Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: a real-life worldwide observational study (EDGE).

AIM: Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale 'pragmatic' trials. METHODS: EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA(1c) > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA(1c) < 7% without hypoglycaemia or ≥ 3% increase in body weight. RESULTS: In this large group of T2DM patients, a second OAD was added at mean HbA(1c) of 8.2 ± 1.3%, with no baseline HbA(1c) difference between cohorts. Second-line OAD therapy attained the PEP in the majority of patients, with higher attainment in those prescribed a vildagliptin-based regimen. The adjusted odds ratio was 1.49 (95% CI: 1.42, 1.55; p < 0.001). In patients with baseline HbA(1c) ≥ 7%, SEP 3 was achieved by 35% of patients on a vildagliptin-based combination and by 23% of those receiving comparator combinations. The adjusted odds ratio was 1.96 (95% CI: 1.85, 2.07; p < 0.001). Safety events were reported infrequently and safety profiles of vildagliptin and other OADs were consistent with previous data. CONCLUSION: EDGE demonstrates that in a 'real-life' setting, vildagliptin as second OAD can lower HbA(1c) to target without well-recognised OAD side effects, more frequently than comparator OADs. In addition, EDGE illustrates that conducting large-scale, prospective, real-life studies poses challenges but yields valuable clinical information complementary to RCTs.

Heart rate variability modifications following exercise training in type 2 diabetic patients with definite cardiac autonomic neuropathy.

OBJECTIVES: Cardiac autonomic neuropathy (CAN) as a result of diabetic autonomic neuropathy is positively related to a poor prognosis in diabetic patients. The measurement of heart rate variability (HRV) is a remarkable index of cardiac autonomic dysfunction. The aim of this study was to examine the effects of long-term exercise training on HRV in type 2 diabetic patients with definite CAN. METHODS: Seventeen type 2 diabetic patients with definite CAN (group A: 56.2 years (SD 5.8)) and 15 without CAN (group B: 55.8 years (SD 5.6)) participated in the study. All patients followed an aerobic exercise training programme three times a week for 6 months; the intensity of the session was 70% to 85% of heart rate reserve. At the beginning and end of the study all subjects underwent graded maximal exercise testing with spiroergometry for the evaluation of their aerobic capacity (VO(2)peak). Moreover, time and frequency domain indices of HRV were obtained from 24 h ambulatory continuous ECG Holter recordings. RESULTS: At baseline, all measurements of HRV indices were significantly reduced in group A compared with group B (p<0.05). Moreover, group A reached a significantly lower VO(2)peak by 14.8% compared with group B (p<0.05). Following the exercise training programme, the SD of all normal-to-normal RR intervals in the entire recording (SDNN) was increased by 18.8% (p<0.05) and 13.8% (p<0.05), the square root of the average of sum of squares of difference between adjacent filtered RR intervals (rMSSd) was increased by 35% (p<0.05) and 15.2% (p<0.05), and the percentage of differences between adjacent filtered RR intervals which was greater than 50 ms for the entire analysis (pNN50) was increased by 400% (p<0.05) and 67.9% (p<0.05) in groups A and B, respectively. Regarding the frequency domain indices, only the high frequency power (HF) was found to be significantly increased in group A. At the end of the exercise training programme, SDNN, rMSSd and low frequency power (LF) were significantly lower (24.3% (p<0.05), 20.3% (p<0.05) and 40% (p<0.05), respectively) in group A compared with group B. Also, VO(2)peak increased by 17.8% (p<0.05) in group A and by 11% (p<0.05) in group B. Furthermore, the exercise training programme had significant effects on blood lipid and glucose levels and glycosylated haemoglobin (HbA(1c)) in both groups. CONCLUSIONS: The results indicate that 6-month aerobic exercise training improves the cardiac autonomic nervous system function in type 2 diabetic patients. However, more favourable effects are found in type 2 diabetic patients with definite CAN.