Early use of oral semaglutide in the UK: A cost-effectiveness analysis versus continuing metformin and SGLT-2 inhibitor therapy.

OBJECTIVES: Many people with type 2 diabetes experience clinical inertia, remaining in poor glycaemic control on oral glucose-lowering medications rather than intensifying treatment with a glucagon-like peptide-1 receptor agonist, despite an efficacious, orally administered option, oral semaglutide, being available. The present study evaluated the long-term cost-effectiveness of initiating oral semaglutide versus continuing metformin plus sodium-glucose cotransporter-2 (SGLT-2) inhibitor therapy in the UK. DESIGN: Outcomes were projected over patients' lifetimes using the IQVIA Core Diabetes Model (V.9.0). Clinical data were taken from the oral semaglutide and placebo arms of the patient subgroup receiving metformin plus an SGLT-2 inhibitor in PIONEER 4. Costs, expressed in 2021 Pounds sterling (GBP), were accounted from a healthcare payer perspective. INTERVENTIONS: Modelled patients received oral semaglutide immediately (in the first year of the analysis) or after a 2-year delay, after which all physiological parameters were brought to values observed in the immediate therapy arm. During the simulation, patients intensified with the addition of basal insulin and, subsequently, by switching to basal-bolus insulin. RESULTS: Immediate oral semaglutide therapy was associated with improvements in life expectancy of 0.17 (95% CIs 0.16 to 0.19) years, and quality-adjusted life expectancy of 0.15 (0.14 to 0.16) quality-adjusted life years (QALYs), versus a 2-year delay. Benefits were due to a reduced incidence of diabetes-related complications. Direct costs were estimated to be GBP 1423 (1349 to 1496) higher with immediate oral semaglutide therapy versus a 2-year delay, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Immediate oral semaglutide therapy was therefore associated with an incremental cost-effectiveness ratio of GBP 9404 (8380 to 10 538) per QALY gained versus a 2-year delay. CONCLUSIONS: Immediate oral semaglutide is likely to represent a cost-effective treatment in people with type 2 diabetes with inadequate glycaemic control on metformin plus an SGLT-2 inhibitor in the UK. TRIAL REGISTRATION NUMBER: NCT02863419.

Calibration of the IQVIA Core Diabetes Model to the stroke outcomes from the SUSTAIN 6 cardiovascular outcomes trial of once-weekly semaglutide.

AIMS: In the SUSTAIN 6 cardiovascular outcomes trial, once-weekly semaglutide was associated with a statistically significant reduction in major adverse cardiovascular events compared with placebo. To date, no studies have assessed how accurately existing diabetes models predict the outcomes observed in SUSTAIN 6. The aims of this analysis were to investigate the performance of the IQVIA Core Diabetes Model when used to predict the SUSTAIN 6 trial outcomes, to calibrate the model such that projected outcomes reflected observed outcomes, and to examine the impact of calibration on the cost-effectiveness of once-weekly semaglutide from a UK healthcare payer perspective. METHODS: The IQVIA Core Diabetes Model was calibrated to ensure that the projected non-fatal stroke event rates reflected the non-fatal stroke event rates observed in SUSTAIN 6 over a two-year time horizon. Cost-effectiveness analyses of once-weekly semaglutide versus placebo plus standard of care were conducted over a lifetime horizon using the uncalibrated and calibrated models to assess the impact on cost-effectiveness outcomes. RESULTS: To replicate the non-fatal stroke event rate in SUSTAIN 6, calibration of the model through the application of relative risks for stroke of 1.07 and 1.65 with once-weekly semaglutide and placebo, respectively, was required. In the long-term cost-effectiveness analysis, the uncalibrated model projected an incremental cost-effectiveness ratio for once-weekly semaglutide versus placebo plus standard of care of GBP 22,262 per quality-adjusted life year (QALY) gained, which fell to GBP 17,594 per QALY gained when the calibrated model was used. CONCLUSIONS: The requirement for calibration to replicate the outcomes observed in SUSTAIN 6 suggests that the reductions in risk of cardiovascular complications observed with once-weekly semaglutide cannot be solely explained by differences in conventional risk factors. Accurate estimation of the risk of diabetes-related complications using methods such as calibration is important to ensure accurate cost-effectiveness analyses are conducted.

Evaluating the Long-Term Cost-Effectiveness of Once-Weekly Semaglutide 1 mg Versus Liraglutide 1.8 mg: A Health Economic Analysis in the UK.

INTRODUCTION: Glucagon-like peptide-1 (GLP-1) receptor agonists represent highly efficacious treatment options for type 2 diabetes. Liraglutide was amongst the first authorised for use in 2010, but once-weekly semaglutide represents the most efficacious GLP-1 analogue currently available for type 2 diabetes. The aim of the present analysis was therefore to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus liraglutide 1.8 mg with a lowered acquisition cost in the UK, as potentially lower cost liraglutide formulations may soon be developed. METHODS: Outcomes were projected over patients' lifetimes using the IQVIA Core Diabetes Model (v9.0). Baseline cohort characteristics were sourced from SUSTAIN 2, with changes in HbA1c, blood pressure and body mass index applied from a network meta-analysis, in which SUSTAIN 2 was used to inform the semaglutide arm. Modelled patients received semaglutide or liraglutide for 3 years, after which treatment was intensified to basal insulin. Costs were accounted from a healthcare payer perspective and expressed in 2021 pounds sterling (GBP). The acquisition cost of liraglutide was reduced by 33% compared with the currently marketed formulation. RESULTS: Life expectancy and quality-adjusted life expectancy were projected to improve with once-weekly semaglutide 1 mg, by 0.05 years and 0.06 quality-adjusted life years, respectively, versus liraglutide 1.8 mg. Clinical benefits were due to a reduced incidence of diabetes-related complications with semaglutide. Direct costs were estimated to be GBP 280 lower with semaglutide, entirely because of avoidance of diabetes-related complications versus liraglutide. Semaglutide 1 mg was therefore considered dominant versus liraglutide 1.8 mg, even with the liraglutide price reduced by 33%. CONCLUSION: Once-weekly semaglutide 1 mg is likely to represent a dominant treatment option versus liraglutide 1.8 mg for the treatment of type 2 diabetes in the UK, even with the liraglutide price reduced by 33%.

