Dataset Information

Management of Patients with Type 2 Diabetes with Once-Weekly Semaglutide Versus Dulaglutide, Exenatide ER, Liraglutide and Lixisenatide: A Cost-Effectiveness Analysis in the Danish Setting.

ABSTRACT:

Introduction

Once-weekly semaglutide is a novel glucagon-like peptide-1 (GLP-1) analog for the treatment of type 2 diabetes (T2D) that has been associated with greater reductions in glycated hemoglobin (HbA1c) and body weight versus GLP-1 receptor agonists dulaglutide, exenatide extended-release (ER), liraglutide and lixisenatide in the SUSTAIN trial program and a network meta-analysis (NMA). The aim of the present study was to assess the long-term cost-effectiveness of semaglutide versus all available GLP-1 receptor agonists in Denmark, using a clinically orientated treatment approach.

Methods

Outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline characteristics and treatment effects were sourced from the corresponding SUSTAIN trials and the NMA. Patients were assumed to initiate GLP-1 receptor agonist therapy and subsequently treatment-intensify according to clinical treatment guidelines, with addition of basal insulin and switching to basal-bolus insulin occurring when HbA1c exceeded recommended targets. Patients were assumed to receive a GLP-1 receptor agonist plus basal insulin therapy once HbA1c levels reached 7.5% and a basal-bolus insulin regimen once HbA1c exceeded 8.0%. Costs were captured in 2017 Danish kroner (DKK), with future costs and outcomes discounted at 3% per annum.

Results

Primary analyses indicated that semaglutide 0.5 mg and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.11 and 0.34 quality-adjusted life years, respectively, versus dulaglutide, achieved at cost savings of DKK 289 and DKK 13,416, respectively. Supporting analyses indicated that both doses of semaglutide were either cost-effective or dominant versus exenatide ER, liraglutide 1.2 mg and 1.8 mg and lixisenatide.

Conclusion

Semaglutide represents a cost-effective alternative to other GLP-1 receptor agonist therapies available in Denmark, demonstrating clinical benefits versus dulaglutide, exenatide ER, liraglutide and lixisenatide for the treatment of patients with T2D.

Funding

Novo Nordisk A/S. Plain language summary available for this article.

SUBMITTER: Gæde P

PROVIDER: S-EPMC6612343 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionOnce-weekly semaglutide 1 mg is a novel glucagon-like peptide 1 receptor agonist (GLP-1 RA) that, in the SUSTAIN clinical trials, has demonstrated greater reductions in glycated haemoglobin (HbA1c) and body weight than the other GLP-1 RAs exenatide extended-release (ER) 2 mg, dulaglutide 1.5 mg and liraglutide 1.2 mg. The aim of this analysis was to evaluate the relative cost of control of achieving treatment goals in people with type 2 diabetes (T2D) treated with once-weekly semaglutide versus exenatide ER, dulaglutide and liraglutide from a UK perspective.MethodsProportions of patients reaching HbA1c targets (< 7.0% and < 7.5%), weight loss targets (≥ 5% reduction in body weight) and composite endpoints (HbA1c < 7.0% without weight gain or hypoglycaemia; reduction in HbA1c of ≥ 1% and weight loss of ≥ 5%) were obtained from the SUSTAIN clinical trials. Annual per patient treatment costs were based on wholesale acquisition costs from July 2019 in the UK. Cost of control was calculated by plotting relative treatment costs against relative efficacy.ResultsThe annual per patient cost was similar for all GLP-1 RAs. Once-weekly semaglutide was superior to exenatide ER, dulaglutide and liraglutide in bringing patients to HbA1c and weight loss targets, and to composite endpoints. When looking at the composite endpoint of HbA1c < 7.0% without weight gain or hypoglycaemia, exenatide ER, dulaglutide and liraglutide were 50.0%, 21.6% and 51.3% less efficacious in achieving this, respectively, than once-weekly semaglutide. Consequently, the efficacy-to-cost ratios for once-weekly semaglutide were superior to all comparators in bringing patients to all endpoints.ConclusionsThe present study showed that once-weekly semaglutide offers superior cost of control versus exenatide ER, dulaglutide and liraglutide in terms of achieving clinically relevant, single and composite endpoints. Once-weekly semaglutide 1 mg would therefore represent good value for money in the UK setting.

