Pioglitazone Decreases Carotid Intima-Media Thickness in Patients With Type 2 Diabetes Mellitus - Pioglitazone Decreases Carotid Intima-Media Thickness in Patients With Type 2 Diabetes
The goal of the trial was to evaluate the effect of treatment with pioglitazone compared with glimepiride therapy on carotid intima-media thickness (IMT) among patients with type 2 diabetes.
Patients Enrolled: 173
Mean Follow Up: 24 weeks
Mean Patient Age: Mean age 62.6 years
Known type 2 diabetes treated with oral antidiabetic agents, age 40-75 years, HbA1c 6.6%-9.9%, no significant hepatic or renal disease, absence of congestive heart failure (NYHA class II to IV), no cigarette smoking during the previous 6 months, and no known carotid artery stenosis.
Patients were randomized to pioglitazone-based therapy (45 mg/d; n=89) or glimepiride-based therapy (average dose 2.7 mg; n=84). Carotid IMT was evaluated at baseline, 12 weeks and 24 weeks.
At baseline, mean HBA1c was 7.5% and body mass index was 31.8 kg. Duration of diabetes was just over 7 years. Antidiabetic monotherapy was used in 64% of patients. Symptomatic hypoglycemia occurred in 17 patients in each group. Increased body weight occurred more frequently in the pioglitazone group (n=20 vs 2, p<0.0001), as did peripheral edema (n=21 vs 2, p<0.0001).
Compared with baseline, carotid IMT decreased significantly at 12 weeks in the pioglitazone group (-0.033 mm, p<0.0001) but did not differ in the glimepiride group (-0.002 mm, p=NS). At 24 weeks, carotid IMT continued to decrease in the pioglitazone group to a greater degree than the glimepiride group (-0.054 mm vs -0.011 mm, p<0.0001). There was no difference in change in HbA1c between groups at 12 weeks (-0.44% vs -0.51%, p=0.34) or 24 weeks (-0.8% vs -0.6%, p=0.13). CRP at 24 weeks decreased from baseline in the pioglitazone group (-0.80 mg/L) but not in the glimepiride group (-0.13 mg/L, p<0.0005). Glucose was lower in both groups but to a greater degree in the pioglitazone group (-18 mg/dL vs -5 mg/dL, p<0.01). Fasting insulin decreased in the pioglitazone group (-4.69 mU/L, p<0.0001) but not in the glimepiride group (0.37 mU/L).
Among patients with type 2 diabetes, treatment with pioglitazone was associated with a greater reduction in carotid IMT at 24 weeks compared with glimepiride.
Pioglitazone, a part of the thiazolidinedione class of drugs, is an agonists of the peroxisome proliferator-activated receptor (PPAR gamma), which improves insulin sensitivity. Indeed, fasting insulin was reduced in the glimepiride group but not in the glimepiride group. In the much larger PROactive trial, pioglitazone was not associated with a reduction in the primary composite clinical event, which combined both coronary and peripheral events, compared with placebo. However, it was associated with a reduction in the secondary composite endpoint of coronary events (death, MI or stroke). In the present study, pioglitazone was associated with higher rates of edema and weight gain. In PROactive, pioglitazone was associated with increased heart failure and heart failure hospitalizations.
Langenfeld MR, et al. Pioglitazone Decreases Carotid Intima-Media Thickness Independently of Glycemic Control in Patients With Type 2 Diabetes Mellitus. Circulation. 2005;111:2525-2531.
Keywords: Stroke, Carotid Intima-Media Thickness, Diabetes Mellitus, Type 2, Immunosuppressive Agents, Edema, Insulin Resistance, Weight Gain, Peroxisome Proliferator-Activated Receptors, Smoking, Glucose, Sulfonylurea Compounds, Body Mass Index, PPAR gamma, Heart Failure, Hypoglycemic Agents, Carotid Stenosis, Thiazolidinediones, Fasting
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