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

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.)

Effects of Once-Weekly Exenatide on Cardiovascular Outcomes in Type 2 Diabetes.

Abstract BACKGROUND: The cardiovascular effects of adding once-weekly treatment with exenatide to usual care in patients with type 2 diabetes are unknown. METHODS: We randomly assigned patients with type 2 diabetes, with or without previous cardiovascular disease, to receive subcutaneous injections of extended-release exenatide at a dose of 2 mg or matching placebo once weekly. The primary composite outcome was the first occurrence of death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. The coprimary hypotheses were that exenatide, administered once weekly, would be noninferior to placebo with respect to safety and superior to placebo with respect to efficacy. RESULTS: In all, 14,752 patients (of whom 10,782 [73.1%] had previous cardiovascular disease) were followed for a median of 3.2 years (interquartile range, 2.2 to 4.4). A primary composite outcome event occurred in 839 of 7356 patients (11.4%; 3.7 events per 100 person-years) in the exenatide group and in 905 of 7396 patients (12.2%; 4.0 events per 100 person-years) in the placebo group (hazard ratio, 0.91; 95% confidence interval [CI], 0.83 to 1.00), with the intention-to-treat analysis indicating that exenatide, administered once weekly, was noninferior to placebo with respect to safety (P<0.001 for noninferiority) but was not superior to placebo with respect to efficacy (P=0.06 for superiority). The rates of death from cardiovascular causes, fatal or nonfatal myocardial infarction, fatal or nonfatal stroke, hospitalization for heart failure, and hospitalization for acute coronary syndrome, and the incidence of acute pancreatitis, pancreatic cancer, medullary thyroid carcinoma, and serious adverse events did not differ significantly between the two groups. CONCLUSIONS: Among patients with type 2 diabetes with or without previous cardiovascular disease, the incidence of major adverse cardiovascular events did not differ significantly between patients who received exenatide and those who received placebo. (Funded by Amylin Pharmaceuticals; EXSCEL ClinicalTrials.gov number, NCT01144338 .)

Dietary behaviours of adolescents from urban and rural areas in the district of Szamotuły - a preliminary study

Introduction: Numerous factors and conditions affect the dietary behaviours of the young population. Urban-rural differences may also influence the lifestyle of adolescents, including diet. Aim: To describe dietary behaviours of two young populations: living in urban or rural areas in the district of Szamotuły (a city with a population of 19,000 inhabitants). Material and methods: 116 adolescents aged 15-17 years were included to this preliminary study and asked to answer questions concerning health and lifestyle. Results: No statistically significant difference was detected in the number of meals eaten daily, and 3 meals a day was the most frequent answer (45.9% in the rural group and 32.7% in the urban group). About 41.0% of rural subjects and 50.9% of urban ones admitted that they ate fresh fruit and vegetables every day. There was no statistically significant difference in the medium consumption frequency of fresh fruit, vegetable, fish, sweets and salty snacks. Conclusions: 1. Between rural and urban adolescents no statistically significant differences were observed in dietary behaviours concerning medium number of meals eaten daily, medium frequency of fresh fruit and vegetable consumption, medium monthly frequency of fish consumption, medium weekly frequency of consumption of sweets and salty snacks. 2. More than a half of the young rural dwellers preferred more salty meals in contrast to over 56% of urban youths who preferred less salty meals. Both urban and rural adolescents most often declared that eat sweets and salty snacks daily. 3. There is a great need to change the dietary habits of teenagers, especially in avoiding an over-intake of high fat and high energy products, in order to reduce the rising prevalence of obesity among adolescents

Analysis of lifestyle of young adults in the rural and urban areas

An unhealthy lifestyle among young people is a serious and often unnoticed problem. It seems that there are differences in the lifestyle of young people from rural and urban areas. The objective of this study was to compare eating habits and physical activity of young adults according to their body weight, gender and place of residence. The study involved a group of 18-year-olds from rural and urban environments. The study included 50% girls and 50% of boys in each group, selected by simple random sampling (SRS). The author-designed questionnaire evaluating the nutrition habits and physical activity was provided. It was found that in the group of boys the value of BMI was markedly higher than in girls. Compared to the normal weight, young overweight adults ate meals more frequency, the majority preferred meat dishes, more often ate under the stress, and had lower physical activity. It was found that gender had a significant impact on the studied parameters. The girls ate meals more frequent during the day, the majority preferred fruit and vegetable, but had lower physical activity than the boys. It was found that the young adults from the rural area preferred fast food and frequently ate sweets. Compared to the subjects from the urban environment, the young adults living in the countryside consumed fewer meals daily and were more physical active. About a half of the studied adults were not satisfied with their weight, and nearly 40% of the subjects in both groups admitted that they had made effective or ineffective attempts to lose weight. The lifestyles of young people in rural and urban areas were slightly different; however, dietary factors which predispose to weight gain were comparable in both groups. In the rural areas, the most frequent nutritional faults were a preference for fast food, frequent consumption of sweets, and few meals during the day. A positive aspect of the lifestyle of young people in the rural areas was a relatively high level of physical activity and the small effect of stress on excessive consumption

An assessment of dietary intake and state of nutritional in hypertensive patients from rural and urban areas of Greater Poland

