Actos May Improve Heart Safety
Actos, an insulin sensitizer in the glitazone class of type 2 oral diabetes medications, was found to reduce carotid artery intima-media thickness (IMT) as well as insulin resistance in a German study. Study participants were randomized to receive either Actos (pioglitazone) or Amaryl (glimepiride), an insulin secretagogue in the sulfonylurea class of type 2 oral diabetes medications, for 12 and 24 weeks. The study population consisted of 66 females and 107 males with an average age of 62.6 years, average BMI of 31.8 and average A1C of 7.5%.
After 24 weeks, only the Actos group saw reductions in carotid IMT. After 12 weeks, thickness decreased an average of 0.033 millimeters, and after 24 weeks the decrease reached an average of 0.054 millimeters. In addition, insulin resistance was significantly improved in the Actos group versus the Amaryl group.
Why is this study important to people with type 2 diabetes?
This study proves that lowering of glucose alone is not enough to reduce the risk for myocardial infarction. Type 2 diabetes is a very complex disease, and blood glucose deterioration is only one half of it. The lack of insulin effects at the inner layer of the blood vessels (that have nothing to do with glucose lowering) leads to this increased cardiovascular risk. To restore these effects, the treatment should focus on a reduction of insulin resistance. Basically this can be achieved by diet and exercise, but our study shows that Actos is a very potent drug not only in terms of glucose lowering but also in improving the situation in the blood vessels.
What else can type 2s do to improve their IMT?
Regular exercise and maintenance of a normal body weight is the best and cheapest way to reduce IMT. Next to Actos, the lipid-lowering drug class of statins has been shown to also have a beneficial effect on IMT. Preliminary results from a currently running study at our institute indicate that the combination of Actos with a statin shows a synergistic effect on cardiovascular risk markers, i.e., the combination seems to be better than the single drugs in this respect.
A new study published in today’s issue of Diabetes Care demonstrated that ACTOS improved components of diabetic dyslipidemia to a significantly greater extent than Avandia. Specifically, the results indicated that treatment with ACTOS lowered triglycerides (a type of lipid, or fat, found in food and the body), increased HDL-C (”good” cholesterol), and improved LDL-C (”bad” cholesterol) particle concentration and particle size. These differences were independent of blood glucose control and occurred without the use of a traditional lipid-lowering statin medication.
Diabetic dyslipidemia is a condition commonly found in people with type 2 diabetes and is an important risk factor for cardiovascular disease, the leading cause of death for people with type 2 diabetes. Diabetic dyslipidemia is characterized by increased triglycerides and decreased HDL-C. People with diabetic dyslipidemia also tend to have normal levels of LDL-C, but smaller, denser LDL-C particles that are likely to contribute to cholesterol build-up in arteries.
“This study provides important insight into the relative impact of each drug on important cardiovascular risk markers,” noted principal investigator Ronald B. Goldberg, M.D., professor of Medicine and Associate Director of the Diabetes Research Institute at the University of Miami Miller School of Medicine. “The results demonstrate a clear difference between ACTOS and Avandia on their effects on diabetic dyslipidemia, with ACTOS lowering triglycerides and raising HDL-C to a greater extent than Avandia.”
Study Design
This 24-week prospective, randomized, multicenter, double-blind clinical trial enrolled 802 people with type 2 diabetes (treated with diet alone or oral monotherapy) and dyslipidemia (not treated with any lipid-lowering medications).
Following a four-week “washout” period where patients discontinued their current diabetes medication and received a placebo, patients were randomized to receive either 30 mg of ACTOS(R) (pioglitazone HCl) once daily for 12 weeks followed by 45 mg of ACTOS once daily for the remainder of the study, or 4 mg of Avandia(R) (rosiglitazone maleate) once a day for 12 weeks followed by 4 mg of Avandia twice daily for the remainder of the study. These represent the maximally effective therapeutic doses for both medications.
“By eliminating other factors such as statins to control lipids and other medications to control blood glucose levels, we obtained a clear assessment of the blood sugar and lipid effects of both drugs,” added Dr. Goldberg.
Results
The study showed that blood glucose control, which was measured by A1C (a measure of blood glucose over a several-month period), was significantly improved in both ACTOS- and Avandia-treated patients with comparable changes from baseline. At baseline, average A1C scores were 7.6 percent in the ACTOS group and 7.5 percent in the Avandia group. Following treatment, average A1C was reduced by 0.7 percent and 0.6 percent respectively (P=NS), and mean A1C for both treatment groups was below the ADA goal of less than 7 percent.
