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- May 17, 2008 |
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"What are the optimal combination strategies in order to achieve glycaemic control?"Dr. Lawrence A. Leiter (biography)
English - 2003-08-26 - 27 minutes
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Summary :
Current guidelines for the management of type 2 diabetes emphasize the importance of optimal glycaemia in an attempt to reduce the risk of complications. Given the inadequacy of conventional monotherapies in maintaining blood glucose targets in the long term, new approaches to treating type 2 diabetes are required. In particular, earlier introduction of combination therapy is being increasingly recommended over conventional stepwise strategies.
Combinations of traditional oral therapies can provide effective glycaemic control for some patients. However, they are associated with drawbacks, for example over one-third of patients on metformin/glibenclamide report hypoglycaemic events. Similarly, while insulin is an effective add-on therapy, its use may be limited by hypoglycaemia and compliance issues associated with injection. In addition, some patients cannot tolerate traditional therapies at their maximal effective doses. This has created the need for new oral combination strategies that help patients to achieve and sustain glycaemic goals.
The thiazolidinediones (TZDs) are a class of oral anti-diabetic agents that reduce hyperglycaemia by directly targeting insulin resistance. In monotherapy, TZDs significantly lower HbA1c, fasting plasma glucose and post-prandial glucose, with rosiglitazone-mediated reductions in HbA1c demonstrated for up to 3 years to date. The complementary mode of action of the TZDs to both metformin and sulphonylureas, which primarily reduce hepatic glucose output and increase pancreatic insulin secretion, respectively, also make them ideal candidates for use in combination. For example, in patients inadequately controlled on metformin monotherapy, the addition of rosiglitazone provides an extra HbA1c lowering of up to 1.2% (up to 1.7% in patients with baseline HbA1c > 9%), compared to metformin alone. Long-term studies indicate that improvements in glycaemic control are sustained for at least 2.5 years. Importantly, three-fold more patients reach ADA treatment goals of <7% HbA1c compared with metformin monotherapy. Combination therapy with TZDs may also have benefits over increasing the dose of traditional monotherapies. For example, adding rosiglitazone to submaximal dose metformin significantly improves glycaemic control and reduces gastrointestinal adverse events compared with maximal dose metformin. Furthermore, rosiglitazone added to half-maximal dose of sulphonyureas provides significantly greater reduction in HbA1c compared with uptitrating the sulphonyurea dose (-1.3% compared with uptitrated sulphonyurea). Also, preliminary data concerning triple therapy with sulphonylurea, metformin and a TZD suggest that this may be a viable future strategy for patients with type 2 diabetes.
Thus, a greater and earlier use of combination therapy, particularly with glitazones, represents a rational approach to better achieve and maintain glycaemic goals and improve patient outcomes.
Learning objectives :
The participant will review new evidence about optimal combination strategies for achieving optimal glucose control.
Conclusions:
- Despite increasingly aggressive glycaemic targets, many persons with DM are still are still not achieving target.
- Although the cause of this is multifactorial, rigid adherence to a stepwise approach has led to significant delays in reaching targets.
- Combination therapy has been shown to improve glycaemic control and increase the proportion of patients achieving goals.
- Outcome studies with combination therapy are underway.
Bibliographic references :
Kipnes MS, Krosnick A, Rendell MS, Egan JW, Mathisen AL, Schneider RL. Pioglitazone hydrochloride in combination with sulfonylurea therapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, placebo-controlled study. Am J Med. 2001 Jul;111(1):10-7.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
Fonseca V, Rosenstock J, Patwardhan R, Salzman A. Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial. JAMA. 2000 Apr 5;283(13):1695-702.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi
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