The aim of this study was to determine the nutritional factors connected with the prevalence of hypertension in rural and urban areas of Greater Poland. The study consisted of 308 people aged 35-62, with essential hypertension but without any other coexisting disorders. The studied group consisted of 154 residents of Poznań (79 women and 75 men) and 152 inhabitants of rural areas in Greater Poland (78 women and 74 men). Participants were randomly assigned to the study. Nutritional state assessment was based on Body Mass Index (BMI) and body fat percentage. Dietary intake were assessed with a 24-hour nutritional survey from 3 consecutive days. Analysis of anthropometric examination results showed a large prevalence of obesity in the studied group. Moreover people living in rural areas had a significantly higher BMI and body fat percentage than those living in a city. It has been proved that the patients with hypertension consume food with an excess of fat and a shortage of fibre, antioxidant vitamins, potassium, calcium and magnesium. The total food rations of rural dwellers consisted of larger amounts of fat, cholesterol and vitamin A compared to those of city dwellers. Present studies have shown incorrect dietary intake among patients with hypertension, often related to the coexistence of overweight and obesity. Obtained results indicate significantly worse eating habits and state of nutrition among rural inhabitants

Effects on office and home blood pressure of the lercanidipine-enalapril combination in patients with Stage 2 hypertension: a European randomized, controlled clinical trial.

OBJECTIVES: The aim of this study was to evaluate the efficacy and safety of combinations of lercanidipine (L) and enalapril (E) at different doses on office and home blood pressure (BP) in patients with Stage 2 hypertension. STUDY DESIGN: This was a randomized, double-blind, placebo-controlled, factorial study conducted in 100 centres from seven countries. Patients with office DBP 100-109\u200ammHg and home DBP at least 85\u200ammHg at the end of a 2-week placebo run-in period were randomized to a 10-week treatment with placebo, L (10 or 20\u200amg), E (10 or 20\u200amg) or the four L-E combinations. The efficacy parameters were office DBP at trough (primary), SBP at trough and home SBP and DBP. Office BP was measured at each visit in both the sitting and the standing position, while home BP was measured twice in the morning and twice in the evening for at least 3 days before treatment and at study end. Safety parameters included adverse events, laboratory tests and 12-lead ECG. RESULTS: A total of 1039 patients were randomized (48% men, mean age 54 years, mean BMI 30\u200akg/m, 40% obese patients). Baseline BP was similar in all groups and lower for home than for office values (149/95 and 159/103\u200ammHg, respectively). A marked placebo effect was observed on office but not on home BP. Combination therapy was superior to placebo at all doses for both office and home BP. The greatest effect was observed in the L20/E20 group, in which the SBP/DBP fall amounted to -19.2/-15.2 and -13.2/-7.5\u200ammHg for sitting office and home BP, respectively. Similar reductions were observed on standing office BP. The L20/E20 combination was associated with less cough, palpitations and leg oedema than monotherapies, with no increased rate of dizziness or hypotension. CONCLUSION: In Stage 2 hypertension, a fixed-dose combination of L and E ensures a control of both office and out-of-office BP, with a favourable tolerability profile

Effects of the lercanidipine-enalapril combination vs. the corresponding monotherapies on home blood pressure in hypertension: evidence from a large database

Objective: To compare a combination of a dihydropyridine calcium-channel blocker with an angiotensin converting enzyme inhibitor vs. monotherapy with one or the other drug and placebo for their effects on home blood pressure (HBP). Methods: After a 2-week placebo wash-out, patients with an elevated office blood pressure (BP) (diastolic 100-109 and systolic =85 mmHg) were randomized double-blind to a 10-week treatment with placebo, lercanidipine, 10 or 20 mg daily, enalapril, 10 or 20 mg daily, or the four possible combinations. In addition to office BP, HBP was self-measured via a validated semiautomatic device twice in the morning and twice in the evening during the 7 days before randomization and at the end of treatment. Baseline and treatment HBP values were separately averaged for each day, morning, evening or the whole monitoring period, excluding the first day. Day-by-day HBP variability was defined as the SD or the variation coefficient of the daily BP averages. Results: Eight hundred and fifty-four patients with valid HBP recordings at baseline and at the end of treatment were analyzed (intention-to-treat population). From the baseline value (147.0+/-11.6 mmHg) systolic/diastolic HBP showed a small reduction (average baseline-adjusted change: -1.8/-1.6 mmHg) with placebo, a more marked significant fall with monotherapies (-8.8/-5.9 mmHg, P < 0.001/<0.001 vs. placebo) and even more with combination treatment (11.6/-7.6 mmHg, P < 0.001/ < 0.001 vs. placebo and P < 0.01/ < 0.05 vs. monotherapy). A similar pattern was observed for each of the days of the BP self-monitoring period as well as for either morning or evening values, although the difference between mono and combination treatment appeared to be consistently significant for the morning values only. Day-by-day systolic BP-SD was unaffected by placebo and slightly reduced by drug treatments, with no, however, significant changes in SBP-variation coefficient. Baseline and end of treatment HBP values showed a limited correlation with office BP values, this being particularly the case for treatment-induced changes (correlation coefficients: 0.37 for systolic and 0.45 for diastolic BP). Conclusion: This large HBP database shows that the lercanidipine-enalapril combination lowers HBP more effectively than the corresponding monotherapies and placebo, and that this greater effect is consistent between days. Trial Registration: ClinicalTrials.gov identifier: NCT01093807