Associations of clinical, psychological, and sociodemographic characteristics and ecological momentary assessment completion in the 10-week Hypo-METRICS study: Hypoglycaemia MEasurements ThResholds and ImpaCtS.

INTRODUCTION: Reporting of hypoglycaemia and its impact in clinical studies is often retrospective and subject to recall bias. We developed the Hypo-METRICS app to measure the daily physical, psychological, and social impact of hypoglycaemia in adults with type 1 and insulin-treated type 2 diabetes in real-time using ecological momentary assessment (EMA). To help assess its utility, we aimed to determine Hypo-METRICS app completion rates and factors associated with completion. METHODS: Adults with diabetes recruited into the Hypo-METRICS study were given validated patient-reported outcome measures (PROMs) at baseline. Over 10 weeks, they wore a blinded continuous glucose monitor (CGM), and were asked to complete three daily EMAs about hypoglycaemia and aspects of daily functioning, and two weekly sleep and productivity PROMs on the bespoke Hypo-METRICS app. We conducted linear regression to determine factors associated with app engagement, assessed by EMA and PROM completion rates and CGM metrics. RESULTS: In 602 participants (55% men; 54% type 2 diabetes; median(IQR) age 56 (45-66) years; diabetes duration 19 (11-27) years; HbA1c 57 (51-65) mmol/mol), median(IQR) overall app completion rate was 91 (84-96)%, ranging from 90 (81-96)%, 89 (80-94)% and 94(87-97)% for morning, afternoon and evening check-ins, respectively. Older age, routine CGM use, greater time below 3.0 mmol/L, and active sensor time were positively associated with app completion. DISCUSSION: High app completion across all app domains and participant characteristics indicates the Hypo-METRICS app is an acceptable research tool for collecting detailed data on hypoglycaemia frequency and impact in real-time.

Producing a preference-based quality of LIFE measure to quantify the impact of HYPOGLYCAEMIA on people living with diabetes: A mixed-methods research protocol.

BACKGROUND: Assessment of patient-reported outcome measures (PROMs), including quality of life (QoL), is essential in diabetes research and care. However, a recent review concluded that current hypoglycaemia-specific PROMs have limited evidence of validity, reliability and responsiveness for assessing the impact of hypoglycaemia on QoL in people living with diabetes. None of the PROMs identified could be used directly to inform the cost-effectiveness of treatments and interventions. There is a need for a new hypoglycaemia-specific QoL PROM, which can be used directly to inform economic evaluations. AIMS: This project has three aims: (a) To develop draft PROM content for measuring the impact of hypoglycaemia on QoL in adults with diabetes. (b) To refine the draft content using cognitive debriefing interviews and psychometrics. This will result in a condition-specific PROM that can be used to quantify the impact of hypoglycaemia upon QoL. (c) To generate a preference-based measure (PBM) that will enable utility values to be calculated for economic evaluation. METHODS: A mixed-methods, three-stage design is used: (a) Qualitative interviews will inform the draft PROM content. (b) Cognitive debriefing interview data will be used to refine the draft PROM content. The PROM will be administered in a large-scale survey to enable psychometric validation. Final item selection for the PROM will be informed by psychometric performance, translatability assessment and input from stakeholder groups. (c) A classification system will be generated, comprising a reduced number of items from the PROM. A valuation survey will be conducted to derive a value set for the PBM.

Hypo-METRICS: Hypoglycaemia-MEasurement, ThResholds and ImpaCtS-A multi-country clinical study to define the optimal threshold and duration of sensor-detected hypoglycaemia that impact the experience of hypoglycaemia, quality of life and health economic outcomes: The study protocol.

INTRODUCTION: Hypoglycaemia is a significant burden to people living with diabetes and an impediment to achieving optimal glycaemic outcomes. The use of continuous glucose monitoring (CGM) has improved the capacity to assess duration and level of hypoglycaemia. The personal impact of sensor-detected hypoglycaemia (SDH) is unclear. Hypo-METRICS is an observational study designed to define the threshold and duration of sensor glucose that provides the optimal sensitivity and specificity for events that people living with diabetes experience as hypoglycaemia. METHODS: We will recruit 600 participants: 350 with insulin-treated type 2 diabetes, 200 with type 1 diabetes and awareness of hypoglycaemia and 50 with type 1 diabetes and impaired awareness of hypoglycaemia who have recent experience of hypoglycaemia. Participants will wear a blinded CGM device and an actigraphy monitor to differentiate awake and sleep times for 10 weeks. Participants will be asked to complete three short surveys each day using a bespoke mobile phone app, a technique known as ecological momentary assessment. Participants will also record all episodes of self-detected hypoglycaemia on the mobile app. We will use particle Markov chain Monte Carlo optimization to identify the optimal threshold and duration of SDH that have optimum sensitivity and specificity for detecting patient-reported hypoglycaemia. Key secondary objectives include measuring the impact of symptomatic and asymptomatic SDH on daily functioning and health economic outcomes. ETHICS AND DISSEMINATION: The protocol was approved by local ethical boards in all participating centres. Study results will be shared with participants, in peer-reviewed journal publications and conference presentations.

Cost-Effectiveness of iGlarLixi Versus Premix BIAsp 30 in Patients with Type 2 Diabetes Suboptimally Controlled by Basal Insulin in the UK.