Project description:AIMS:To evaluate adherence, persistence, glycaemic control and costs at 12-month follow-up for patients initiating dulaglutide versus liraglutide or exenatide once weekly. MATERIALS AND METHODS:The present retrospective observational claims study included patients with type 2 diabetes (T2D) and ≥ 1 pharmacy claim for dulaglutide, liraglutide or exenatide once weekly from the HealthCore Integrated Research Database. Adherence was defined as proportion of days covered ≥80%, and persistence was measured by time to discontinuation of index therapy. Change from baseline in glycated haemoglobin (HbA1c) concentration was assessed in a subset with pre- and post-index HbA1c results. Propensity scores were used to match the cohorts. RESULTS:The baseline characteristics were balanced for the matched cohorts, dulaglutide versus liraglutide (n = 2471) and dulaglutide versus exenatide once weekly (n = 1891). Among those initiating dulaglutide there was a significantly higher proportion of adherent patients compared with the groups initiating liraglutide (51.2% vs. 38.2%; P < 0.001) and exenatide once weekly (50.7% vs. 31.9%; P < 0.001). At 12 months, 55% of patients in the dulaglutide group versus 43.8% in the liraglutide group (P < 0.001), and 54.9% in the dulaglutide versus 34.4% in the exenatide once-weekly group (P < 0.001) were persistent. The dulaglutide group had a significantly greater reduction in HbA1c than the liraglutide group (-34.24 vs. -31.94 mmol/mol; P = 0.032), and a greater, but nonsignificant, reduction in HbA1c than the exenatide once-weekly group (-34.46 vs. -31.94 mmol/mol; P = 0.056). The diabetes-related total costs were not significantly different between the dulaglutide and the liraglutide group ($16,174 vs. $16,694; P = 0.184), and were significantly higher for dulaglutide than for exenatide once weekly ($15,768 vs. $14,615; P = 0.005). CONCLUSIONS:Adherence and persistence are important considerations in patient-centric treatment selection for patients with T2D. Higher adherence and persistence for dulaglutide compared with liraglutide or exenatide once weekly are relevant criteria when choosing glucagon-like peptide-1 receptor agonist treatment for patients with T2D.

Project description:ObjectiveIn SUSTAIN 7, once-weekly semaglutide demonstrated superior glycated haemoglobin (HbA1c) and body weight (BW) reductions versus once-weekly dulaglutide in subjects with type 2 diabetes (T2D). This post hoc analysis investigated the impact of clinically relevant subject characteristics on treatment effects of semaglutide versus dulaglutide.DesignAnalyses by baseline age (<65, ≥65 years), sex (male, female), diabetes duration (≤5, >5-10, >10 years), HbA1c (≤7.5, >7.5-8.5, >8.5% (≤58, >58-69, >69 mmol/mol)) and body mass index (BMI) (<30, 30-<35, ≥35 kg/m2).Setting194 sites; 16 countries.ParticipantsSubjects with T2D (n=1199) exposed to treatment.InterventionsSemaglutide 0.5 mg versus dulaglutide 0.75 mg (low-dose comparison); semaglutide 1.0 mg versus dulaglutide 1.5 mg (high-dose comparison), all subcutaneously once weekly.Primary and secondary outcome measuresChange in HbA1c (primary endpoint) and BW (confirmatory secondary endpoint) from baseline to week 40; proportion of subjects achieving HbA1c targets (<7%, ≤6.5% (<53, ≤48 mmol/mol)) and weight-loss responses (≥5%, ≥10%) at week 40; and safety.ResultsHbA1c and BW reductions (estimated treatment difference ranges: -0.22 to -0.70%-point; -1.76 to -3.84 kg) and proportion of subjects achieving HbA1c targets and weight-loss responses were statistically significantly greater for the majority of comparisons of semaglutide versus dulaglutide within each subgroup category and, excepting glycaemic control within the low-dose comparison in HbA1c subgroups, this was irrespective of subgroup or dose comparison. Gastrointestinal adverse events, the most common with both treatments, were reported by more women than men and, with semaglutide, decreased with increasing BMI.ConclusionsConsistently greater improvements in HbA1c and BW with semaglutide versus dulaglutide, regardless of age, sex, diabetes duration, glycaemic control and BMI, support the efficacy of semaglutide across the continuum of care in a heterogeneous population with T2D.Trial registration numberNCT02648204.

