Background Liraglutide 3·0 mg was shown to reduce bodyweight and improve glucose metabolism after the 56-week period of this trial, one of four trials in the SCALE programme. In the 3-year assessment of the SCALE Obesity and Prediabetes trial we aimed to evaluate the proportion of individuals with prediabetes who were diagnosed with type 2 diabetes. Methods In this randomised, double-blind, placebo-controlled trial, adults with prediabetes and a body-mass index of at least 30 kg/m2, or at least 27 kg/m2 with comorbidities, were randomised 2:1, using a telephone or web-based system, to once-daily subcutaneous liraglutide 3·0 mg or matched placebo, as an adjunct to a reduced-calorie diet and increased physical activity. Time to diabetes onset by 160 weeks was the primary outcome, evaluated in all randomised treated individuals with at least one post-baseline assessment. The trial was conducted at 191 clinical research sites in 27 countries and is registered with ClinicalTrials.gov, number NCT01272219. Findings The study ran between June 1, 2011, and March 2, 2015. We randomly assigned 2254 patients to receive liraglutide (n=1505) or placebo (n=749). 1128 (50%) participants completed the study up to week 160, after withdrawal of 714 (47%) participants in the liraglutide group and 412 (55%) participants in the placebo group. By week 160, 26 (2%) of 1472 individuals in the liraglutide group versus 46 (6%) of 738 in the placebo group were diagnosed with diabetes while on treatment. The mean time from randomisation to diagnosis was 99 (SD 47) weeks for the 26 individuals in the liraglutide group versus 87 (47) weeks for the 46 individuals in the placebo group. Taking the different diagnosis frequencies between the treatment groups into account, the time to onset of diabetes over 160 weeks among all randomised individuals was 2·7 times longer with liraglutide than with placebo (95% CI 1·9 to 3·9, p<0·0001), corresponding with a hazard ratio of 0·21 (95% CI 0·13–0·34). Liraglutide induced greater weight loss than placebo at week 160 (–6·1 [SD 7·3] vs −1·9% [6·3]; estimated treatment difference −4·3%, 95% CI −4·9 to −3·7, p<0·0001). Serious adverse events were reported by 227 (15%) of 1501 randomised treated individuals in the liraglutide group versus 96 (13%) of 747 individuals in the placebo group. Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation. Liraglutide 3·0 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark

OBJECTIVE -A randomized, parallel-group, open-label, multicenter 16-week clinical trial compared efficacy and safety of repaglinide monotherapy and nateglinide monotherapy in type 2 diabetic patients previously treated with diet and exercise.RESEARCH DESIGN AND METHODS -Enrolled patients (n ϭ 150) had received treatment with diet and exercise in the previous 3 months with HbA 1c Ͼ7 and Յ12%. Patients were randomized to receive monotherapy with repaglinide (n ϭ 76) (0.5 mg/meal, maximum dose 4 mg/meal) or nateglinide (n ϭ 74) (60 mg/meal, maximum dose 120 mg/meal) for 16 weeks. Primary and secondary efficacy end points were changes in HbA 1c and fasting plasma glucose (FPG) values from baseline, respectively. Postprandial glucose, insulin, and glucagon were assessed after a liquid test meal (baseline, week 16). Safety was assessed by incidence of adverse events or hypoglycemia. RESULTS -Mean baselineHbA 1c values were similar in both groups (8.9%). Final HbA 1c values were lower for repaglinide monotherapy than nateglinide monotherapy (7.3 vs. 7.9%). Mean final reductions of HbA 1c were significantly greater for repaglinide monotherapy than nateglinide monotherapy (Ϫ1.57 vs. Ϫ1.04%; P ϭ 0.002). Mean changes in FPG also demonstrated significantly greater efficacy for repaglinide than nateglinide (Ϫ57 vs. Ϫ18 mg/dl; P Ͻ 0.001). HbA 1c values Ͻ7% were achieved by 54% of repaglinide-treated patients versus 42% for nateglinide. Median final doses were 6.0 mg/day for repaglinide and 360 mg/day for nateglinide. There were 7% of subjects treated with repaglinide (five subjects with one episode each) who had minor hypoglycemic episodes (blood glucose Ͻ50 mg/dl) versus 0 patients for nateglinide. Mean weight gain at the end of the study was 1.8 kg in the repaglinide group as compared with 0.7 kg for the nateglinide group.CONCLUSIONS -In patients previously treated with diet and exercise, repaglinide and nateglinide had similar postprandial glycemic effects, but repaglinide monotherapy was significantly more effective than nateglinide monotherapy in reducing HbA 1c and FPG values after 16 weeks of therapy. Diabetes Care 27:1265-1270, 2004R epaglinide (Prandin) and nateglinide (Starlix) are short-acting insulin secretagogues that are approved for the treatment of type 2 diabetes (1,2). Both of these agents have relatively short elimination half-lives (1 h for repaglinide and 1.5 h for nateglinide). When administered at mealtimes, both agents produce peak insulin stimulation during the postprandial period, when physiological insulin needs are maximal. Clinical trials have demonstrated that both agents increase insulin response to postprandial glucose, resulting in reductions of HbA 1c and fasting plasma glucose (FPG) levels.Although both repaglinide and nateglinide stimulate insulin secretion by inhibition of the ATP-dependent potassium channels of ␤-cells, the molecular binding site of repaglinide is different from that of nateglinide and sulfonylureas (3-5). Clinical trial comparisons of repaglinide versus sulfonylurea mono...

