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 Interpretation In this trial, we provide results for 3 years of treatment, with the limitation that withdrawn individuals were not followed up after discontinuation.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
Features that suggest autoimmune pancreatitis include focal or diffuse pancreatic enlargement, with minimal peripancreatic inflammation and absence of vascular encasement or calcification at CT and endoscopic US, and diffuse irregular narrowing of main pancreatic duct, with associated multiple biliary strictures at ERCP.
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...
ERCP plays an important role in the management of postpancreatic surgery problems including biliary and anastomotic strictures, and should be the modality of choice. However, surgical technique may make the afferent limb inaccessible, and the ductal anastomosis difficult to identify in patients with some types of pancreaticoduodenectomy. Closer collaboration between surgeon and endoscopist may allow alterations in surgical technique to improve postoperative ERCP success.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.