The effect of continuing vs withdrawing treatment with semaglutide, a glucagon-like peptide 1 receptor agonist, on weight loss maintenance in people with overweight or obesity is unknown.
To compare ...continued once-weekly treatment with subcutaneous semaglutide, 2.4 mg, with switch to placebo for weight maintenance (both with lifestyle intervention) in adults with overweight or obesity after a 20-week run-in with subcutaneous semaglutide titrated to 2.4 mg weekly.
Randomized, double-blind, 68-week phase 3a withdrawal study conducted at 73 sites in 10 countries from June 2018 to March 2020 in adults with body mass index of at least 30 (or ≥27 with ≥1 weight-related comorbidity) and without diabetes.
A total of 902 participants received once-weekly subcutaneous semaglutide during run-in. After 20 weeks (16 weeks of dose escalation; 4 weeks of maintenance dose), 803 participants (89.0%) who reached the 2.4-mg/wk semaglutide maintenance dose were randomized (2:1) to 48 weeks of continued subcutaneous semaglutide (n = 535) or switched to placebo (n = 268), plus lifestyle intervention in both groups.
The primary end point was percent change in body weight from week 20 to week 68; confirmatory secondary end points were changes in waist circumference, systolic blood pressure, and physical functioning (assessed using the Short Form 36 Version 2 Health Survey, Acute Version SF-36).
Among 803 study participants who completed the 20-week run-in period (with a mean weight loss of 10.6%) and were randomized (mean age, 46 SD, 12 years; 634 79% women; mean body weight, 107.2 kg SD, 22.7 kg), 787 participants (98.0%) completed the trial and 741 (92.3%) completed treatment. With continued semaglutide, mean body weight change from week 20 to week 68 was -7.9% vs +6.9% with the switch to placebo (difference, -14.8 95% CI, -16.0 to -13.5 percentage points; P < .001). Waist circumference (-9.7 cm 95% CI, -10.9 to -8.5 cm), systolic blood pressure (-3.9 mm Hg 95% CI, -5.8 to -2.0 mm Hg), and SF-36 physical functioning score (2.5 95% CI, 1.6-3.3) also improved with continued subcutaneous semaglutide vs placebo (all P < .001). Gastrointestinal events were reported in 49.1% of participants who continued subcutaneous semaglutide vs 26.1% with placebo; similar proportions discontinued treatment because of adverse events with continued semaglutide (2.4%) and placebo (2.2%).
Among adults with overweight or obesity who completed a 20-week run-in period with subcutaneous semaglutide, 2.4 mg once weekly, maintaining treatment with semaglutide compared with switching to placebo resulted in continued weight loss over the following 48 weeks.
ClinicalTrials.gov Identifier: NCT03548987.
Link between obesity and type 2 diabetes Golay, A.; Ybarra, J.
Best Practice & Research Clinical Endocrinology & Metabolism,
12/2005, Volume:
19, Issue:
4
Journal Article
Peer reviewed
The relationship between obesity and diabetes is of such interdependence that the term ‘diabesity’ has been coined. The passage from obesity to diabetes is made by a progressive defect in insulin ...secretion coupled with a progressive rise in insulin resistance.
Both insulin resistance and defective insulin secretion appear very prematurely in obese patients, and both worsen similarly towards diabetes. Thus, the classic ‘hyperbolic relationship’ between insulin resistance and insulin secretion and the ‘glucose allostasis concept’ remain prevailing concepts in this particular field of knowledge.
An increase in overall fatness, preferentially of visceral as well as ectopic fat depots, is specifically associated with insulin resistance. The accumulation of intramyocellular lipids may be due to reduced lipid oxidation capacity. The ability to lose weight is related to the capacity to oxidize fat. Thus, a relative defect in fat oxidation capacity is responsible for energy economy and hampered weight loss.
Poor adherence to medical treatment is one of the main reasons why patients do not achieve the full benefits of their therapy. It also has a substantial financial weight in terms of money wasted for ...unused medication and increased healthcare costs including hospitalization due to clinical complications.
To provide an overview and examples of the financial and economic consequences of poor adherence to treatment, techniques and devices for monitoring adherence and interventions for improvement of treatment adherence.
New electronic devices with monitoring features may help to objectively monitor patients' adherence to a treatment regimen that can help a healthcare professional determine how to intervene to improve adherence and subsequent clinical outcome. Interventions that aim to enhance adherence may confer cost-effectiveness benefits in some indications and settings. The nature of the intervention(s) used depends on a range of factors, including patient preference, therapy area and cost of the intervention. However, there is a pressing need for rigorous trials, as current studies often have major flaws in the economic methodology, especially in terms of incremental analysis and sensitivity analysis.