Subgroup analysis of the Irbesartan/Hydrochlorothiazide Blood Pressure Reductions in Diverse Patient Populations (INCLUSIVE) trial evaluated the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients aged 65 years or older with uncontrolled systolic blood pressure (SBP) after >or= 4 weeks of antihypertensive monotherapy. The INCLUSIVE trial was a prospective, open-label, single-arm trial carried out in 119 sites. Of 844 patients completing placebo treatment, 212 were aged 65 years or older. Participants received treatment with placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and then irbesartan/HCTZ 300/25 mg (8 weeks). From baseline to week 18 (n=184, intent-to-treat population), mean change in SBP was -23.0+/-13.3 mm Hg (P<.001) and diastolic BP (DBP) was -10.9+/-7.7 mm Hg (P<.001). Mean SBP/DBP at study end was 134.0+/-14.7/75.1+/-8.4 mm Hg, and SBP, DBP, and SBP/DBP goal was achieved in 73%, 96%, and 72% of patients, respectively. Irbesartan/HCTZ combination therapy allowed SBP goal attainment in 73% of patients aged 65 years or older whose hypertension was previously uncontrolled with antihypertensive monotherapy.

Innovative Medical Platform Optimizing Research and Technology (IMPORT)> Background: A medical group, pharmaceutical company, and data harvesting and integration company collaborated to test an innovative approach to quality improvement (QI) that utilizes clinical expertise, advanced outcomes analytics, electronic medical records (EMR), and a cloud technology data harvesting platform. The objective of this project was to measure the ability of this collaborative project to effectively and efficiently identify quality improvement opportunities. Methods: This was a retrospective EMR analysis which utilized Solution for Quality Improvement (SQI) platform on an advanced electronic medical record system. All patients in one primary care medical practice seen from 7/1/2009 - 7/31/2011 were included. The primary outcomes were effectiveness of the platform to integrate data, measured by data density of diabetes laboratory and clinical quality performance values from structured EMR fields and unstructured physician notes; and efficiency, measured as the time period from SQI data mapping to final results analysis. A secondary outcome was the ability of the project to identify and target meaningful QI opportunities. Results: SQI collected data from 9,294 patient records, including 73,706 office visits and 35,602 physician dictated visit notes. Of these records, 6,251 cardiovascular patients were identified with diabetic patients accounting for 1,561 (25%) of these. Values and measurement dates for A1c, LDL, and blood pressure values were harvested in 83%, 75%, and 96% of these diabetic patients, respectively. The collection of other diabetic preventive services performance indicators was relatively low. Additional QI is being done to ensure complete capture of data. The time period for analysis, including 3 iterative rounds of expanded data identification, was 15 weeks total. Through this project, 3 specific areas of QI were prioritized: improve dictation/documentation of preventative diabetes care recommendations; implement diabetes panel management; and develop electronic diabetes patient reported outcomes screening tools. Conclusion: This collaboration led to an efficient and effective QI analysis in diabetes care. Results of the analysis have led to development and implementation of meaningful QI initiatives. Future implications include the use of this project’s approach to rapidly re-measure performance after implementation of the QI initiatives and expansion of the collaboration from a 4 physician practice to the network of 100 primary care physicians.