Background Obesity and overweight are major risk factors for several chronic diseases. There is limited systematic evaluation of risk equations that predict the likelihood of developing an obesity or overweight associated complication. Predicting future risk is essential for health economic modelling. Availability of future treatments rests upon a model’s ability to inform clinical and decision-making bodies.  This systematic literature review aimed to identify studies reporting (1) equations that calculate the risk for individuals with obesity, or overweight with a weight-related complication (OWRC), of developing additional complications, namely T2D, cardiovascular (CV) disease (CVD), acute coronary syndrome, stroke, musculoskeletal disorders, knee replacement/arthroplasty, or obstructive sleep apnea; (2) absolute or proportional risk for individuals with severe obesity, obesity or OWRC developing T2D, a CV event or mortality from knee surgery, stroke, or an acute CV event. Methods Databases (MEDLINE and Embase) were searched for English language reports of population-based cohort analyses or large-scale studies in Australia, Canada, Europe, the UK, and the USA between January 1, 2011, and March 29, 2021. Included reports were quality assessed using an adapted version of the Newcastle Ottawa Scale. Results Of the 60 included studies, the majority used European cohorts. Twenty-nine reported a risk prediction equation for developing an additional complication. The most common risk prediction equations were logistic regression models that did not differentiate between body mass index (BMI) groups (particularly above 40 kg/m2) and lacked external validation. The remaining included studies (31 studies) reported the absolute or proportional risk of mortality (29 studies), or the risk of developing T2D in a population with obesity and with prediabetes or normal glucose tolerance (NGT) (three studies), or a CV event in populations with severe obesity with NGT or T2D (three studies). Most reported proportional risk, predominantly a hazard ratio. Conclusion More work is needed to develop and validate these risk equations, specifically in non-European cohorts and that distinguish between BMI class II and III obesity. New data or adjustment of the current risk equations by calibration would allow for more accurate decision making at an individual and population level.

OBJECTIVES: This study assessed the cost-effectiveness of once-weekly semaglutide 2.4mg injection as adjunct to reduced-calorie meals and increased physical activity (diet and exercise, D&E), in adult patients with obesity (body mass index [BMI] of ≥30 kg/m2) or overweight (BMI 27-30 kg/m2) in the presence of ≥1 weight-related comorbidity, by comparing it with D&E alone or D&E in combination with liraglutide 3.0mg, orlistat, or naltrexone 32mg/bupropion (NB32). METHODS: The safety and efficacy of semaglutide 2.4mg and D&E were sourced from the STEP 1 and STEP 2 trials, while a network meta-analysis informed the relative efficacy vs. other comparators. The Core Obesity Model was used to extrapolate costs and health outcomes (both discounted at 1.5% annually) over 40 years for a cohort with starting age 50 years and starting BMI 37.5 kg/m2, taking D&E alone or in combination with other pharmacotherapies for 1 year. Costs were analyzed from a societal perspective, including publicly and privately funded health expenses, patient co-payments, and indirect costs. RESULTS: Semaglutide 2.4mg reduced weight and reverted prediabetes prevalence more than alternative therapies. This translated into delays in the occurrence of weight-related complications, and gains in life-expectancy between 0.081 years vs. D&E (maximum gain) and 0.030 years vs. liraglutide 3.0mg (minimum gain), and quality-adjusted life-years (QALYs) between 0.103 vs. D&E and 0.039 vs. liraglutide 3.0mg, at additional costs. The incremental cost-utility ratios were 29,677 Canadian dollars (CAD)/QALY gained vs. D&E, CAD12,369/QALY gained vs. liraglutide 3.0mg, CAD25,663/QALY gained vs. orlistat and CAD25,003/QALY gained vs. NB32. The cost-effectiveness acceptability curve showed a high likelihood of subcutaneous semaglutide 2.4 mg injection being considered cost-effective, at willingness-to-pay thresholds of CAD50,000/QALY and beyond. CONCLUSION: Based on this analysis, the use of semaglutide 2.4mg injection can be considered a cost-effective alternative compared with D&E alone, or D&E in combination with other pharmacotherapies.

Aim To assess health utility values in the Semaglutide Treatment Effect in People with obesity (STEP) 1‐4 trials. 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 a body mass index (BMI) of 30 kg/m2 or higher or a BMI of 27 kg/m2 or higher and at least one comorbidity (STEP 1, 3 and 4), or a BMI of 27 kg/m2 or higher and type 2 diabetes (STEP 2). Patients received lifestyle intervention plus intensive behavioural therapy in STEP 3. Health‐related quality of life was assessed using the Short Form 36‐item Health Survey version 2 (SF‐36v2) at baseline and week 68. Scores were converted into Short Form Six‐Dimension version 2 (SF‐6Dv2) utility scores or mapped onto the European Quality of Life Five‐Dimension Three‐Level (EQ‐5D‐3L) utility index using UK health utility weights. Results At week 68, semaglutide 2.4 mg was associated with minor health utility score improvements from baseline (all trials), while scores for placebo typically decreased. SF‐6Dv2 treatment differences by week 68 for semaglutide 2.4 mg versus placebo were significant in STEP 1 and 4 (P ≤ .001), but not STEP 2 or 3. EQ‐5D‐3L treatment differences by week 68 for semaglutide 2.4 mg versus placebo were significant in STEP 1, 2 and 4 (P < .001 for all), but not STEP 3. Conclusions Semaglutide 2.4 mg was associated with improvement in health utility scores compared with placebo, reaching statistical significance in STEP 1, 2 and 4.

Purpose The correlation between body mass index (BMI) and utility in patients with overweight or obesity was assessed using health-related quality of life (HRQoL) data collected in two weight-loss interventional studies, SCALE and STEP 1. Methods Short-Form Health Survey 36-Item (SF-36) scores from SCALE and STEP 1 were mapped to EuroQoL-5 dimensions-3 levels (EQ-5D-3L) using an established algorithm to derive utilities for the UK. SF-36 scores from STEP 1 were converted into Short-Form six-dimensions (SF-6D) utilities for Portugal, using the tool developed by the University of Sheffield. Correlations between utility scores and BMI at baseline were assessed by multiple linear regression analyses, controlling for demographic and clinical parameters. Results Higher baseline BMI was correlated with lower EQ-5D-3L/SF-6D utilities in all analyses, although the correlation was nonsignificant. Assuming linearity between BMI ranges 30–40 kg/m2, a unit increase predicted a utility loss of − 0.0041 and − 0.0031 on EQ-5D-3L for males and females, respectively, in SCALE, − 0.0039 and − 0.0047 in STEP 1, and − 0.0027 and − 0.002 on SF-6D males and females, respectively. Presence of hypertension and older age were significantly negatively correlated with SCALE EQ-5D-3L. Age, presence of coronary artery diseases (CADs) and previous smoking were significantly negatively correlated with STEP 1 EQ-5D-3L. Only presence of CADs was significantly negatively correlated with STEP 1 SF-6D. Males had significantly higher utilities compared with females in the UK analyses. Conclusion These findings are useful to inform cost-effectiveness analyses in obesity whereby multiple factors, along with BMI, are used to calculate quality-adjusted life-years.