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.

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.

New Therapeutic Horizons in Chronic Kidney Disease: The Role of SGLT2 Inhibitors in Clinical Practice.

Chronic kidney disease (CKD) is a serious, progressive condition associated with significant patient morbidity. Hypertension control and use of renin-angiotensin system blockers are the cornerstones of treatment for CKD. However, even with these treatment strategies, many individuals will progress towards kidney failure. Recently, sodium-glucose cotransporter 2 (SGLT2) inhibitor clinical trials with primary renal endpoints have firmly established SGLT2 inhibition, in addition to standard of care, as an effective strategy to slow down the progression of CKD and reduce some of its associated complications. The emergence of this new clinical evidence supports the use of SGLT2 inhibitors in the management of CKD in people with and without diabetes. As licensing and guidelines for SGLT2 inhibitors are updated, there is a need to adapt CKD treatment pathways and for this class of drugs to be included as part of standard care for CKD management. In this article, we have used consensus opinion alongside the available evidence to provide support for the healthcare community involved in CKD management, regarding the role of SGLT2 inhibitors in clinical practice. By highlighting appropriate prescribing and practical considerations, we aim to encourage greater and safe use of SGLT2 inhibitors for people with CKD, both with and without diabetes.

Optimising the Heart Failure Treatment Pathway: The Role of SGLT2 Inhibitors.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors were first developed as glucose-lowering therapies for the treatment of diabetes. However, these drugs have now been recognised to prevent worsening heart-failure events, improve health-related quality of life, and reduce mortality in people with heart failure with reduced ejection fraction (HFrEF), including those both with and without diabetes. Despite robust clinical trial data demonstrating favourable outcomes with SGLT2 inhibitors for patients with HFrEF, there is a lack of familiarity with the HF indication for these drugs, which have been the remit of diabetologists to date. In this article we use consensus expert opinion alongside the available evidence and label indication to provide support for the healthcare community treating people with HF regarding positioning of SGLT2 inhibitors within the treatment pathway. By highlighting appropriate prescribing and practical considerations, we hope to encourage greater, and safe, use of SGLT2 inhibitors in this population.

One Hundred Years of Insulin: Value Beyond Price in Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus is a chronic, progressive disease that frequently necessitates treatment with basal insulin to maintain adequate glycaemic control. In considering the value of different basal insulin therapies, although acquisition costs are of increasing importance to budget-constrained healthcare systems, value beyond simple price considerations should be taken into account. Whilst human basal insulins are of lower acquisition cost compared to long-acting insulin analogues, this difference in price has the potential to be offset in terms of total healthcare system value through the ultra-long duration of action and low variability in glucose-lowering activity which have been translated into real clinical benefits, in particular a reduced risk of hypoglycaemic events. The maintenance of glycaemic targets and avoidance of hypoglycaemia that have been associated with insulin analogues represent a significant value consideration, beyond price, for the use of basal insulin analogues to manage type 2 diabetes mellitus from the perspective of all stakeholders within the healthcare system, including payers, healthcare professionals, patients and society.

Costs of the COVID-19 pandemic associated with obesity in Europe: A health-care cost model.

Excess weight is associated with severe outcomes of coronavirus disease 2019 (COVID-19). We aimed to estimate the total secondary care costs by body mass index (BMI, kg/m2 ) category when hospitalized due to COVID-19 in Europe during the first wave of the pandemic from January to June 2020. Building a health-care cost model, this study aimed to estimate the total costs of COVID-19. Information on risk of hospitalization, admission to intensive care unit (ICU) and risk of ventilation were based on published data. Average cost per patient and in total were calculated based on risks of admission to ICU, risk of invasive mechanical ventilation and length of hospital stay when hospitalized and published costs associated with hospitalization. The total direct costs of secondary care during the first wave of COVID-19 in Europe were estimated at EUR 13.9 billon, whereof 76% accounted for treating people with overweight and obesity. The average cost per hospital admission increased with BMI, from EUR 15831 for BMI <25 kg/m2 to EUR 30982 for BMI ≥40 kg/m2 . This study reveals that excess weight contributes disproportionally to the costs of COVID-19. This might reflect that overweight and obesity caused the COVID-19 pandemic to result in more severe outcomes for citizens and higher secondary care costs throughout Europe.

Costs of COVID-19 pandemic associated with diabetes in Europe: a health care cost model.

OBJECTIVE: Diabetes is associated with progression to severe COVID-19. The objective of this study was to estimate to what extent the increased risk among people with diabetes could impact the secondary care costs of COVID-19 throughout Europe during the first wave of the COVID-19 pandemic from January to June 2020. METHODS: Applying a health care cost model based on inputs from data published in international peer-reviewed journals, identified via a rapid literature review this study aimed to estimate the total secondary sector costs of COVID-19. Estimates of unit costs were based on data from Denmark, France, Spain and the UK. We calculated average costs per patient without diabetes and according to four diabetes categories based on risk of hospitalization, admission to intensive care unit, ventilator support and length of hospital stay. RESULTS: The estimated cost per hospital admission during the first wave of COVID-19 in Europe ranged between EUR 25,018 among people with type 2 diabetes in good glycaemic control to EUR 57,244 among people with type 1 diabetes in poor glycaemic control, reflecting higher risk of intensive care, ventilator support and longer hospital stay according to diabetes category, while the corresponding cost for people without diabetes was estimated at EUR 16,993. The total direct costs of secondary care of COVID-19 in Europe were estimated at EUR 13.9 billion. Thus, 23.5% of the total costs accounted for treating people with diabetes. CONCLUSIONS: This study highlights the importance of a greater focus on prevention and adequate treatment of diabetes and the need for special attention to avoid infection with COVID-19 to the extent possible among those already diagnosed with diabetes.

