3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

Background Liraglutide 3\ub70 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\ub70 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\ub77 times longer with liraglutide than with placebo (95% CI 1\ub79 to 3\ub79, p<0\ub70001), corresponding with a hazard ratio of 0\ub721 (95% CI 0\ub713\u20130\ub734). Liraglutide induced greater weight loss than placebo at week 160 (\u20136\ub71 [SD 7\ub73] vs 121\ub79% [6\ub73]; estimated treatment difference 124\ub73%, 95% CI 124\ub79 to 123\ub77, p<0\ub70001). 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\ub70 mg might provide health benefits in terms of reduced risk of diabetes in individuals with obesity and prediabetes. Funding Novo Nordisk, Denmark

Plasma appearance and disappearance of an oral dose of 25-hydroxyvitamin D2 in healthy adults

25-Hydroxyvitamin D (25(OH)D) half-life is a potential biomarker for investigating vitamin D metabolism and requirements. We performed a pilot study to assess the approach and practical feasibility of measuring 25(OH)D half-life after an oral dose. A total of twelve healthy Gambian men aged 18–23 years were divided into two groups to investigate the rate and timing of (1) absorption and (2) plasma disappearance after an 80 nmol oral dose of 25(OH)D2. Fasting blood samples were collected at baseline and, in the first group, every 2 h post-dose for 12 h, at 24 h, 48 h and on day 15. In the second group, fasting blood samples were collected on days 3, 4, 5, 6, 9, 12, 15, 18 and 21. Urine was collected for 2 h after the first morning void at baseline and on day 15. 25(OH)D2 plasma concentration was measured by ultra-performance liquid chromatography-tandem MS/MS and corrected for baseline. Biomarkers of vitamin D, Ca and P metabolism were measured at baseline and on day 15. The peak plasma concentration of 25(OH)D2 was 9·6 (sd 0·9) nmol/l at 4·4 (sd 1·8) h. The terminal slope of 25(OH)D2 disappearance was identified to commence from day 6. The terminal half-life of plasma 25(OH)D2 was 13·4 (sd 2·7) d. There were no significant differences in plasma 25(OH)D3, total 1,25(OH)2D, parathyroid hormone, P, Ca and ionised Ca and urinary Ca and P between baseline and day 15 and between the two groups. The present study provides data on the plasma response to oral 25(OH)D2 that will underpin and contribute to the further development of studies to investigate 25(OH)D half-life

Ureteroscopic Lithotripsy Using Swiss Lithoclast for Treatment of Ureteral Calculi: 12-Years Experience

Ureteroscopic lithotripsy using Swiss Lithoclast was performed in 411 cases from January 1996 to September 2007 in a single hospital. Medical records of 341 cases, in which Swiss Lithoclast was successfully applied, were available for this retrospective study. We used 9.5Fr and 10Fr Storz rigid ureteroscopes. A success was defined as being free of stone-related symptoms and residual stones larger than 2 mm. Sixty one stones were located in the upper ureter, 49 stones were in the mid ureter, and 231 stones were in the lower ureter. The overall success rate was 93.5%. The success rate of upper ureter stone (80.3%) was significantly lower compared with those of mid (93.8%) and lower (96.9%) ureter stones (P=0.001). The higher the calculi was located within the ureter, the more chance of upward migration there was (P<0.001). The success rate in male patients was lower than in female patients without a statistical significance (P=0.068). The success rate decreased as the size of the stone increased (P<0.001), and as the degree of hydronephrosis increased (P=0.03). Perforation rates were 4.9%, 4.1%, and 2.6% from upper to lower ureter stone group. Ureteroscopic lithotripsy using Swiss Lithoclast is a safe and useful treatment modality for ureteral calculi

Management of obesity in adults: European clinical practice guidelines

Stworzenie jednolitych wytycznych postępowania w otyłości jest złożone. Obejmują one zarówno zalecenia diagnostyczne, lecznicze, jak i działania w zakresie prewencji. Wobec wielu publikacji i różnic poglądów oraz świadomości krótkotrwałości efektu odchudzającego u poszczególnych osób wielu uważa, że trudno jest ustalić właściwe postępowanie w otyłości. Różnorodność zasad postępowania w kraju oraz pomiędzy regionami Europy utrudnia ustalenie i wprowadzenie standardów. W ustalaniu obecnych wytycznych za podstawę brano wiedzę opartą na dowodach (EBM), a w razie wątpliwości uzupełniano na podstawie doświadczenia klinicznego i różnorodności regionalnej oraz uzgodnionego stanowiska zespołu. W podsumowaniu stwierdzono, że: 1) lekarz jest odpowiedzialny za rozpoznanie otyłości jako choroby oraz pomoc w odpowiedniej prewencji i leczeniu; 2) leczenie powinno być oparte na dobrej praktyce klinicznej i EBM; 3) leczenie otyłości powinno wyznaczać indywidualne realne cele i dożywotnie postępowanie.The development of consensus guidelines for obesity is complex. It involves recommending both treatment interventions and interventions related to screening and prevention. With so many publications and claims, and with the awareness that success for the individual is short-lived, many find it difficult to know what action is appropriate in the management of obesity. Furthermore, the significant variation in existing service provision both within countries as well as across the regions of Europe makes a standardised approach, even if evidence-based, difficult to implement. In formulating these guidelines, we have attempted to use an evidence based approach while allowing flexibility for the practicing clinician in domains where evidence is currently lacking and ensuring that in treatment there is recognition of clinical judgment and of regional diversity as well as the necessity of an agreed approach by the individual and family. We conclude that 1) physicians have a responsibility to recognise obesity as a disease and help obese patients with appropriate prevention and treatment, 2) treatment should be based on good clinical care and evidence- based interventions and 3) obesity treatment should focus on realistic goals and lifelong management

Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: a summary of available findings

Considerable interest has been shown in the ability of caloric restriction (CR) to improve multiple parameters of health and to extend lifespan. CR is the reduction of caloric intake - typically by 20 - 40% of ad libitum consumption - while maintaining adequate nutrient intake. Several alternatives to CR exist. CR combined with exercise (CE) consists of both decreased caloric intake and increased caloric expenditure. Alternate-day fasting (ADF) consists of two interchanging days; one day, subjects may consume food ad libitum (sometimes equaling twice the normal intake); on the other day, food is reduced or withheld altogether. Dietary restriction (DR) - restriction of one or more components of intake (typically macronutrients) with minimal to no reduction in total caloric intake - is another alternative to CR. Many religions incorporate one or more forms of food restriction. The following religious fasting periods are featured in this review: 1) Islamic Ramadan; 2) the three principal fasting periods of Greek Orthodox Christianity (Nativity, Lent, and the Assumption); and 3) the Biblical-based Daniel Fast. This review provides a summary of the current state of knowledge related to CR and DR. A specific section is provided that illustrates related work pertaining to religious forms of food restriction. Where available, studies involving both humans and animals are presented. The review includes suggestions for future research pertaining to the topics of discussion

A randomized, controlled trial of 3.0 mg of liraglutide in weight management

BACKGROUND Obesity is a chronic disease with serious health consequences, but weight loss is difficult to maintain through lifestyle intervention alone. Liraglutide, a glucagonlike peptide-1 analogue, has been shown to have potential benefit for weight management at a once-daily dose of 3.0 mg, injected subcutaneously. METHODS We conducted a 56-week, double-blind trial involving 3731 patients who did not have type 2 diabetes and who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of at least 30 or a BMI of at least 27 if they had treated or untreated dyslipidemia or hypertension. We randomly assigned patients in a 2:1 ratio to receive once-daily subcutaneous injections of liraglutide at a dose of 3.0 mg (2487 patients) or placebo (1244 patients); both groups received counseling on lifestyle modification. The coprimary end points were the change in body weight and the proportions of patients losing at least 5% and more than 10% of their initial body weight. RESULTS At baseline, the mean (±SD) age of the patients was 45.1±12.0 years, the mean weight was 106.2±21.4 kg, and the mean BMI was 38.3±6.4; a total of 78.5% of the patients were women and 61.2% had prediabetes. At week 56, patients in the liraglutide group had lost a mean of 8.4±7.3 kg of body weight, and those in the placebo group had lost a mean of 2.8±6.5 kg (a difference of -5.6 kg; 95% confidence interval, -6.0 to -5.1; P&lt;0.001, with last-observation-carried-forward imputation). A total of 63.2% of the patients in the liraglutide group as compared with 27.1% in the placebo group lost at least 5% of their body weight (P&lt;0.001), and 33.1% and 10.6%, respectively, lost more than 10% of their body weight (P&lt;0.001). The most frequently reported adverse events with liraglutide were mild or moderate nausea and diarrhea. Serious events occurred in 6.2% of the patients in the liraglutide group and in 5.0% of the patients in the placebo group. CONCLUSIONS In this study, 3.0 mg of liraglutide, as an adjunct to diet and exercise, was associated with reduced body weight and improved metabolic control. (Funded by Novo Nordisk; SCALE Obesity and Prediabetes NN8022-1839 ClinicalTrials.gov number, NCT01272219.)

A systematic review, meta-analysis, and meta-regression of the impact of diurnal intermittent fasting during Ramadan on body weight in healthy subjects aged 16 years and above

PURPOSE: Studies on the effect of Ramadan diurnal intermittent fasting (RDIF) on body weight have yielded conflicting results. Therefore, we conducted a systematic review and meta-analysis to estimate the effect size of body weight changes in healthy, non-athletic Muslims practicing Ramadan fasting, and to assess the effect of covariates such as age, sex, fasting time duration, season, and country, using subgroup analysis, and meta-regression. Covariate adjustments were performed to explain the variability of weight change in response to Ramadan fasting.METHODS: CINAHL, Cochrane, EBSCOhost, EMBASE, Google Scholar, ProQuest Medical, PubMed/MEDLINE, ScienceDirect, Scopus, and Web of Science databases were searched from date of inception in 1950 to the end of August 2019.RESULTS: Eighty-five studies, conducted in 25 countries during 1982-2019, were identified. RDIF yielded a significant, but small reduction in body weight (K = 85, number of subjects, N = 4176 (aged 16-80 years), Hedges' g =- 0.360, 95% confidence interval (CI) - 0.405 to - 0.315, I2 = 45.6%), this effect size translates into difference in means of - 1.022 kg (95% CI - 1.164 kg to - 0.880 kg). Regression analysis for moderator covariates revealed that fasting time (min/day) is a significant (P &lt; 0.05) moderator for weight change at the end of Ramadan, while age and sex are not. Variable effects for the season and country were found.CONCLUSION: RDIF may confer a significant small reduction in body weight in non-athletic healthy people aged 16 years and above, directly associated with fasting time and variably correlated with the season, and country.</p

3 years of liraglutide versus placebo for type 2 diabetes risk reduction and weight management in individuals with prediabetes: a randomised, double-blind trial

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&lt;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&lt;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