This review has focused on a limited number of therapeutic areas as coverage of a more extensive range of diseases may be beyond the scope of such a summary. Nevertheless, the examples are representative of the challenges encountered in many other diseases.
The clinical and economic consequences of non-adherence and interventions to improve compliance reflect the nature and severity of non-adherence, as well as the pathophysiology and severity of the disease. Interventions that aim to enhance adherence may confer cost-effectiveness benefits in some indications and settings, and good adherence can help payers and providers contain costs by extracting maximum value from their investment in therapies.
Objectives This study sought to investigate abnormalities in coronary circulatory function in 2 different disease entities of obese (OB) and morbidly obese (MOB) individuals and to evaluate whether ...these would differ in severity with different profiles of endocannabinoids, leptin, and C-reactive protein (CRP) plasma levels. Background There is increasing evidence that altered plasma levels of endocannabinoids, leptin, and CRP may affect coronary circulatory function in OB and MOB. Methods Myocardial blood flow (MBF) responses to cold pressor test from rest and during pharmacologically induced hyperemia were measured with N-13 ammonia positron emission tomography/computed tomography. Study participants (n = 111) were divided into 4 groups based on their body mass index (BMI) (kg/m2 ): 1) control group (BMI: 20 to 24.9, n = 30); 2) overweight group (BMI: 25 to 29.9, n = 31), 3) OB group (BMI: 30 to 39.9, n = 25); and 4) MOB group (BMI ≥40, n = 25). Results The cold pressor test–induced change in endothelium-related MBF response (ΔMBF) progressively declined in overweight and OB groups when compared with the control group median: 0.19 (interquartile range IQR 0.08, 0.27) and 0.11 (0.03, 0.17) vs. 0.27 (0.23, 0.38) ml/g/min; p ≤ 0.01, respectively, whereas it did not differ significantly between OB and MOB groups median: 0.11 (IQR: 0.03, 0.17) and 0.09 (–0.01, 0.19) ml/g/min; p = 0.93. Compared with control subjects, hyperemic MBF subjects comparably declined in the overweight, OB, and MOB groups median: 2.40 (IQR 1.92, 2.63) vs. 1.94 (1.65, 2.30), 2.05 (1.67, 2.38), and 2.14 (1.78, 2.76) ml/g/min; p ≤ 0.05, respectively. In OB individuals, ΔMBF was inversely correlated with increase in endocannabinoid anandamide (r = –0.45, p = 0.044), but not with leptin (r = –0.02, p = 0.946) or with CRP (r = –0.33, p = 0.168). Conversely, there was a significant and positive correlation among ΔMBF and elevated leptin (r = 0.43, p = 0.031) and CRP (r = 0.55, p = 0.006), respectively, in MOB individuals that was not observed for endocannabinoid anandamide (r = 0.07, p = 0.740). Conclusions Contrasting associations of altered coronary endothelial function with increases in endocannabinoid anandamide, leptin, and CRP plasma levels identify and characterize OB and MOB as different disease entities affecting coronary circulatory function.
Abstract Objective To evaluate the clinical, methodological and reporting aspects of systematic reviews and meta-analyses in order to determine the efficacy of therapeutic patient education (TPE). ...Methods A thorough search of the medical and nursing literature recorded in MedLine database from 1999 to August 2009 was conducted using the keywords: patient education, efficacy, diabetes, asthma, COPD, hypertension, cardiology, obesity, rheumatology , and oncology. Results Thirty five relevant meta-analyses were identified and initially selected for critical analyses (598 studies concerning approximately 61,000 patients). The detailed description of the educative intervention was present in 4% of articles whereas in 23% the interventions were briefly described. In the majority of studies, the educative interventions were only named (49%) or totally absent (24%). The majority of studies reported improvement of patient outcomes due to the TPE (64%), 30% of studies reported no effect of TPE and 6% of the analysed reviews and meta-analyses reported worsening of measured outcomes. Conclusion Patient education could improve patient outcomes. The high benefit from TPE was shown by articles with detailed description of educational intervention as well as by those who report multidimensional and multidisciplinary educational intervention. Practice implications The impact of therapeutic patient education on health outcomes is 50–80%.
Obesity and the four facets of impulsivity Mobbs, Olivia; Crépin, Christelle; Thiéry, Christelle ...
