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

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<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

Pharmacokinetic Model of Circulating Covalent Aggregates of Insulin

Covalent aggregates of insulin in blood of insulin-treated diabetic patients account for as much as 70% (mean 28 ± 3.6%) of serum insulin immunoreactivity. These aggregates may originate in therapeutic insulin, because similar substances account for 0.1–3% of these preparations. Larger amounts in blood imply that aggregates accumulate as a result of delayed clearance. To test and quantify this speculation, we calculated the plasma kinetics of this material in four normal volunteers who received large intravenous doses (30 mU · kg−1 · min−1) of beef-pork crystalline zinc insulin for 120 min. Insulin aggregate and monomer concentrations were measured in blood samples obtained at regular intervals throughout the infusion and during 4 h after discontinuation of insulin. Pharmacokinetic parameters were calculated from the data. Insulin aggregate and monomer serum t½ were 63.6 ± 6.9 and 34.3 ± 2.8 min, respectively, and clearances were 101 ± 10 and 232 ± 47 ml/min. Volume of distribution (Vβ) and volume at steady state (Vss) were 9.1 ± 1.8 and 8.2 ± 2.2 L for insulin aggregate and 11.6 ± 2.8 and 12.2 ± 3.6 L for insulin monomer, respectively. Mean residency time was 141 ± 14 and 114 ± 10 min for insulin aggregate and monomer, respectively [P &amp;lt; .01 for all parameters except Vβ (.014) and Vss (.012), aggregate vs. monomer]. Thus, in relation to insulin monomer, calculated pharmacokinetic parameters of the aggregate predict accumulation after insulin injection. Plasma t½ of the aggregate was almost double that of monomeric insulin; total-body clearance and the corresponding volumes of distribution were smaller.</jats:p