Dapagliflozin added to glimepiride in patients with T2DM uncontrolled on sulphonylurea monotherapy significantly improved HbA1c, reduced weight and was generally well tolerated, although events suggestive of genital infections were reported more often in patients receiving dapagliflozin.
Pregabalin binds with high affinity to the alpha2-delta subunit protein of voltage-gated calcium channels and, thereby, reduces release of excitatory neurotransmitters. This 12-week randomised, double-blind, multicentre, placebo-controlled, parallel-group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia (PHN) or painful diabetic peripheral neuropathy (DPN). Patients were randomised to placebo (n=65) or to one of two pregabalin regimens: a flexible schedule of 150, 300, 450, and 600 mg/day with weekly dose escalation based on patients' individual responses and tolerability (n=141) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks (n=132). Both flexible- and fixed-dose pregabalin significantly reduced endpoint mean pain score (primary outcome) versus placebo (P=0.002, P<0.001) and were significantly superior to placebo in improving pain-related sleep interference (P<0.001). The most common adverse events (AEs) for pregabalin-treated patients were dizziness, peripheral oedema, weight gain (not affecting diabetes control), and somnolence. These results are consistent with previous studies' demonstrating pregabalin's efficacy, tolerability, and safety for treatment of chronic neuropathic pain associated with DPN or PHN. Pregabalin dosing aimed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation.
Type 2 Diabetes Mellitus (HEART2D) is a multinational, randomized, controlled trial designed to compare the effects of prandial versus fasting glycemic control on risk for cardiovascular outcomes in patients with type 2 diabetes after acute myocardial infarction (AMI).RESEARCH DESIGN AND METHODS -Patients (type 2 diabetes, aged 30 -75 years) were randomly assigned within 21 days after AMI to the 1) prandial strategy (PRANDIAL) (three premeal doses of insulin lispro targeting 2-h postprandial blood glucose Ͻ7.5 mmol/l) or the 2) basal strategy (BASAL) (NPH twice daily or insulin glargine once daily targeting fasting/premeal blood glucose Ͻ6.7 mmol/l).RESULTS -A total of 1,115 patients were randomly assigned (PRANDIAL n ϭ 557; BASAL n ϭ 558), and the mean patient participation after randomization was 963 days (range 1-1,687 days). The trial was stopped for lack of efficacy. Risks of first combined adjudicated primary cardiovascular events in the PRANDIAL (n ϭ 174, 31.2%) and BASAL (n ϭ 181, 32.4%) groups were similar (hazard ratio 0.98 [95% CI 0.8 -1.21]). Mean A1C did not differ between the PRANDIAL and BASAL groups (7.7 Ϯ 0.1 vs. 7.8 Ϯ 0.1%; P ϭ 0.4) during the study. The PRANDIAL group showed a lower daily mean postprandial blood glucose (7.8 vs. 8.6 mmol/l; P Ͻ 0.01) and 2-h postprandial blood glucose excursion (0.1 vs. 1.3 mmol/l; P Ͻ 0.001) versus the BASAL group. The BASAL group showed lower mean fasting blood glucose (7.0 vs. 8.1 mmol/l; P Ͻ 0.001) and similar daily fasting/premeal blood glucose (7.7 vs. 7.3 mmol/l; P ϭ 0.233) versus the PRANDIAL group.CONCLUSIONS -Treating diabetic survivors of AMI with prandial versus basal strategies achieved differences in fasting blood glucose, less-than-expected differences in postprandial blood glucose, similar levels of A1C, and no difference in risk for future cardiovascular event rates.
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