New research presented by Peter Weissman, M.D., from the University of Miami, at the 64th Annual Scientific Sessions of the American Diabetes Association shows that combination treatment with rosiglitazone maleate and metformin significantly improves certain markers of cardiovascular disease risk in patients with type 2 diabetes compared to metformin alone.
These data suggest that this combination of treatments provides certain cardiovascular benefits more effectively than metformin treatment alone. "Rosiglitazone has shown to be effective in improving glycemic control and reducing insulin resistance; now these new data show that the early addition of rosiglitazone to metformin monotherapy may offer other complementary and additive cardiovascular benefits in patients with type 2 diabetes," said Dr. Weissman, lead study author and associate clinical professor of Internal Medicine, University of Miami School of Medicine.
"These findings are important because cardiovascular disease is so prevalent and is the leading cause of diabetes-related deaths." Diabetes is a serious disease, which if not managed properly can cause debilitating and potentially life-threatening complications, such as cardiovascular disease. Cardiovascular disease is one of the most serious complications of diabetes and is attributed to 80 percent of diabetes-related deaths. Diabetes, in addition to smoking, high cholesterol levels and high blood pressure are all risk factors for cardiovascular disease.
Recent research shows that cardiovascular disease risk can also be assessed by "non-traditional" risk markers associated with the development of inflammation and atherosclerosis (the hardening of the arteries), including matrix metalloproteinase (MMP-9), plasminogen activator inhibitor-1 (PAI-1) and C-reactive protein (CRP) among others.
Combination Treatment Shows Potential Cardiovascular Benefits
These new data were from a sub-study of the EMPIRE clinical trial also presented at the American Diabetes Association Scientific Sessions. After 24 weeks of treatment, 90 patients in a sub-study were evaluated for changes in key cardiovascular biomarkers, including MMP-9, PAI-1 and CRP. This study compared two possible therapeutic strategies of uptitrating metformin monotherapy to a maximal level or adding rosiglitazone to a more moderate dose of metformin.
All study participants were initially treated with 500 mg twice daily of metformin for at least three weeks before being randomized in a blinded fashion to receive combination treatment with added rosiglitazone (2 mg bid, n=70) or an additional 500 mg of metformin (1500 mg daily dose, n=57, the uptitrated metformin group). After eight weeks, the doses were increased to a total daily dose of 8 mg of rosiglitazone plus 1 g of metformin or 2 g of metformin for an additional 16 weeks.
Treatment with rosiglitazone in combination with metformin resulted in positive improvements on known markers of cardiovascular disease risk beyond that of uptitrating metformin alone. Specifically, the rosiglitazone and metformin combination was found to have favorable treatment effects on MMP-9 [-29.92% (-46.21, -8.70) p=0.009] and PAI-1 [-32.38% (-51.36, -5.99) p=0.021], compared to uptitrating metformin monotherapy after 24 weeks.
The rosiglitazone plus metformin group demonstrated a significant reduction from baseline in CRP [-27.0% (-44.6, -3.8) p=0.026] compared to a non-significant reduction in CRP in the metformin uptitration group [-9.8% (- 38.1, 31.4) p=0.58]. The adverse events observed in the study were similar to those commonly seen with thiazolidinediones and metformin therapies, as described in the Avandia and metformin labels. "This study demonstrates the potential cardio-protective effects of combination therapy by adding a true insulin sensitizer, rosiglitazone, early to metformin therapy," said Dr. Weissman. "Since cardiovascular disease is such a common and dangerous complication of diabetes, using a treatment combination that can effectively manage blood sugar levels and offer potential cardiovascular benefits is extremely important."
Insulin Resistance, Diabetes and Cardiovascular Disease
Type 2 diabetes is characterized by high blood sugar levels that occur when the body cannot make enough insulin and/or is unable to respond normally to the insulin it already makes, a condition called insulin resistance.