INTRODUCTION: iGlarLixi is indicated as an adjunct to diet and exercise in addition to metformin (with or without sodium-glucose cotransporter-2 inhibitors) to improve glycemic control in adults with insufficiently controlled type 2 diabetes (T2D). A cost-effectiveness analysis was conducted to compare iGlarLixi with premix biphasic insulin aspart 30 (BIAsp 30) in people with T2D suboptimally controlled with basal insulin (BI). METHODS: The IQVIA CORE Diabetes Model was used to estimate lifetime costs and outcomes for people with T2D from a UK health care perspective at a willingness-to-pay threshold of £20,000. Initial clinical data were based on the phase 3 randomized, open-label, active-controlled SoliMix clinical trial which compared the efficacy and safety of once-daily iGlarLixi with that of twice-daily BIAsp 30. Costs associated with management and complications and utilities values were derived from published sources. Lifetime costs (in £GBP) and quality-adjusted life-years (QALYs) were predicted; extensive scenario and sensitivity analyses were conducted. RESULTS: Estimated QALYs gained were slightly higher with iGlarLixi (8.9 vs. 8.8) compared with premix BIAsp 30, at a higher cost (£23,204 vs. £21,961). The base case incremental cost-effectiveness ratio (ICER) per QALY was £13,598. Treatment acquisition was the main driver of cost differences (iGlarLixi, £11,750; premix BIAsp 30, £10,395). Costs associated with management and complications were generally similar between comparators. CONCLUSION: iGlarLixi provides improved QALY outcomes at an acceptable cost compared with premix BIAsp 30, with an ICER below the threshold generally considered acceptable by UK authorities. In people with T2D, iGlarLixi is a simple, cost-effective option for advancing therapy of BI, with fewer daily injections than premix BIAsp 30.

Cost-Effectiveness of iGlarLixi in People with Type 2 Diabetes Mellitus Suboptimally Controlled on Basal Insulin Plus Metformin in the UK.

INTRODUCTION: A cost-effectiveness analysis was conducted comparing a fixed-ratio combination (FRC) of insulin glargine 100 units/mL plus lixisenatide (iGlarLixi) versus the FRC of insulin degludec plus liraglutide (iDegLira) and the free-combination comparators insulin glargine plus dulaglutide (iGlar plus Dula) and basal insulin plus liraglutide (BI plus Lira). METHODS: The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes for a cohort of patients with type 2 diabetes mellitus (T2DM) from the UK healthcare perspective. Initial clinical data for iGlarLixi were based on the randomized, controlled LixiLan-L trial and the relative treatment effects for comparators were based on an indirect treatment comparison using data from the AWARD-9 (iGlar plus Dula), LIRA ADD2 BASAL (BI plus Lira), and DUAL V (iDegLira) trials. Costs were derived from publicly available sources. Lifetime costs (in British Pound Sterling [£]) and quality-adjusted life-years (QALYs) were predicted; net monetary benefit (NMB) for iGlarLixi versus comparators was derived using a willingness-to-pay threshold of £20,000. Extensive scenario and sensitivity analyses were conducted. RESULTS: Estimated costs were lowest with iGlarLixi (£31,295) compared with iGlar plus Dula (£38,790), iDegLira (£40,179), and BI plus Lira (£42,467). Total QALYs gained were identical with iGlarLixi and iDegLira (8.438), and comparable with iGlar plus Dula (8.439) and BI plus Lira (8.466). NMB for iGlarLixi was positive versus all comparators (£10,603.86 vs. BI plus Lira; £7,466.24 vs. iGlar plus Dula; £8.874.11 vs. iDegLira). CONCLUSION: In patients with T2DM with suboptimal glycemic control on basal insulin, iGlarLixi provides very similar outcomes and substantial cost savings, compared with other fixed and free combinations of insulins plus glucagon-like peptide-1 receptor agonists.

Cost-Effectiveness of iGlarLixi Versus iDegLira in Type 2 Diabetes Mellitus Inadequately Controlled by GLP-1 Receptor Agonists and Oral Antihyperglycemic Therapy.

INTRODUCTION: The fixed-ratio combinations (FRCs) of glucagon-like peptide 1 receptor agonists (GLP-1 RAs) and basal insulin, insulin glargine 100 U/mL plus lixisenatide (iGlarLixi), and insulin degludec plus liraglutide (iDegLira), have demonstrated safety and efficacy in patients with type 2 diabetes mellitus (T2DM) inadequately controlled on GLP-1 RAs. However, a comparative cost-effectiveness analysis between these FRCs from a UK Health Service perspective has not been conducted. METHODS: The IQVIA Core Diabetes Model was used to estimate lifetime costs and outcomes in patients with T2DM receiving iGlarLixi (based on the LixiLan-G trial) versus iDegLira (based on relative treatment effects from an indirect treatment comparison using data from DUAL III). Utilities, medical costs, and costs of diabetes-related complications were derived from literature. Model outputs included costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios were calculated with a local willingness-to-pay threshold of £20,000 per QALY. Extensive scenario, one-way sensitivity, and probabilistic sensitivity analyses were conducted to evaluate the robustness of the model. RESULTS: iGlarLixi was less costly (iGlarLixi, £30,011; iDegLira, £40,742), owing to lower acquisition costs, and similar in terms of QALYs gained (iGlarLixi, 8.437; iDegLira, 8.422). Extensive scenario and sensitivity analyses supported the base case findings. CONCLUSION: In patients with T2DM and inadequate glycemic control despite GLP-1 RAs, use of iGlarLixi was associated with substantial cost savings and comparable utility outcomes. iGlarLixi can be considered as cost-effective versus iDegLira from the UK Health Service perspective.