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Pioglitazone or ramipril plus intensive insulin therapy improved vascular dysfunction
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Patients with type 2 diabetes may have another therapeutic option to improve vascular dysfunction and markers of inflammation.
When added to intensive insulin therapy, pioglitazone (Actos, Takeda) enhanced endothelial-mediated vasodilation, decreased fatty acids and triglycerides and increased plasma adiponectin. Adding of ramipril to insulin therapy led to enhanced endothelial-independent vasodilation and reduced endothelin-1.
Of 30 participants, 12 received continuous subcutaneous insulin infusion and 18 received multiple daily injections. The researchers randomly assigned participants to pioglitazone 45 mg/day, ramipril 10 mg/day or placebo for 36 weeks. The researchers found that each of the three therapies was associated with similar decreases in fasting plasma glucose and HbA1c.
Furthermore, pioglitazone was associated with a greater increase in forearm blood flow during reactive hyperemia and acetylcholine. Ramipril produced greater forearm blood flow during treatment with nitroprusside. – by Katie Kalvaitis
Diabetes Care. 2008;31:121-127.
This study is interesting in that it takes a broad view of diabetes as a condition of impaired vascular health and considers frequently used treatments for their effects on vascular function. The results are interesting in that both pioglitazone and ramipril have measurable, albeit independent, effects to improve forearm blood flow. Interestingly, insulin treatment alone also seems to be beneficial. These results are compatible with current trends in diabetes care that emphasize earlier and more intensive use of insulin, combination treatment including oral agents like thiazolidinediones and a favored status for angiotensin-converting enzyme inhibitors to treat hypertension in diabetes. On the other hand, this was a small study with surrogate endpoints for cardiovascular benefits. The results with ramipril are in keeping with the results of the HOPE trial that showed a reduction in cardiovascular outcomes in treated diabetic subjects. The case for pioglitazone is less clear since the results of the PROACTIVE trial were not clear. The major message for practicing physicians is that approaches to preventive cardiology for diabetic patients continues to develop and that this is likely to be a beneficial clinical strategy.
– David D’Alessio, MD
Director, Division of Endocrinology, University of Cincinnati