Evaluating the burden of poor glycemic control associated with therapeutic inertia in patients with type 2 diabetes in the UK.

Background and aims: Effective glycemic control is the cornerstone of successful type 2 diabetes management. However, many patients fail to reach glycemic control targets, and therapeutic inertia (failure to intensify therapy to address poor glycemic control in a timely manner) has been widely reported. The aim of the present study was to evaluate the economic burden associated with diabetes-related complications due to poor glycemic control for patients with type 2 diabetes in the UK.Methods: A validated long-term model of type 2 diabetes (IQVIA CORE Diabetes Model) was used to project cost outcomes for a UK population with type 2 diabetes, based on data from The Health Improvement Network primary care database, at different levels of glycemic control. Costs associated with diabetes-related complications were accounted in 2017 Pounds Sterling (GBP). Complication costs were estimated for populations achieving different glycated hemoglobin (HbA1c) targets, in a number of delayed treatment intensification scenarios, and across a range of time horizons.Results: For patients with an HbA1c level of 8.2% (66 mmol/mol), 7 years in poor control could increase mean costs associated with diabetes-related complications by over GBP 690 per patient and lead to costs of over GBP 1,500 in lost workplace productivity compared with achieving good glycemic control (HbA1c 7.0%, 53 mmol/mol) over a 10-year time horizon. Based on published estimates of the proportion of type 2 diabetes patients failing to meet glycemic targets in the UK, this corresponds to an additional economic burden of ∼GBP 2,600 million (complication costs plus lost productivity costs).Conclusions: The economic burden of poor glycemic control in type 2 diabetes in the UK is substantial. Efforts to avoid therapeutic inertia could substantially reduce diabetes-related complication costs even in the short-term.

Oral Semaglutide Versus Empagliflozin, Sitagliptin and Liraglutide in the UK: Long-Term Cost-Effectiveness Analyses Based on the PIONEER Clinical Trial Programme.

INTRODUCTION: The PIONEER trial programme showed that, after 52 weeks, the novel oral glucagon-like peptide-1 (GLP-1) analogue semaglutide 14 mg was associated with significantly greater reductions in glycated haemoglobin (HbA1c) versus a sodium-glucose cotransporter-2 inhibitor (empagliflozin 25 mg), a dipeptidyl peptidase-4 inhibitor (sitagliptin 100 mg) and an injectable GLP-1 analogue (liraglutide 1.8 mg). The aim of the present analysis was to assess the long-term cost-effectiveness of oral semaglutide 14 mg versus each of these comparators in the UK setting. METHODS: Analyses were performed from a healthcare payer perspective using the IQVIA CORE Diabetes Model, in which outcomes were projected over patient lifetimes (50 years). Baseline cohort characteristics and treatment effects were based on 52-week data from the PIONEER 2, 3 and 4 randomised controlled trials, comparing oral semaglutide with empagliflozin, sitagliptin and liraglutide, respectively. Treatment switching occurred when HbA1c exceeded 7.5% (58 mmol/mol). Utilities, treatment costs and costs of diabetes-related complications (in pounds sterling [GBP]) were taken from published sources. The acquisition cost of oral semaglutide was assumed to match that of once-weekly semaglutide. RESULTS: Oral semaglutide was associated with improvements in quality-adjusted life expectancy of 0.09 quality-adjusted life years (QALYs) versus empagliflozin, 0.20 QALYs versus sitagliptin and 0.07 QALYs versus liraglutide. Direct costs over a patient's lifetime were GBP 971 and GBP 963 higher with oral semaglutide than with empagliflozin and sitagliptin, respectively, but GBP 1551 lower versus liraglutide. Oral semaglutide was associated with a reduced incidence of diabetes-related complications versus all comparators. Therefore, oral semaglutide 14 mg was associated with incremental cost-effectiveness ratios of GBP 11,006 and 4930 per QALY gained versus empagliflozin 25 mg and sitagliptin 100 mg, respectively, and was more effective and less costly (dominant) versus liraglutide 1.8 mg. CONCLUSION: Oral semaglutide was cost-effective versus empagliflozin and sitagliptin, and dominant versus liraglutide, for the treatment of type 2 diabetes in the UK.

Evaluation of the long-term cost-effectiveness of once-weekly semaglutide versus dulaglutide for treatment of type 2 diabetes mellitus in the UK.

