Evaluating the Cost-Effectiveness of Once-Weekly Semaglutide 1 mg Versus Empagliflozin 25 mg for Treatment of Patients with Type 2 Diabetes in the UK Setting.

INTRODUCTION: Type 2 diabetes represents a continuing healthcare challenge, and choosing cost-effective treatments is crucial to ensure that healthcare resources are used efficiently. The present analysis assessed the cost-effectiveness of once-weekly semaglutide 1 mg versus empagliflozin 25 mg for the treatment of patients with type 2 diabetes mellitus with inadequate glycaemic control on metformin monotherapy from a healthcare payer perspective in the UK. METHODS: Outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Baseline cohort characteristics and treatment effects of initiation of once-weekly semaglutide 1 mg and empagliflozin 25 mg were based on an indirect comparison conducted using patient-level data, as there is currently no head-to-head clinical trial comparing these therapies. Modelled patients received treatments until glycated haemoglobin exceeded 7.5% (58 mmol/mol), at which point patients initiated basal insulin. The analysis captured pharmacy costs and costs of diabetes-related complications, expressed in 2019 pounds sterling (GBP). Projected outcomes were discounted at 3.5% annually. Scenario analyses were prepared to assess uncertainty around projected outcomes. RESULTS: Once-weekly semaglutide 1 mg was associated with increases in life expectancy and quality-adjusted life expectancy of 0.12 years and 0.23 quality-adjusted life years (QALYs), respectively, compared with empagliflozin 25 mg. Projected improvements in quality and duration of life resulted from a reduced cumulative incidence and a delayed time to onset of diabetes-related complications. Once-weekly semaglutide was associated with increased pharmacy costs, but this was partially offset by avoided costs of treating complications. Once-weekly semaglutide was associated with an increase in costs of GBP 1017 per patient, leading to an incremental cost-effectiveness ratio of GBP 4439 per QALY gained. CONCLUSION: Once-weekly semaglutide 1 mg was projected to be a cost-effective treatment option from a healthcare payer perspective compared with empagliflozin 25 mg for the treatment of patients with type 2 diabetes in the UK setting.

A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving Basal Insulin.

INTRODUCTION: Once-weekly semaglutide is a glucagon-like peptide-1 (GLP-1) analogue that is currently available as 1.0 mg and 0.5 mg dose for the treatment of type 2 diabetes (T2D). Currently, no head-to-head trial investigating once-weekly semaglutide as an add-on to basal insulin vs other GLP-1 receptor agonists (GLP-1 RAs) is available. The aim of this study was to conduct a network meta-analysis (NMA) to assess the efficacy and safety of once-weekly semaglutide vs other GLP-1 RAs in patients with T2D inadequately controlled on basal insulin. METHODS: A systematic literature review was performed to identify all trials of GLP-1 RAs as an add-on to basal insulin in patients with T2D. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in an NMA), including the change from baseline in glycated hemoglobin (HbA1c), body weight, and systolic blood pressure, and the incidence of nausea, vomiting, and diarrhea. Data were synthesized using a NMA and a Bayesian framework. RESULTS: In total, eight studies were included across the base-case analyses. The results demonstrate that once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c (- 0.88% to - 1.39% vs comparators) and weight (- 1.49 to - 4.69 kg vs comparators) and similar odds of experiencing nausea, vomiting, or diarrhea vs all GLP-1 RA comparators. Once-weekly semaglutide 1.0 mg was also equally effective at reducing systolic blood pressure compared with liraglutide 1.8 mg. Once-weekly semaglutide 0.5 mg significantly reduced HbA1c vs the majority of other GLP-1 RAs, except liraglutide 1.8 mg QD. The odds of experiencing nausea were significantly lower with once-weekly semaglutide 0.5 mg compared with all GLP-1 RA comparators. CONCLUSION: Once-weekly semaglutide 1.0 mg as an add-on to basal insulin is likely to be the most efficacious GLP-1 RA for reducing HbA1c and weight from baseline after 6 months of treatment. The efficacy of once-weekly semaglutide is not associated with a significant increase in the incidence of gastrointestinal side-effects vs other GLP-1 RAs. FUNDING: Novo Nordisk.