Patient education and counseling,
06/2010, Volume:
79, Issue:
3
Journal Article, Web Resource
Peer reviewed
Open access
Abstract Objective Obesity is a complex condition involving biological, psychological, sociocultural and environmental components. Impulsivity seems to be a particularly important factor. Whiteside ...and Lynam recently proposed dividing impulsivity into four separate dimensions: Urgency, lack of Premeditation, lack of Perseverance and Sensation Seeking (associated with a tendency to exaggerate the impact of rewards). The objective of this article is to examine how obesity and eating disorder symptoms may be related to the four facets of impulsivity. Methods Whiteside and Lynam's Impulsive Behavior Scale, the Sensitivity to Punishment and Sensitivity to Reward Questionnaire, the Eating Disorder Examination Questionnaire and the Mizes Anorectic Cognitions Questionnaire were used to explore the association between the cognitive and motivational facets of impulsivity and obesity in 47 overweight or obese persons with eating disorders and 47 normal-weight controls. Results Results suggest that overweight and obese persons have higher levels of Urgency, lack of Perseverance and Sensitivity to Reward. Conclusion These results suggest that obese and overweight persons have difficulty inhibiting automatic or dominant behavior and intrusive thoughts and a higher sensitivity to reward. Practice implications Overweight and obese persons may benefit from psychological interventions targeting self-control problems associated with impulsive eating behaviors.
Rimonabant, a selective cannabinoid-1 receptor (CB1) blocker, has been shown to reduce body weight and improve cardiovascular risk factors in obese patients. The Rimonabant in Obesity-Lipids ...(RIO-Lipids) study examined the effects of rimonabant on metabolic risk factors, including adiponectin levels, in high-risk patients who are overweight or obese and have dyslipidemia.
We randomly assigned 1036 overweight or obese patients (body-mass index the weight in kilograms divided by the square of the height in meters, 27 to 40) with untreated dyslipidemia (triglyceride levels >1.69 to 7.90 mmol per liter, or a ratio of cholesterol to high-density lipoprotein HDL cholesterol of >4.5 among women and >5 among men) to double-blinded therapy with either placebo or rimonabant at a dose of 5 mg or 20 mg daily for 12 months in addition to a hypocaloric diet.
The rates of completion of the study were 62.6 percent, 60.3 percent, and 63.9 percent in the placebo group, the group receiving 5 mg of rimonabant, and the group receiving 20 mg of rimonabant, respectively. The most frequent adverse events resulting in discontinuation of the drug were depression, anxiety, and nausea. As compared with placebo, rimonabant at a dose of 20 mg was associated with a significant (P<0.001) mean weight loss (repeated-measures method, -6.7+/-0.5 kg, and last-observation-carried-forward analyses, -5.4+/-0.4 kg), reduction in waist circumference (repeated-measures method, -5.8+/-0.5 cm, and last-observation-carried-forward analyses, -4.7+/-0.5 cm), increase in HDL cholesterol (repeated-measures method, +10.0+/-1.6 percent, and last-observation-carried-forward analyses, +8.1+/-1.5 percent), and reduction in triglycerides (repeated-measures method, -13.0+/-3.5 percent, and last-observation-carried-forward analyses, -12.4+/-3.2 percent). Rimonabant at a dose of 20 mg also resulted in an increase in plasma adiponectin levels (repeated-measures method, 57.7 percent, and last-observation-carried-forward analyses, 46.2 percent; P<0.001), for a change that was partly independent of weight loss alone.
Selective CB1-receptor blockade with rimonabant significantly reduces body weight and waist circumference and improves the profile of several metabolic risk factors in high-risk patients who are overweight or obese and have an atherogenic dyslipidemia.
Using genome-wide data from 253,288 individuals, we identified 697 variants at genome-wide significance that together explained one-fifth of the heritability for adult height. By testing different ...numbers of variants in independent studies, we show that the most strongly associated ∼2,000, ∼3,700 and ∼9,500 SNPs explained ∼21%, ∼24% and ∼29% of phenotypic variance. Furthermore, all common variants together captured 60% of heritability. The 697 variants clustered in 423 loci were enriched for genes, pathways and tissue types known to be involved in growth and together implicated genes and pathways not highlighted in earlier efforts, such as signaling by fibroblast growth factors, WNT/β-catenin and chondroitin sulfate-related genes. We identified several genes and pathways not previously connected with human skeletal growth, including mTOR, osteoglycin and binding of hyaluronic acid. Our results indicate a genetic architecture for human height that is characterized by a very large but finite number (thousands) of causal variants.
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