Additionally, the study demonstrated that ACTOS and Avandia differed significantly in their effects on blood lipids:
* triglyceride levels decreased 12.0 percent in the ACTOS patients, and rose 14.9 percent in the Avandia patients (P<0.001).
* HDL-C rose 14.9 percent in the ACTOS patients, whereas it increased 7.8 percent in the Avandia patients (P<0.001).
* LDL-C particle concentration was reduced with ACTOS and increased with Avandia (P<0.001). LDL-C particle size increased more with ACTOS (P=0.005).
Total cholesterol (TC) and LDL-C increased with both drugs, but to a lesser extent with ACTOS. TC and LDL-C rose 15.9 and 23.3 percent, respectively, in the Avandia patients; they increased 5.7 percent and 15.7 percent, respectively, in the ACTOS patients (TC: P<0.001; LDL-C: P=0.002).
“Our knowledge regarding the association between type 2 diabetes and cardiovascular disease, which can be referred to as ‘CardioDiabetes,’ continues to grow,” said Robert Spanheimer, M.D., medical director for diabetes and metabolism at Takeda Pharmaceuticals North America. “Many factors can contribute to the increased risk of cardiovascular disease in people with diabetes, including multiple lipid abnormalities. It is important to understand the impact medications can have on individual lipid parameters. This study underscores the potential benefits of ACTOS beyond glycemic control in improving diabetic dyslipidemia in patients with type 2 diabetes. These findings require further research in order to determine whether the results reported here may affect cardiovascular risk.”
ACTOS(R) (pioglitazone HCl) Avandia(R) (rosiglitazone maleate) are insulin sensitizers belonging to the thiazolidinedione (TZD) class of oral anti-diabetes medications that have been approved by the Food and Drug Administration to improve blood glucose control in type 2 diabetes as an adjunct to diet and exercise.
About ACTOS
ACTOS works by directly targeting insulin resistance, a condition in which the body does not effectively use the insulin it produces to control blood glucose levels. ACTOS is taken once daily as an adjunct to diet and exercise, and is approved for use as monotherapy to lower blood glucose and in combination therapy with insulin, sulfonylureas or metformin.
Additional Information
ACTOS is not for everyone. ACTOS can cause fluid retention that may lead to or worsen heart failure, so tell your doctor if you have a history of these conditions. Talk to your doctor immediately if you experience rapid weight gain, fluid retention, or shortness of breath while taking ACTOS. If you have moderate to severe heart failure, ACTOS is not recommended. Your doctor should perform a blood test to check for liver problems before you start ACTOS and periodically thereafter.
Do not take ACTOS if you have active liver disease. Talk to your doctor immediately if you experience nausea, vomiting, stomach pain, tiredness, loss of appetite, dark urine, or yellowing of the skin. If you are of childbearing age, talk to your doctor before taking ACTOS as it could increase your chance of becoming pregnant. Some people taking ACTOS may experience flu-like symptoms, mild to moderate swelling of legs and ankles, and anemia. When taking ACTOS with insulin or sulfonylureas, you may be at risk for low blood glucose.
While ACTOS may confer some lipid benefits, ACTOS is not indicated to treat lipid disorders and should not be used as a substitute for lipid-lowering therapy.
Eli Lilly and Company
Lilly, a leading innovation-driven corporation, is developing a growing portfolio of first-in-class and best-in-class pharmaceutical products by applying the latest research from its own worldwide laboratories and from collaborations with eminent scientific organizations. Headquartered in Indianapolis, Ind., Lilly provides answers–through medicines and information–for some of the world’s most urgent medical needs. Additional information about Lilly is available on http://www.cesaonline.com
Takeda Pharmaceuticals North America, Inc.
Based in Lincolnshire, Ill., Takeda Pharmaceuticals North America, Inc. is a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, the largest pharmaceutical company in Japan. In the United States, Takeda currently markets oral diabetes and cholesterol-lowering treatments, and through the Takeda Global Research & Development Center, Inc. the company has a robust pipeline with compounds in development for diabetes, sleep, cardiovascular disease and other conditions. Takeda is committed to striving toward better health for individuals and progress in medicine by developing superior pharmaceutical products. To learn more about the company and its products, visit http://www.cesaonline.com .
ACTOS is a registered trademark of Takeda Pharmaceutical Company Limited and used under license by Takeda Pharmaceuticals North America, Inc. and Eli Lilly and Company. Please visit the ACTOS Web site at www.CesaOnline.com for complete Prescribing Information. The brand names included in this piece are properties of their respective owners.