A Systematic Literature Review and Network Meta-Analysis Comparing Once-Weekly Semaglutide with Other GLP-1 Receptor Agonists in Patients with Type 2 Diabetes Previously Receiving 1-2 Oral Anti-Diabetic Drugs.

INTRODUCTION: Once-weekly semaglutide is a new glucagon-like peptide-1 (GLP-1) analogue administered at a 1.0 or 0.5 mg dose. As head-to-head trials assessing once-weekly semaglutide as an add-on to 1-2 oral anti-diabetic drugs (OADs) vs other GLP-1 receptor agonists (GLP-1 RAs) are limited, a network meta-analysis (NMA) was performed. The objective was to assess the relative efficacy and safety of once-weekly semaglutide vs GLP-1 RAs in patients with type 2 diabetes (T2D) inadequately controlled on 1-2 OADs. METHODS: A systematic literature review (SLR) was conducted in order to identify trials of GLP-1 RAs in patients inadequately controlled on 1-2 OADs. Data at 24 ± 4 weeks were extracted for efficacy and safety outcomes (feasible for analysis in a NMA), which included the key outcomes of change from baseline in glycated hemoglobin (HbA1c), systolic blood pressure (SBP), and weight, as well as discontinuation due to adverse events (AEs). Data were synthesized using a NMA and a Bayesian framework. RESULTS: In total, 26 studies were included across the base case analyses. Once-weekly semaglutide 1.0 mg was associated with significantly greater reductions in HbA1c and weight vs all GLP-1 RA comparators. Once-weekly semaglutide 0.5 mg also achieved significantly greater reductions in HbA1c and weight compared with the majority of other GLP-1 RAs. Both doses of once-weekly semaglutide were associated with similar odds of discontinuation due to AEs compared with other GLP-1 RAs. CONCLUSION: Overall, once-weekly semaglutide 1.0 mg as an add-on to 1-2 OADs is the most efficacious GLP-1 RA in terms of the reduction of HbA1c and weight from baseline after 6 months of treatment. In addition, the analysis suggests that once-weekly semaglutide is well tolerated and not associated with an increase in discontinuations due to AEs compared with other GLP-1 RAs. FUNDING: Novo Nordisk.

Cost-effectiveness of liraglutide versus lixisenatide as add-on therapies to basal insulin in type 2 diabetes.

BACKGROUND: We assessed the cost-effectiveness of the glucagon-like peptide 1 receptor agonists liraglutide 1.8 mg and lixisenatide 20 µg (both added to basal insulin) in patients with type 2 diabetes (T2D) in Sweden. METHODS: The Swedish Institute for Health Economics cohort model for T2D was used to compare liraglutide and lixisenatide (both added to basal insulin), with a societal perspective and with comparative treatment effects derived by indirect treatment comparison (ITC). Drug prices were 2016 values, and all other costs 2015 values. The cost-effectiveness of IDegLira (fixed-ratio combination of insulin degludec and liraglutide) versus lixisenatide plus basal insulin was also assessed, under different sets of assumptions. RESULTS: From the ITC, decreases in HbA1c were -1.32% and -0.43% with liraglutide and lixisenatide, respectively; decreases in BMI were -1.29 and -0.65 kg/m2, respectively. An estimated 2348 cases of retinopathy, 265 of neuropathy and 991 of nephropathy would be avoided with liraglutide compared with lixisenatide in a cohort of 10,000 patients aged over 40 years. In the base-case analysis, total direct costs were higher with liraglutide than lixisenatide, but costs associated with complications were lower. The cost/quality-adjusted life-year (QALY) for liraglutide added to basal insulin was SEK30,802. Base-case findings were robust in sensitivity analyses, except when glycated haemoglobin (HbA1c) differences for liraglutide added to basal insulin were abolished, suggesting these benefits were driving the cost/QALY. With liraglutide 1.2 mg instead of liraglutide 1.8 mg (adjusted for efficacy and cost), liraglutide added to basal insulin was dominant over lixisenatide 20µg.IDegLira was dominant versus lixisenatide plus basal insulin when a defined daily dose was used in the model. CONCLUSIONS: The costs/QALY for liraglutide, 1.8 or 1.2 mg, added to basal insulin, and for IDegLira (all compared with lixisenatide 20 µg added to basal insulin) were below the threshold considered low by Swedish authorities. In some scenarios, liraglutide and IDegLira were cost-saving.