AIMS: Glucagon-like peptide-1 (GLP-1) receptor agonists are appealing as glucose-lowering therapy for individuals with type 2 diabetes mellitus (T2DM) as they also reduce body weight and are associated with low rates of hypoglycaemia. This analysis assessed the long-term cost-effectiveness of semaglutide 0.5 and 1 mg vs dulaglutide 1.5 mg (two once-weekly GLP-1 receptor agonists) from a UK healthcare payer perspective, based on the head-to-head SUSTAIN 7 trial, to inform healthcare decision making. MATERIALS AND METHODS: Long-term outcomes were projected using the IQVIA CORE Diabetes Model (version 9.0). Baseline cohort characteristics, changes in physiological parameters and adverse event rates were derived from the 40-week SUSTAIN 7 trial. Costs to a healthcare payer were assessed, and these captured pharmacy costs and costs of complications. Utilities were taken from published sources. RESULTS: Once-weekly semaglutide 0.5 and 1 mg were associated with improvements in quality-adjusted life expectancy of 0.04 and 0.10 quality-adjusted life years, respectively, compared with dulaglutide 1.5 mg. Clinical benefits were achieved at reduced costs, with lifetime cost savings of GBP 35 with once-weekly semaglutide 0.5 mg and GBP 106 with the once-weekly semaglutide 1 mg, resulting from fewer diabetes-related complications due to better glycaemic control. Therefore, both doses of once-weekly semaglutide were considered dominant vs dulaglutide 1.5 mg (improving outcomes and reducing costs). CONCLUSIONS: Compared with treatment with dulaglutide, once-weekly semaglutide represents a cost-effective option for treating individuals in the UK with T2DM who are not achieving glycaemic control with metformin, projected to both improve clinical outcomes and reduce costs.

Poor glycaemic control is associated with reduced exercise performance and oxygen economy during cardio-pulmonary exercise testing in people with type 1 diabetes.

BACKGROUND: To explore the impact of glycaemic control (HbA1c) on functional capacity during cardio-pulmonary exercise testing in people with type 1 diabetes. METHODS: Sixty-four individuals with type 1 diabetes (age: 34 ± 8 years; 13 females, HbA1c: 7.8 ± 1% (62 ± 13 mmol/mol), duration of diabetes: 17 ± 9 years) performed a cardio-pulmonary cycle ergometer exercise test until volitional exhaustion. Stepwise linear regression was used to explore relationships between HbA1c and cardio-respiratory data with p ≤ 0.05. Furthermore, participants were divided into quartiles based on HbA1c levels and cardio-respiratory data were analysed by one-way ANOVA. Multiple regression analysis was performed to explore the relationships between changes in time to exhaustion and cardio-respiratory data. Data were adjusted for confounder. RESULTS: HbA1c was related to time to exhaustion and oxygen consumption at the power output elicited at the sub-maximal threshold of the heart rate turn point (r = 0.47, R2 = 0.22, p = 0.03). Significant differences were found at time to exhaustion between QI vs. QIV and at oxygen consumption at the power output elicited at the heart rate turn point between QI vs. QII and QI vs. QIV (p < 0.05). Changes in oxygen uptake, power output and in oxygen consumption at the power output elicited at the heart rate turn point and at maximum power output explained 55% of the variance in time to exhaustion (r = 0.74, R2 = 0.55, p < 0.01). CONCLUSIONS: Poor glycaemic control is related to less economical use of oxygen at sub-maximal work rates and an earlier time to exhaustion during cardio-pulmonary exercise testing. However, exercise training could have the same potential to counteract the influence of poor glycaemic control on functional capacity. Trial registration NCT01704417. Date of registration: October 11, 2012.

Cost-effective strategies in the prevention of diabetic nephropathy.

A significant subgroup of patients with diabetes mellitus are predisposed to developing diabetic nephropathy and it is in this subgroup that other diabetes- related complications, and in particular greatly increased cardiovascular disease risk, are concentrated. The high personal, social and financial costs of managing end-stage renal failure and the other complications associated with diabetic nephropathy make a powerful case for screening and effective intervention programmes to prevent the condition or retard its progression. As major breakthroughs in finding genetic susceptibility factors remain elusive, screening efforts continue to be based on microalbuminuria testing, despite increasing recognition of its limitations as a positive predictor of nephropathy. Interventions have been extensively studied, but results remain conflicting. Economic evaluations of such screening and intervention programmes are essential for health planners, yet models of the cost/benefit ratio of such interventions often rely on a rather slim evidence base. Where economic models are developed, they are frequently based on those papers that propound the greatest clinical benefits of a given intervention, leading to a possible over-estimation of the advantages of the chosen approach. Furthermore, the benefits of even such generally accepted interventions as ACE inhibitor treatment are less firmly established than generally appreciated. Lifestyle interventions are instinctively attractive, but are by no means a low-cost option (as is often assumed by both medical professionals and politicians). This review critically assesses the evidence for clinical efficacy and economic benefit of microalbuminuria screening and interventions such as intensive glycaemic control, antihypertensive treatment, ACE inhibition and angiotensin receptor blockade, dietary protein restriction and lipid-modifying therapy. The various costs associated with diabetic nephropathy are so great that even expensive interventions may have a favourable cost/benefit ratio, provided they are truly effective.