TA875 · STA
Semaglutide is recommended as part of specialist weight management services for a maximum of 2 years for adults with at least 1 weight-related comorbidity and either: a BMI of at least 35.0 kg/m2, or a BMI of 30.0-34.9 kg/m2 and meeting criteria for referral to specialist weight management services. Lower BMI thresholds (usually reduced by 2.5 kg/m2) should be used for people from south Asian, Chinese, and Black African or Caribbean family backgrounds. Consider stopping if less than 5% initial weight loss achieved after 6 months of maintenance dose.
Source documents
Intervention
Conditions
Comparators
| Name | Type | Established | Committee preferred |
|---|---|---|---|
| weight management support, diet and exercise | best supportive care | Yes | — |
| liraglutide plus weight management support, diet and exercise | active drug | Yes | — |
| liraglutide | active drug | Yes | — |
| diet and exercise | best supportive care | — | — |
Clinical trials
| Trial | Design | Phase | Pivotal |
|---|---|---|---|
| STEP 1 | RCT | Phase 3 | Yes |
| STEP 2 | RCT | — | — |
| SCALE 1839 | RCT | — | — |
| STEP 8 | RCT | — | — |
| STEP 4 | RCT | Phase 3 | — |
| STEP 5 | RCT | Phase 3 | — |
| SELECT | RCT | — | — |
Economic model
ICER
Methodological decisions (22)
Choice between diet/exercise alone vs liraglutide comparator depending on population
Company: Proposed diet and exercise as comparator; liraglutide not relevant for broader population
Committee: Diet and exercise for BMI ≥30 with comorbidity; liraglutide plus support for BMI ≥35 with non-diabetic hyperglycaemia and cardiovascular risk
ICER impact: uncertain_direction
The committee agreed that specialist weight management services with multidisciplinary lifestyle interventions are the only appropriate setting for semaglutide treatment. It rejected the suggestion that semaglutide could be offered in tier 2 services or mental health services, as these settings could not provide the necessary multidisciplinary specialist interventions required by the marketing authorisation.
Committee: Semaglutide should only be delivered as part of specialist weight management services (tier 3) alongside a sustained programme of multidisciplinary lifestyle interventions, in line with marketing authorisation and trial design.
ICER impact: uncertain_direction
Annual cost of sleep apnoea treatment
Company: £1,081 per year
ERG: £274 per year
Committee: ERG's lower estimate accepted as reasonable
ICER impact: negligible
Comparison between semaglutide (STEP 1) and liraglutide (SCALE 1839) for the liraglutide-eligible subgroup (BMI ≥35 kg/m² with non-diabetic hyperglycaemia and high CV risk). Head-to-head STEP 8 trial later provided direct evidence.
Company: Indirect treatment comparison using individual patient data from STEP 1 and SCALE 1839 was appropriate. Later, direct head-to-head data from STEP 8 (full trial population, not subgroup-specific) was submitted.
ERG: Direct trial evidence for the liraglutide-eligible subgroup would have been preferred. The results in STEP 8 were for the full trial population, not the liraglutide-eligible subgroup.
Committee: Direct trial evidence for the subgroup would have been preferred. However, agreed that both the indirect treatment comparison and full population results from STEP 8 showed semaglutide is more effective than liraglutide for weight loss.
ICER impact: negligible
Company's cohort-transition model with 11 health states based on previous liraglutide appraisal model. Model only allowed up to 3 years of treatment. Transitions based on type 2 diabetes status and cardiovascular events estimated from risk equations.
Committee: Expressed concern about the validity of risk equations used for transitions. However, concluded that the perspective of use in specialist weight management services was appropriate and the model was suitable for decision making.
ICER impact: uncertain_direction
The committee discussed that while the model captured long-term benefits of weight loss, some long-term benefits such as reduced risk of liver disease may not have been captured. Additionally, the model may not have captured benefits including reduced risk of COVID-19-related adverse events, reduction in social isolation and stigma, and improved fertility/IVF success rates.
Committee: The committee concluded it was important to consider these uncounted benefits, which may positively affect cost-effectiveness estimates if modelled, despite uncertainty around model assumptions.
ICER impact: uncertain_direction
Whether all people with non-diabetic hyperglycaemia develop type 2 diabetes after cardiovascular event
Company: All people with non-diabetic hyperglycaemia who have a cardiovascular event develop type 2 diabetes within following year
ERG: Removed this assumption; scenario analysis had minimal effect on ICER
Committee: True proportion falls between none and all; ERG's more conservative approach accepted
ICER impact: negligible
Natural weight change assumptions by age
Company: Weight increases 0.46 kg per year, remains constant after age 68
ERG: Weight increases 0.30 kg per year, then decreases 0.30 kg after age 66
Committee: Both approaches are reasonable with minimal differential effect on ICER
ICER impact: negligible
STEP 1 trial population BMI distribution (61.2% BMI ≥35 kg/m²) does not reflect general population distribution of overweight and obesity
Company: Presented evidence for BMI ≥30 kg/m² with comorbidities and separately for BMI ≥35 kg/m² with specific risk factors
Committee: Population identified with highest risk for adverse effects of obesity, focusing on BMI ≥35 kg/m² and those meeting tier 3 specialist service criteria
ICER impact: uncertain_direction
The population in STEP 1 has a larger proportion of people with BMI ≥35 kg/m² (61.2%) compared to the general population where BMI 30-35 kg/m² is more prevalent. Average BMI in trial was 37.9 kg/m² versus likely lower average in treated population.
Company: Target population is BMI ≥30 kg/m² with at least 1 weight-related comorbidity (75% of STEP 1). This should be considered eligible for semaglutide.