Modeling the Long-Term Cost-Effectiveness of IDegLira in Patients with Type 2 Diabetes Who are Failing To Meet Glycemic Targets on Basal Insulin Alone in The Netherlands.

INTRODUCTION: Insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon-like peptide-1 receptor agonist (GLP-1 RA) in a single pen injection device, and a once-daily treatment option for patients with type 2 diabetes mellitus (T2DM) who are uncontrolled on basal insulin and require treatment intensification. The objective of this analysis was to evaluate the long-term cost-effectiveness of IDegLira versus basal-bolus therapy (insulin glargine U100 + 3× daily insulin aspart) for patients with T2DM uncontrolled on basal insulin [HbA1c >53 mmol/mol (>7%)] in the Netherlands. METHODS: Cost-effectiveness analysis was performed using the validated IMS CORE Diabetes Model from a healthcare payer perspective. Outcomes were modeled over patient lifetimes in a cohort with baseline characteristics from the DUAL™ II trial. Treatment effect data were sourced from a statistical indirect comparison (pooled analysis) of IDegLira with basal-bolus therapy. RESULTS: Treatment with IDegLira resulted in mean increases in quality-adjusted life expectancy of 0.43 quality-adjusted life years versus basal-bolus therapy. Improved clinical outcomes resulted from fewer diabetes-related complications and a delayed time to their onset. IDegLira was associated with lower costs of EUR 4679 versus basal-bolus therapy, a result of lower pharmacy costs and avoided diabetes-related complications. Thus, IDegLira was dominant, i.e., both more effective and less costly than basal-bolus therapy. CONCLUSIONS: IDegLira is an effective treatment option to improve glycemic control without incurring an increased risk of hypoglycemia or weight gain. This analysis suggests that IDegLira is cost-effective versus basal-bolus therapy in patients with T2DM who are uncontrolled on basal insulin in the Netherlands. FUNDING: Novo Nordisk.

Perceptions of general practitioners on initiation and intensification of type 2 diabetes injectable therapies. A quantitative study in the United Kingdom.

Most diabetes care is done by general practitioners (GPs) in the UK. This study aimed to determine GPs' comfort level in initiating and intensifying injectable therapies, identifying any associated barriers, and assessing reasons for referral to specialists. This web-interview included 128 general practitioners (GPs) experienced in type 2 diabetes (T2D) management, as well as 57 specialists and 30 nurses who were studied for secondary objectives. GPs felt more comfortable initiating the 1st injectable therapy - typically the glucagon-like peptide-1 receptor agonists (GLP-1 RA) - than the 2nd. The main barriers to initiating injectables were related to the complexity of injectable therapies and the lack of comfort with complex patient profiles, namely patients with difficultly achieving glycaemic control or those with significant comorbidities who GPs would rather refer to specialists. The main attributes that would increase their comfort level with initiation of injectables are improved glycaemic control, weight control and low risk of hypoglycaemia. An injectable therapy with these attributes could help to overcome barriers to initiating injectable therapies among GPs other healthcare professionals in primary care.

