Effect of semaglutide 2.4 mg on physical functioning and weight- and health-related quality of life in adults with overweight or obesity: Patient-reported outcomes from the STEP 1-4 trials.

AIMS: To summarize the effects of semaglutide 2.4 mg on weight-related quality of life (WRQOL) and health-related quality of life (HRQOL), focusing on the confirmatory secondary endpoint of physical functioning. MATERIALS AND METHODS: The STEP 1-4 Phase 3a, 68-week, double-blind, randomized controlled trials assessed the efficacy and safety of semaglutide 2.4 mg versus placebo in individuals with overweight/obesity. WRQOL and HRQOL were assessed by change from baseline to Week 68 in two different but complementary measures, the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT; STEP 1 and 2) and the SF-36v2 Health Survey Acute (SF-36v2; STEP 1-4). RESULTS: Superiority for semaglutide 2.4 mg over placebo based on IWQOL-Lite-CT and SF-36v2 physical functioning scores was confirmed in STEP 1 and 2 and in STEP 1, 2 and 4, respectively. At Week 68, a greater proportion of participants treated with semaglutide 2.4 mg than with placebo reached meaningful within-person change (MWPC) thresholds for IWQOL-Lite-CT Physical Function scores in STEP 1 (51.8% vs. 28.3%; p < 0.0001) and STEP 2 (39.6% vs. 29.5%; p = 0.0083) and the MWPC threshold for SF-36v2 Physical Functioning in STEP 1 (39.8% vs. 24.1%; p < 0.0001), STEP 2 (41.0% vs. 27.3%; p = 0.0001) and STEP 4 (18.0% vs. 6.6%; p < 0.0001). All other IWQOL-Lite-CT and SF-36v2 scale scores in STEP 1-4 were numerically improved with semaglutide 2.4 mg versus placebo, except for SF-36v2 Role Emotional in STEP 2. CONCLUSIONS: Semaglutide 2.4 mg significantly improved physical functioning, with greater proportions of participants achieving MWPC compared with placebo, and showed beneficial effects on WRQOL and HRQOL beyond physical functioning.

Confirmatory psychometric evaluations of the Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT).

The Impact of Weight on Quality of Life-Lite Clinical Trials Version (IWQOL-Lite-CT) was developed to assess weight-related physical and psychosocial functioning in the context of clinical trials. Data from two pivotal trials of once-weekly subcutaneous semaglutide for the purpose of weight management (NCT03548935 and NCT03552757) were analysed to confirm the structure, reliability, validity, and responsiveness of the IWQOL-Lite-CT and evaluate the magnitude of meaningful within-patient change in patients with overweight or obesity, with and without type 2 diabetes. Factor analyses and inter-item correlations confirmed the IWQOL-Lite-CT structure and scoring algorithm. Each composite score (physical, physical function, psychosocial, and total) demonstrated excellent internal consistency (Cronbach's alphas ≥ 0.82) and test-retest reliability (intraclass correlation coefficients ≥ 0.85) in both trials. Patterns of cross-sectional and longitudinal construct validity correlations were generally consistent with hypotheses. Each of the IWQOL-Lite-CT composites was able to discriminate between known groups. Effect sizes and paired t tests comparing IWQOL-Lite-CT scores at baseline and Week 68 were statistically significant for all composites in both trials (P < 0.0001), providing strong support for the ability to detect change. Results of anchor-based analyses supported responder thresholds ranging from 13.5 to 16.6 across composite scores. The IWQOL-Lite-CT, a comprehensive assessment of weight-related functioning from the patient perspective, is appropriate for use in clinical trials evaluating the efficacy of new treatments for weight management.

Development of the impact of weight on daily activities questionnaire: A patient-reported outcome measure.

