/l while on maximal effective or tolerated dose), and more than 3,500 participants with newly diagnosed diabetes have been followed over 4 years of treatment.
In addition to providing a crucial update on existing therapies, ADOPT also reminds us that progressive loss of glycaemic control is still a key challenge for physicians. Clinical management has evolved somewhat since the UKPDS. For example, earlier introduction of combination therapy is increasingly advocated in order to rapidly get people to their glycaemic targets and then keep them there as long as possible, given that individuals often experience extended periods of high blood glucose levels before therapy is intensified. Among the choice of possible combinations that are available today, that of a TZD with metformin may offer particular benefits in combining positive effects on the disease mechanisms underlying diabetes with proven cardiovascular benefits, whilst combination of a TZD with a sulphonylurea provides an effective alternative in patients intolerant to metformin.
Learning objectives :
After viewing this presentation the participant will be able to discuss:
Newly-released results from the ADOPT trial - Effects of rosiglitazone versus metformin or glyburide as initial therapy in recently diagnosed type 2 diabetic patients:
- Primary outcome: Time to monotherapy failure - FPG > 180 mg/dl (> 10 mmol/L)
- Secondary outcomes: FPG > 140 mg/dl (> 7.8 mmol/L); Changes in FPG, HbA1c, insulin sensitivity and beta-cell function
- Adverse events
- Clinical implications
Bibliographic references :
Steven E. Kahn, Steven M. Haffner, Mark A. Heise, William H. Herman, Rury R. Holman, Nigel P. Jones, Barbara G. Kravitz, John M. Lachin, M. Colleen O'Neill, Bernard Zinman, Giancarlo Viberti, for the ADOPT Study Group Glycemic Durability of Rosiglitazone, Metformin, or Glyburide Monotherapy NEJM. 2006 Dec;(23) 355:2427-2443
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