The company presented cost-effectiveness estimates for semaglutide in comparison with diet plus exercise for people with a BMI of 30 kg/m2 or more with at least 1 weight-related comorbidity (company's original target population; see section 3.4). For this population, the company's base-case ICER was £14,827 per QALY gained and the ERG's base-case ICER was £16,337 per QALY gained. In STEP 1, 60% of people had a BMI of at least 35.0 kg/m2 and 33% had a BMI of 30.0 kg/m2 to 34.9 kg/m2, and the average BMI was 37.9 kg/m2 (see section 3.6). The company's original target population made up 75% of the STEP 1 trial population (see section 3.6). The committee questioned whether this population in the trial represented the population who, in practice, would be eligible for treatment if the company's original target population were to be recommended. This was because, in the general population, the prevalence of a BMI between 30.0 kg/m2 and 34.9 kg/m2 far exceeded that of a BMI of at least 35.0 kg/m2. In the trial and the modelled population, it was a smaller percentage (see section 3.2). Scenario analyses done by the ERG showed that, if the mean starting BMI was 32.5 kg/m2, the ICER increased from the base case of £16,337 per QALY gained (including a mean starting BMI of 38.7 kg/m2) to £22,192 per QALY gained. Therefore, expanding the population to include large numbers with a lower BMI would increase the ICER. There was additional underlying uncertainty related to model inputs. This included the time to losing the weight advantage associated with semaglutide (see section 3.13), and the percentage of people with type 2 diabetes who would have treatment in practice (see section 3.7). The ERG's scenario analysis assuming a loss of weight advantage over 2 years rather than 3 years increased the ICER to £21,060 per QALY gained. The company's scenario analysis including people with type 2 diabetes in the model increased the ICER to £21,277 per QALY gained. The committee also discussed the concern about the reliability of using risk equations to predict cardiovascular events. It noted that these were predictions alone and not based on clinical evidence (see section 3.16). However, although this remained an uncertainty, semaglutide was still cost effective if these benefits were not included in the model. It also discussed that only providing semaglutide for a maximum of 2 years was not ideal for treating a chronic condition (see section 3.12). It noted that the ICER increased when treatment duration was increased in the model because of a plateauing of the benefits seen with semaglutide. The committee was aware that referral to specialist weight management services for people with a BMI of less than 35.0 kg/m2 is only made in specific circumstances. Also, according to 1 clinical expert, the population of people with a BMI of less than 35.0 kg/m2 in tier 3 services is 1.5% (see section 3.2). There would therefore be big implications for NHS service delivery if the population were to be significantly expanded as in the company's original target population. The committee considered that it therefore needed to have a high level of confidence that this was a cost-effective strategy for the NHS. Given the high level of uncertainty, the committee agreed that it was appropriate to consider a population at the highest risk for the adverse effects of obesity and likely to gain the most benefit from semaglutide. This would increase the likelihood of semaglutide being a cost-effective treatment. Therefore, the committee concluded that it was appropriate to consider the company's original target population for treatment with semaglutide. But this was only if they also meet the criteria for treatment in specialist weight management services in line with the criteria in NICE's guideline on obesity.