Once-weekly semaglutide versus insulin aspart for the treatment of type 2 diabetes in the UK: A long-term cost-effectiveness analysis based on SUSTAIN 11.

AIM: To evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus insulin aspart in the UK. MATERIALS AND METHODS: Long-term outcomes were projected over patients' lifetimes using the IQVIA CORE Diabetes Model (vers 9.0). SUSTAIN 11 was used to inform baseline cohort characteristics and treatment effects. Patients were modelled to receive once-weekly semaglutide plus basal insulin for 3 years before intensifying to basal-bolus insulin, compared with basal-bolus insulin for lifetimes in the aspart arm. Costs were accounted from a healthcare payer perspective in the UK, expressed in 2021 pounds sterling (GBP). RESULTS: Once-weekly semaglutide 1 mg was associated with improvements in quality-adjusted life expectancy of 0.18 quality-adjusted life years (QALYs) versus insulin aspart, due to a reduced incidence and delayed time to onset of diabetes-related complications. Direct costs were estimated to be GBP 800 higher with semaglutide, with higher treatment costs partially offset by cost savings from avoidance of diabetes-related complications. Once-weekly semaglutide 1 mg was therefore associated with an incremental cost-effectiveness ratio of GBP 4457 per QALY gained versus insulin aspart. CONCLUSIONS: Based on a willingness-to-pay threshold of GBP 20 000 per QALY gained, once-weekly semaglutide 1 mg was projected to be highly cost-effective versus insulin aspart for the treatment of type 2 diabetes in the UK.

The challenges and pitfalls of incorporating evidence from cardiovascular outcomes trials in health economic modelling of type 2 diabetes.

The clinical evidence base for evaluating modern type 2 diabetes interventions has expanded greatly in recent years, with numerous efficacious treatment options available (including dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter-2 inhibitors). The cardiovascular safety of these interventions has been assessed individually versus placebo in numerous cardiovascular outcomes trials (CVOTs), statistically powered to detect differences in a composite endpoint of major adverse cardiovascular events. There have been growing calls to incorporate these data in the long-term modelling of type 2 diabetes interventions because current diabetes models were developed prior to the conduct of the CVOTs and therefore rely on risk equations developed in the absence of these data. However, there are numerous challenges and pitfalls to avoid when using data from CVOTs. The primary concerns are around the heterogeneity of the trials, which have different study durations, inclusion criteria, rescue medication protocols and endpoint definitions; this results in significant uncertainty when comparing two or more interventions evaluated in separate CVOTs, as robust adjustment for these differences is difficult. Analyses using CVOT data inappropriately can dilute clear evidence from head-to-head clinical trials, and blur healthcare decision making. Calibration of existing models may represent an approach to incorporating CVOT data into diabetes modelling, but this can only offer a valid comparison of one intervention versus placebo based on a single CVOT. Ideally, model development should utilize patient-level data from CVOTs to prepare novel risk equations that can better model modern therapies for type 2 diabetes.

The long-term cost-effectiveness of once-weekly semaglutide 1 mg vs. dulaglutide 3 mg and 4.5 mg in the UK.

AIMS: Once-weekly semaglutide and dulaglutide represent two highly efficacious treatment options for type 2 diabetes. A recent indirect treatment comparison (ITC) has associated semaglutide 1 mg with similar and greater improvements in glycated haemoglobin (HbA1c) and body weight, respectively, vs. dulaglutide 3 mg and 4.5 mg. The present study aimed to evaluate the long-term cost-effectiveness of semaglutide 1 mg vs. dulaglutide 3 mg and 4.5 mg in the UK. MATERIALS AND METHODS: The IQVIA CORE Diabetes Model (v9.0) was used to project outcomes over patients' lifetimes. Baseline cohort characteristics were sourced from SUSTAIN 7, with changes in HbA1c and body mass index applied as per the ITC. Modelled patients received semaglutide or dulaglutide for 3 years, after which treatment was intensified to basal insulin. Costs (expressed in 2020 pounds sterling [GBP]) were accounted from a healthcare payer perspective. RESULTS: Semaglutide 1 mg was associated with improvements in quality-adjusted life expectancy of 0.05 and 0.04 quality-adjusted life years (QALYs) vs. dulaglutide 3 mg and 4.5 mg, respectively, due to a reduced incidence of diabetes-related complications with semaglutide. Direct costs were estimated to be GBP 76 lower and GBP 8 higher in the comparisons with dulaglutide 3 mg and 4.5 mg, respectively. Overall outcomes were similar, but favoured semaglutide, and based on modelled mean outcomes it was considered dominant vs. dulaglutide 3 mg and associated with an incremental cost-effectiveness ratio of GBP 228 per QALY gained vs. dulaglutide 4.5 mg. CONCLUSIONS: Semaglutide 1 mg represents a cost-effective treatment vs. dulaglutide 3 mg and 4.5 mg for type 2 diabetes from a healthcare payer perspective in the UK.