While patient-reported outcome measures are available to evaluate health-related quality of life and functioning in obesity, existing measures do not evaluate the impact of excess weight and weight loss on the ability to perform regularly occurring daily activities. Three iterative sets of qualitative interviews were conducted in two countries (United States, n = 23; United Kingdom, n = 23) with individuals with body mass index ≥30 kg/m2 to inform development of the Impact of Weight on Daily Activities Questionnaire (IWDAQ) for use in clinical trials to evaluate daily activity limitations associated with excess weight. Candidate concepts were selected based on the literature, expert opinion, and previously conducted qualitative research, after which the draft IWDAQ was developed and tested. Interviews included a brief concept elicitation phase, followed by cognitive debriefing during which the IWDAQ was refined based upon participants' feedback. The IWDAQ uses a novel, adaptive questionnaire design, such that clinical trial participants choose the three IWDAQ activities they would most like to improve with weight loss and rate the degree of limitation in each of these activities at baseline. By allowing individuals participating in trials to identify and monitor changes in the activities they most want to see improve with weight loss, the 19-item IWDAQ has the potential to detect the benefits of weight-loss treatment that individuals with obesity value most.

Validation of a new measure of quality of life in obesity trials: Impact of Weight on Quality of Life-Lite Clinical Trials Version.

The Impact of Weight on Quality of Life-Lite (IWQOL-Lite) is widely used in evaluations of weight-loss interventions, including pharmaceutical trials. Because this measure was developed using input from individuals undergoing intensive residential treatment, the IWQOL-Lite may include concepts not relevant to clinical trial populations and may be missing concepts that are relevant to these populations. An alternative version, the IWQOL-Lite Clinical Trials Version (IWQOL-Lite-CT), was developed and validated according to the US Food and Drug Administration's (FDA's) guidance on patient-reported outcomes. Psychometric analyses were conducted to validate the IWQOL-Lite-CT using data from two randomized trials (NCT02453711 and NCT02906930) that included individuals with overweight/obesity, with and without type 2 diabetes. Additional measures included the SF-36, global items, weight and body mass index. The IWQOL-Lite-CT is a 20-item measure with two primary domains (Physical [seven items] and Psychosocial [13 items]). A five-item Physical Function composite and Total score were also supported. Cronbach's alpha and intraclass correlation coefficients exceeded 0.77 at each time point; patterns of construct validity correlations were consistent with hypotheses; and scores demonstrated treatment benefit. The IWQOL-Lite-CT is appropriate for assessing weight-related physical and psychosocial functioning in populations commonly targeted for obesity clinical trials. Qualification from the FDA is being sought for use of the IWQOL-Lite-CT in clinical trials to support product approval and labelling claims.

A randomized multifactorial intervention study for prevention of ischaemic heart disease (Inter99): the long-term effect on physical activity.

AIM: To examine the effect of a randomized multiple risk factor intervention study for prevention of ischaemic heart disease (IHD) on the development in physical activity over a 36-month period. METHODS: Two random samples (high intensity intervention, group A, n=11,708; low intensity intervention, group B, n=1,308) were invited for a health examination, an assessment of absolute risk of developing IHD, and an individualized lifestyle intervention. The participation rate was 52.5%. High-risk persons in group A were also offered diet/physical activity and/or smoking cessation group counselling. High-risk persons in group B were referred to their GP. High-risk persons were re-counselled after 12 and 36 months. The control group (group C, n=5,264, response rate=61.3%) answered a mailed questionnaire. Data were analysed using longitudinal linear regression models with random effects. MAIN OUTCOME: Change in physical activity from baseline to 12-and 36-month follow-up. RESULTS: In men, the high-intensity (group A) intervention had a beneficial effect at 12-month follow-up, whereas after 36 months both the high-intensity and the low-intensity (group B) intervention had a beneficial effect on the development in physical activity when compared with group C. This was regardless of baseline physical activity level. At 36-month follow-up there was no significant difference between groups A and B. There was no intervention effect among women. CONCLUSIONS: Only men seemed to benefit from the intervention.

High risk strategy in smoking cessation is feasible on a population-based level. The Inter99 study.

