Empagliflozin as add-on to metformin in people with Type 2 diabetes.

AIMS: To investigate the long-term efficacy and safety of empagliflozin as add-on to metformin in people with Type 2 diabetes. METHODS: Of 637 participants treated with empagliflozin 10 mg, empagliflozin 25 mg, or placebo once daily for 24 weeks, 463 (72.7%) were treated in a double-blind extension trial for ≥ 52 weeks. Prespecified exploratory endpoints included changes from baseline in HbA1c , weight and blood pressure at week 76. RESULTS: Compared with placebo, adjusted mean changes from baseline in HbA1c (overall baseline mean ± sd 63 ± 9 mmol/mol [7.9 ± 0.9%]) were -7 mmol/mol [(-0.6%) 95% CI -8, -5 mmol/mol (-0.8, -0.5%); P < 0.001] and -8 mmol/mol [(-0.7%) 95% CI -10, -6 mmol/mol (-0.9, -0.6%); P < 0.001], for empagliflozin 10 mg and 25 mg, respectively. Compared with placebo, adjusted mean changes from baseline in weight were -1.9 kg (95% CI -2.5, -1.3; P < 0.001) and -2.2 kg (95% CI -2.8, -1.6; P < 0.001) for empagliflozin 10 mg and 25 mg, respectively. Empagliflozin led to sustained reductions in systolic blood pressure vs. placebo. Adverse events were reported in 77.7, 80.2 and 72.0% of participants on placebo, empagliflozin 10 mg and empagliflozin 25 mg, respectively. Confirmed hypoglycaemic adverse events (glucose ≤ 3.9 mmol/l and/or event requiring assistance) were reported in 3.4, 4.1 and 4.2% of participants in these groups, respectively. CONCLUSIONS: In people with Type 2 diabetes, empagliflozin 10 mg and 25 mg given as add-on to metformin for 76 weeks were well tolerated and led to sustained reductions in HbA1c , weight and systolic blood pressure.

Use of performance- and image-enhancing substances among recreational athletes: a quantitative analysis of inquiries submitted to the Danish anti-doping authorities.

The use of performance- and image-enhancing drugs/substances (PIED) outside elite sports appears to be increasing, although the current knowledge of the nature of PIED use among recreational athletes is scarce. The present study analyzed enquiries that were submitted to the Danish Anti Doping Agency (ADD) over an 18-month period, to gain knowledge of PIED use among individuals who exercise recreationally in Denmark. One thousand three hundred ninety eight queries were examined with respect to the age and gender of the enquirer, affiliation to sport or exercise and substance in question. The key findings were that the ADD information service is generally used by males in their mid-20s who exercise in gyms and are not engaged in competitive sports. Approximately 15% of the enquirers were users of anabolic androgenic steroids (AAS) or other substances banned within elite sports by the World Anti Doping Agency, and an additional 15% considered using such substances. The present results suggest that there is a pronounced interest in the use of AAS and other PIEDs among Danish gym members.

Oral dabigatran etexilate vs. subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement: the RE-MODEL randomized trial.

BACKGROUND: Oral anticoagulants, such as dabigatran etexilate, an oral, direct thrombin inhibitor, that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism (VTE) after total knee replacement surgery. METHODS: In this randomized, double-blind study, 2076 patients undergoing total knee replacement received dabigatran etexilate, 150 mg or 220 mg once-daily, starting with a half-dose 1-4 hours after surgery, or subcutaneous enoxaparin 40 mg once-daily, starting the evening before surgery, for 6-10 days. Patients were followed-up for 3 months. The primary efficacy outcome was a composite of total VTE (venographic or symptomatic) and mortality during treatment, and the primary safety outcome was the incidence of bleeding events. RESULTS: The primary efficacy outcome occurred in 37.7% (193 of 512) of the enoxaparin group versus 36.4% (183 of 503) of the dabigatran etexilate 220 mg group (absolute difference, -1.3%; 95% CI, -7.3 to 4.6) and 40.5% (213 of 526) of the 150 mg group (2.8%; 95% CI, -3.1 to 8.7). Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion. The incidence of major bleeding did not differ significantly between the three groups (1.3% versus 1.5% and 1.3% respectively). No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up. CONCLUSIONS: Dabigatran etexilate (220 mg or 150 mg) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery.

Quantitative determination of thapsigargins in roots and fruits from Thapsia gymnesica.

Three sesquiterpene lactones, thapsigargin, thapsigargicin, and nortrilobolid, and 6-methoxy-7-geranyloxycoumarin have been isolated from the roots of Thapsia gymnesica (Apiaceae) for the first time. The concentrations of the three thapsigargins in the roots and the fruits have been determined by HPLC analysis.