Cost Effectiveness of IDegLira vs. Alternative Basal Insulin Intensification Therapies in Patients with Type 2 Diabetes Mellitus Uncontrolled on Basal Insulin in a UK Setting.

OBJECTIVES: Once-daily insulin degludec/liraglutide (IDegLira) is the first basal insulin and glucagon like peptide-1 receptor agonist combined in one delivery device. Our aim was to investigate the cost effectiveness of IDegLira vs. basal insulin intensification therapies for patients with type 2 diabetes mellitus uncontrolled on basal insulin (glycosylated haemoglobin; HbA1c >7.5 %; 58 mmol/mol) in a UK setting. RESEARCH DESIGN AND METHODS: Baseline cohort and clinical parameters were sourced from a pooled analysis comparing IDegLira with basal insulin plus liraglutide and basal-bolus therapy, and from the DUAL™ V trial comparing IDegLira with up-titrated insulin glargine (IGlar; Lantus(®)). The CORE Diabetes Model simulated lifetime costs and outcomes with IDegLira vs. these comparators from a UK healthcare payers' perspective. All costs were expressed in 2015 GBP. Sensitivity analyses were performed to assess the impact of key parameters in the model. RESULTS: Treatment with IDegLira resulted in mean increases in quality-adjusted life-years (QALYs) of 0.12, 0.41 and 0.24 vs. basal insulin plus liraglutide, basal-bolus therapy and up-titrated IGlar, respectively. IDegLira was associated with lower costs of £971 and £1698 vs. basal insulin plus liraglutide and basal-bolus therapy, respectively, and increased costs of £1441 vs. up-titrated IGlar. IDegLira was dominant, i.e., both more effective and less costly vs. basal insulin plus liraglutide and basal-bolus therapy, and highly cost effective vs. up-titrated IGlar with an incremental cost-effectiveness ratio of £6090/QALY gained. CONCLUSIONS: Once-daily IDegLira may be considered a cost-effective treatment option for prescribers, to improve glycaemic control for type 2 diabetes patients uncontrolled on basal insulin without an increased risk of hypoglycaemia or weight gain, and without adding to their injection burden.

Resource use and outcomes associated with initiation of injectable therapies for patients with type 2 diabetes mellitus.

INTRODUCTION: Management of type 2 diabetes mellitus (T2DM) often requires intervention with oral and injectable therapies. Across National Health Service (NHS) England, injectable therapies may be initiated in secondary, intermediate or primary care. We wished to understand resource utilization, pathways of care, clinical outcomes, and experience of patients with T2DM initiated on injectable therapies. METHOD: We conducted three service evaluations of initiation of injectable therapies (glucagon-like peptide-1 receptor agonists (GLP-1 RAs) or basal insulin) for T2DM in primary, secondary and intermediate care. Evaluations included retrospective review of medical records and service administration; prospective evaluation of NHS staff time on each episode of patient contact during a 3-month initiation period; patient-experience survey for those attending for initiation. Data from each evaluation were analysed separately and results stratified by therapy type. RESULTS: A total of 133 patients were included across all settings; 54 were basal-insulin initiations. After initiation, the mean HbA1c level fell for both types of therapies, and weight increased for patients on basal insulin yet fell for patients on GLP-1 RA. The mean cost of staff time per patient per initiation was: £43.81 for GLP-1 RA in primary care; £243.49 for GLP-1 RA and £473.63 for basal insulin in intermediate care; £518.99 for GLP-1 RA and £571.11 for basal insulin in secondary care. Patient-reported questionnaires were completed by 20 patients, suggesting that patients found it easy to speak to the diabetes team, had opportunities to discuss concerns, and felt that these concerns were addressed adequately. CONCLUSION: All three services achieved a reduction in HbA1c level after initiation. Patterns of weight gain with basal insulin and weight loss with GLP-1 RA were as expected. Primary care was less resource-intensive and costly, and was driven by lower staff costs and fewer clinic visits.