INTRODUCTION: A high risk strategy is one of more strategies in public health. Smoking remains the most important contributor to the burden of disease in developed countries. METHODS: A population-based multi-factorial intervention study, Inter99 (1999-2006), Copenhagen, Denmark, using a high risk strategy. All 2408 daily smokers were repeatedly offered individual face-to-face lifestyle counselling. Smokers in the high-intensity group were offered participation in smoking cessation groups. We measured point abstinence at 1, 3 and 5-year follow-up and compared with a control group, using adjusted intention-to treat analyses. RESULTS: Compared with the control group it was twice as likely to be self-reported abstinent at 5-year follow-up in the high-intensity intervention group (OR: 2.19; 95%CI: 1.7-2.8; p<0.001). The effect of the intervention was significant, even when comparing validated abstinence in the intervention groups with self-reported abstinence in the control group (OR: 1.38; 95%CI: 1.1-1.8; p=0.014). Male gender, vocational training, higher age at onset of smoking, high knowledge of harm of smoking and lower tobacco consumption predicted abstinence. CONCLUSION: A high risk strategy showed a significant effect on smoking in the long term. Proactive recruitment, face-to-face setting, repeated offer of assistance to quit and a multi-factorial approach may explain the success of the intervention.

Commuting physical activity is favourably associated with biological risk factors for cardiovascular disease.

BACKGROUND: Little is known about the effects of commuting physical activity on biological cardiovascular risk factors although such knowledge may form an important basis for interventions aimed at reducing cardiovascular disease (CVD) by increasing physical activity. We examined the associations between commuting, leisure time and total physical activity and biological risk factors for CVD. Design A cross-sectional study of men and women, who participated in a health screening programme. METHODS: The study population comprised persons aged 30-60 years from a population-based random sample, response rate 53% (n = 6,906). Weight, height, waist circumference and blood pressure were measured and blood samples were collected. Physical activity was assessed by a self-administered questionnaire. RESULTS: Time spent on commuting, leisure time and total physical activity was positively associated with high-density lipoprotein cholesterol and negatively associated with low-density lipoprotein cholesterol, triglycerides, waist circumference and body mass index. Time spent on total physical activity was negatively associated with total cholesterol and diastolic blood pressure. Among men there was no relationship between time spent on physical activity and systolic blood pressure. Time spent on commuting physical activity and total physical activity was negatively associated with systolic blood pressure among women. CONCLUSION: Commuting physical activity, independent of leisure time physical activity, was associated with a healthier level of most of the cardiovascular risk factors. An increase in commuting physical activity in the population may therefore reduce the incidence of CVD.

Diet and exercise intervention in a general population--mediators of participation and adherence: the Inter99 study.

BACKGROUND: Drop-out rates are high in many lifestyle programmes. To promote adherence, the aim of this study was to identify mediators of participation in a diet and exercise (DE) intervention in a general population. METHODS: Data were baseline data from a randomized non-pharmacological clinical trial in Copenhagen during 1999-2001. The participation rate was 53.3%. Participants at high risk of ischaemic heart disease (IHD) and who were offered participation in a DE counselling group intervention were included (N = 2022). Clinical characteristics, and demographic, psychosocial and lifestyle factors were measured. RESULTS: Mediators of acceptance of participation were awareness of an unhealthy lifestyle or a bad health, low self-rated care of own health, perceived susceptibility of cardiovascular disease (CVD; overall and associated with lifestyle), high degree of motivation towards dietary changes and low self-efficacy about increasing physical activity. Overweight and impaired glucose tolerance (IGT)/screen-detected diabetes predicted acceptance whereas an absolute risk score for IHD was inverse associated with acceptance. Mediators of high adherence were low self-efficacy about changing dietary habits and perceived susceptibility of CVD and furthermore screen-detected diabetes and overweight predicted high adherence. CONCLUSION: Awareness of unhealthy lifestyle, perceived susceptibility of disease and motivation towards lifestyle changes were important mediators of participation. Screen-detected diabetes/IGT predicted participation and adherence whereas overweight individuals were more likely to accept but also to drop out of the course. The use of an absolute risk score in health promotion should be further evaluated.