Committee: The population in STEP 1 did not reflect the population distribution of overweight and obesity in the general population. A larger proportion of the trial had higher BMI (35+ kg/m²), which does not match what would likely be treated if broader eligibility were accepted. The trial population was unlikely to correspond with the distribution of people who could be eligible if the company's original target population was recommended.
ICER impact: increases
STEP 1 excluded people with type 2 diabetes, although they could be offered semaglutide for weight management in specialist services. Clinical experts expected people with type 2 diabetes to have less weight loss with semaglutide than seen in STEP 1 (supported by STEP 2 data).
Committee: STEP 1 did not cover the whole population who would potentially be offered semaglutide in the NHS. This introduced uncertainty about the generalisability of clinical effectiveness and may have affected the reliability of cost-effectiveness results.
ICER impact: uncertain_direction
Generalisability of STEP 1 trial population (BMI ≥30 with weight-related comorbidity) to NHS practice
Company: Company's original target population (BMI ≥30 with comorbidity) represents achievable NHS population
ERG: Scenario analysis showed mean BMI of 32.5 kg/m² would increase ICER to £22,192 per QALY
Committee: Population should be restricted to those meeting both original criteria AND specialist weight management service eligibility criteria per NICE obesity guidelines
ICER impact: increases
Committee considered whether the trial population was representative of the company's original target population. There was uncertainty about whether the trial population accurately reflected those with BMI <35.0 kg/m2 in tier 3 services (estimated at only 1.5% of the population). The committee noted this created high levels of uncertainty regarding cost-effectiveness in the broader target population.
Committee: The committee required a high level of confidence in cost-effectiveness given the implications for NHS service delivery if the population were significantly expanded. They concluded the company's original target population was appropriate but only if patients also meet NICE's clinical guideline criteria for specialist weight management services.
ICER impact: uncertain_direction
Company included a stopping rule for people with less than 5% weight loss after 6 months, based on marketing authorisation guidance to reassess benefit at 6 months.
Company: Stopping rule of <5% weight loss at 6 months is appropriate and based on the marketing authorisation.
Committee: It is reasonable to assume that people stop treatment after 6 months if they do not have an adequate response. This is in line with the marketing authorisation and clinical practice expectations.
ICER impact: negligible
Whether people without at least 5% weight loss at 6 months should continue treatment
Company: Stopping rule applied: people without at least 5% weight loss at 6 months are stopped
ERG: Stopping rule applied
Committee: Agreed stopping rule is reasonable in line with clinical evidence and practice
ICER impact: negligible
Use of risk equations to model long-term cardiovascular and diabetes outcomes
Company: Risk equations used to estimate long-term cardiovascular events and type 2 diabetes risk based on STEP 1 surrogate outcomes
ERG: Risk equations only practical alternative; scenario analyses excluding cardiovascular benefits had small upward effect; excluding diabetes benefits had larger effect
Committee: Risk equations are only method available despite uncertainties; benefits of prolonging time without diabetes are striking and important
ICER impact: decreases
Company included assumption that people would take semaglutide for maximum 2 years. Debate about whether this reflects NHS specialist weight management services (time-limited) versus the chronic nature of obesity.
Company: 2-year treatment limitation is appropriate, aligned with clinical trial evidence (STEP 5) and NHS specialist weight management services duration.
ERG: Longer-term modelling (lifelong use) was not possible in the company model. Increasing treatment duration to 3 years increased the ICER.
Committee: The 2-year assumption is reasonable in the context of NHS specialist weight management services, which are time-limited. However, when further evidence becomes available, long-term or lifetime use in other settings could be considered if clinically and cost-effective. No evidence currently available for longer-term use beyond 2 years.
ICER impact: increases
Maximum treatment duration modelled
Company: Treatment duration capped at 2 years, reflecting clinical trial evidence and NHS specialist weight management service availability
ERG: Agreed 2-year cap is reasonable
Committee: 2-year treatment duration is reasonable in context of NHS specialist weight management services, which are time-limited
ICER impact: increases
Company assumed that 3 years after stopping semaglutide (2-year treatment period), the weight advantage would be completely lost. Also assumed that normoglycaemia would revert to non-diabetic hyperglycaemia 3 years after stopping treatment.
Company: 3-year timeline for complete weight regain after 2-year treatment.
ERG: STEP 4 trial data suggested that not all weight lost is regained 1 year after stopping semaglutide.
Committee: Assumptions around the rate of weight gain after treatment are very uncertain. Clinical experts expected weight advantage to be lost around 2-3 years after stopping, but some people would maintain clinically relevant weight loss for longer. Because semaglutide causes greater weight loss than liraglutide, the time to regain weight would be longer for semaglutide than liraglutide.
ICER impact: uncertain_direction
Rate and timing of weight regain after semaglutide cessation
Company: Weight advantage lost 3 years after stopping treatment; glucose tolerance normalisation reverts within 3 years
ERG: 3-year weight regain assumption is reasonable; scenario analysis with 2-year regain had modest effect
Committee: Uncertain area; 3-year assumption accepted but 2-year alternative also reasonable, with minimal effect on ICER
ICER impact: increases
Semaglutide should only be used within specialist weight management services (tiers 3 and 4) alongside supervised dietary, physical activity and behaviour change interventions, not as stand-alone treatment
Company: Proposed broader population eligibility but agreed acceptable to restrict to those receiving specialist services
Committee: Semaglutide use restricted to specialist weight management settings with multidisciplinary support
ICER impact: uncertain_direction
Whether retreatment with semaglutide after weight regain is modelled
Company: No retreatment modelled
ERG: Not explicitly stated but appears to accept no retreatment in base case
Committee: Retreatment not modelled but acknowledged as potentially appropriate for some people meeting re-referral criteria
ICER impact: uncertain_direction
Evidence gaps
Commercial arrangement
Special considerations
Cross-references