Project description:IntroductionOnce-weekly semaglutide 1 mg is a novel glucagon-like peptide-1 receptor agonist (GLP-1 RA) for the treatment of type 2 diabetes that has demonstrated significantly greater reductions in glycated haemoglobin (HbA1c) and body weight than the GLP-1 RA once-daily liraglutide 1.2 mg in the SUSTAIN 10 trial. The present analysis aimed to evaluate the long-term cost-effectiveness of once-weekly semaglutide 1 mg versus once-daily liraglutide 1.2 mg from a UK healthcare payer perspective.MethodsLong-term outcomes were projected using the IQVIA CORE Diabetes Model (version 9.0), with baseline characteristics and treatment effects sourced from SUSTAIN 10. Patients were assumed to initiate treatment with GLP-1 RAs and continue treatment until HbA1c exceeded 7.5%, at which point GLP-1 RAs were discontinued and basal insulin was initiated. Pharmacy costs and costs of complications were measured in 2018 pounds sterling (GBP), with future costs and outcomes discounted at 3.5% per annum. Utilities were taken from published sources.ResultsIn the base-case analysis, once-weekly semaglutide 1 mg was associated with an increase in discounted life expectancy of 0.21 years and discounted quality-adjusted life expectancy of 0.30 quality-adjusted life-years, compared with once-daily liraglutide 1.2 mg. Clinical benefits were achieved at reduced costs, with lifetime cost savings of GBP 140 per patient with semaglutide versus liraglutide, owing to a reduction in diabetes-related complications, in particular cardiovascular disease (mean cost saving of GBP 279 per patient). Therefore, once-weekly semaglutide 1 mg was dominant compared with once-daily liraglutide 1.2 mg. The results of the sensitivity analyses were similar, demonstrating the robustness of the base-case analysis.ConclusionsOnce-weekly semaglutide 1 mg is a cost-effective treatment option versus once-daily liraglutide 1.2 mg, based on the SUSTAIN 10 trial, from a UK healthcare payer perspective.

Project description:Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with substantial morbidity, mortality, and economic impacts. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as once-daily (QD) liraglutide and once-weekly (QW) exenatide, are FDA-approved treatment for T2DM. Head-to-head trials and meta-analyses comparing these agents have reported clinically meaningful improvements but small differences in glycemic control between both agents. In this study, we calculate and compare the cost-effectiveness implications of these alternative effectiveness outcomes.We developed a decision model to evaluate the short-term cost-effectiveness of exenatide QW 2 mg versus liraglutide QD 1.8 mg in T2DM patients, with effectiveness measured as reduction in glycated hemoglobin (HbA1c). In the base case, the model tracks change in HbA1c and direct medical expenditure over a 6-month time horizon. We calculated and compared the cost per 1% reduction in HbA1c of models populated with clinical data from a head-to-head randomized, controlled trial (DURATION-6) and a network meta-analysis. Expenditure inputs were derived from wholesale acquisition costs and published sources.In the base case, 6-month expenditure for the liraglutide and exenatide strategies were $3,509 and $2,618, respectively. Using clinical data from DURATION-6 and the network meta-analysis, the liraglutide strategy had an incremental cost per 1% reduction in HbA1c of $4,773 and $27,179, respectively. The most influential model parameters were drug costs, magnitude of HbA1c reduction in patients on treatment for >1 month, and liraglutide gastrointestinal adverse event rate. In probabilistic sensitivity analyses (PSA) using DURATION-6 data, the exenatide strategy was optimal at willingness-to-pay levels below $4,800 per 1% reduction in HbA1c. In a PSA using meta-analysis data, the exenatide strategy was dominant.Our modeled results demonstrate that the effectiveness and cost-effectiveness of liraglutide QD 1.8 mg relative to exenatide QW 2 mg depend largely on the chosen source of the clinical data.