Long-Term Efficacy and Safety of Empagliflozin Monotherapy in Drug-Naïve Patients with Type 2 Diabetes in Indian Subgroup: Results from a 76-week Extension Trial of Phase III, Double-Blind, Randomized Study.

BACKGROUND AND OBJECTIVES: Empagliflozin, a sodium glucose cotransporter-2 inhibitor, was recently evaluated in a randomized, controlled trial (RCT) in drug-naïve Type 2 diabetes mellitus (T2DM) patients managed on diet and exercise therapy. Efficacy and safety of empagliflozin in Indian subgroup of patients from a 76-week extension study of the initial multicentric RCT are reported in this article. MATERIALS AND METHODS: In this study, patients were randomized to empagliflozin 10 mg (E10, n = 24), empagliflozin 25 mg (E25, n = 29), placebo (n = 28) and sitagliptin 100 mg (S100, n = 27). Exploratory efficacy endpoints were changed from baseline to week 76 in glycosylated hemoglobin (HbA1c, %) and fasting blood glucose (mg/dL) along with body weight (kg) and blood pressure (BP) (mmHg) reduction. Safety analysis included clinically relevant adverse events (AEs). RESULTS: In 108 randomized patients, adjusted mean reduction in HbA1c compared to placebo was significant with E10 (-0.81, 95% confidence interval (CI) -1.33, -0.28; P = 0.0029) and E25 (-1.11, 95% CI - 1.60, -0.61; P < 0.0001). HbA1c below 7% at week 76 was achieved in significantly higher number of patients with E10 (20.8%, P < 0.0001) and E25 (28.0%, P < 0.0001). There was significant reduction in adjusted mean weight as compared to placebo with E10 (-1.41, 95% CI - 2.51, -0.31; P = 0.0125) and E25 (-1.50, 95% CI - 2.54, -0.46; P = 0.0051) but nonsignificant with S100 (-0.75 95% CI - 1.86, -0.36; P = 0.1842). BP reduction was numerically higher with empagliflozin compared to placebo. AEs were similar in all treatment groups except for genital infections which were more common in E10 (20.8%) but not in E25 (3.4%) as compared to placebo (3.6%). All treatments were well tolerated with no severe AEs. CONCLUSION: Treatment with empagliflozin was well tolerated and resulted in sustained glycemic efficacy over long-term (76 weeks) in drug-naïve Indian T2DM patients.

Treatment Costs of Stroke Related to Nonvalvular Atrial Fibrillation Patients in India-A Multicenter Observational Study.

OBJECTIVE: The objective of this study was to quantify the direct medical and nonmedical costs of stroke among patients with nonvalvular atrial fibrillation in India. METHODS: An observational, multicenter cost-of-illness study was conducted within large tertiary care hospitals across three metropolitan cities in India. Medical chart records of eligible patients who were hospitalized during the study period were reviewed. A standardized data collection form was designed and used to capture resources expended in the treatment and management of stroke during the inpatient stay. In addition, direct medical and nonmedical outpatient care resources and informal care burden were captured using a detailed questionnaire, following the patients' discharge. Factors associated with acute care costs were investigated using multivariate linear regression analysis. RESULTS: Data were collected on a total of 400 patients with incident strokes. Their mean age was 61.4 ± 9.4 years. About 84% of the patients were diagnosed with ischemic stroke. On average, patients spent 16 ± 10 days in the hospital. Total mean direct health care costs per patient amounted to `504,973 (US $8,020) during the first year, with about 47% (mean `235,471; US $3,750) of the total costs due to the index hospitalization. The modified Rankin scale score was strongly associated with costs, whereby severely disabled patients had 32% higher costs (P = 0.001) compared with moderately disabled patients during the first 3 months postdischarge. CONCLUSIONS: Overall, the financial burden associated with medical care for patients with stroke with atrial fibrillation along with rehabilitation and long-term care costs places a significant demand on health services in India.

Lung epithelial permeability and inhaled furosemide: added dimensions in asthmatics.

OBJECTIVE: Lung clearance rates of inhaled (99m)Tc-DTPA aerosols constitute a sensitive index to evaluate the permeability changes characteristic of airway epithelial damage. It was thought that edema of the airway wall which is reported in asthma could be relieved with a diuretic like furosemide, helping to relieve the symptoms. We intended to study the effect of inhaled furosemide on lung epithelial permeability in asthmatics and smokers with the help of (99m)Tc-DTPA lung clearance test (LCT). METHODS: The study included three groups (n = 15), viz. normal healthy controls, asymptomatic chronic smokers, and chronic persistent asthmatics. Each subject underwent the LCT twice, baseline and post-furosemide (Lasix) study, within a week's interval. The post-furosemide study was carried out 15 min after inhalation of 10 mg of lasix. Lung epithelial permeability was determined in terms of clearance half-life (T (1/2)). RESULTS: The baseline mean T (1/2) values for controls, smokers, and asthmatics were 50.95 +/- 16.58, 20.81 +/- 5.47, 24.06 +/- 6.19 min, respectively. Post-lasix T (1/2) values were 50.83 +/- 15.84, 20.70 +/- 5.65, 41.27 +/- 15.07 min, respectively. There was a significant difference (P < 0.001) in baseline and post-lasix clearance values in asthmatics only. CONCLUSION: Baseline lung epithelial permeability was altered in smokers and asthmatics compared to the controls. Furosemide was effective only in asthmatics in reverting the permeability almost back to the normal range. Inhaled furosemide was effective even in moderate and severe asthmatics. Furosemide has multiple mechanisms of action. It possibly acts at bronchial level in view of the pathology in asthmatics lying in the airways.

Evaluation of immunogenicity and tolerability of a live attenuated hepatitis a vaccine in Indian children.

An open non comparative study of a live attenuated H2 strain Hepatitis A vaccine of Chinese origin was carried out in 143 healthy Indian children aged 1 to 12 years (mean age 4.87 2.76 years; 88 boys, 55 girls). At baseline, all were negative for IgG HAV antibodies and had normal hematological and biochemical indices. Two months after a single dose of the vaccine (given subcutaneously), 137 children (i.e. 95.8 %) developed protective antibodies of IgG > 20 mIU / mL. The hematological and biochemical parameters remained within normal limits. There were no adverse events in any except mild fever in one child. In conclusion, live attenuated H2 strain Hepatitis A vaccine in a single dose was found to be immunogenic and safe in Indian children.