Exenatide or glimepiride added to metformin on metabolic control and on insulin resistance in type 2 diabetic patients.

The aim of this study was to evaluate the effect of exenatide compared to glimepiride on body weight, glycemic control and insulin resistance in type 2 diabetic patients taking metformin. One hundred and eleven patients with uncontrolled type 2 diabetes mellitus and intolerant to metformin at the highest dosages (2500-3000 mg/day) were enrolled in this study. Patients were randomized to receive exenatide 5 µg twice a day or glimepiride 1mg three times a day and titrated after 1 month to exenatide 10 µg twice a day or glimepiride 2mg three times a day for 12 months in a randomized, single-blind, controlled study. We evaluated at the baseline and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), HbA(1c), glycemic control, fasting plasma insulin, homeostasis model assessment insulin resistance index (HOMA-IR) index, adiponectin, tumor necrosis factor-α, and high sensitivity-C reactive protein. Both treatments gave a similar improvement of glycemic control, without any differences between the two groups. Only exenatide gave a decrease of BMI, insulin resistance parameters such as fasting plasma insulin, HOMA-IR, and adiponectin and a decrease of inflammatory parameters such as tumor necrosis factor-α, and high sensitivity-C reactive protein. Furthermore, the values obtained with exenatide were significantly better than the values recorded with glimepiride. We can conclude that exenatide was better than glimepiride in improving insulin resistance and inflammatory state. Furthermore, adiponectin increase, and tumor necrosis factor-α reduction seem to be related to weight loss obtained with exenatide.

Cardiac events in 735 type 2 diabetic patients who underwent screening for unknown asymptomatic coronary heart disease: 5-year follow-up report from the Milan Study on Atherosclerosis and Diabetes (MiSAD).

OBJECTIVE: To report the cardiac events in type 2 diabetic outpatients screened for unknown asymptomatic coronary heart disease (CHD) and followed for 5 years. RESEARCH DESIGN AND METHODS: During 1993, 925 subjects aged 40-65 years underwent an exercise treadmill test (ETT). If it was abnormal, the subjects then underwent an exercise scintigraphy. Of the 925 subjects, 735 were followed for 5 years and cardiac events were recorded. RESULTS: At the entry of the study, 638 of the 735 followed subjects had normal ETT, 45 had abnormal ETT with normal scintigraphy, and 52 had abnormal ETT and abnormal scintigraphy. The 52 subjects with abnormal scintigraphy and ETT underwent a cardiological and diabetological follow-up; the subjects with just abnormal ETT had a diabetological follow-up only. During the follow-ups, 42 cardiac events occurred: 1 fatal myocardial infarction (MI), 20 nonfatal MIs, and 10 cases of angina in the 638 subjects with normal ETT; 1 fatal MI in the 45 subjects with normal scintigraphy; and 1 fatal MI and 9 cases of angina in the 52 subjects with abnormal scintigraphy. In these 52 subjects all cardiac events were significantly more frequent (chi(2) = 21.40, P < 0.0001) but the ratio of major (cardiac death and MI) to minor (angina) cardiac events was significantly lower (P = 0.002). Scintigraphy abnormality (hazard ratio 5.47; P < 0.001; 95% CI 2.43-12.29), diabetes duration (1.06; P = 0.021; 1.008-1.106), and diabetic retinopathy (2.371; P = 0.036; 1.059-5.307) were independent predictors of cardiac events on multivariate analysis. CONCLUSIONS: The low ratio of major to minor cardiac events in the positive scintigraphy group may suggest, although it does not prove, that the screening program followed by appropriate management was effective for the reduction of risk of major cardiac events.