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Objective: To estimate using the UK Prospective Diabetes Study Outcomes Model Version 2 (UKPDS-OM2) the impact of delaying type 2 diabetes onset on costs and quality-adjusted life expectancy using trial participants who developed diabetes in the NAVIGATOR (Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research) study.Research Design and Methods: We simulated the impact of delaying diabetes onset by 1-9 years, utilizing data from the 3,058 of 9,306 NAVIGATOR trial participants who developed type 2 diabetes. Costs and utility weights associated with diabetes and diabetes-related complications were obtained for the U.S. and U.K. settings, with costs expressed in 2017 values. We estimated discounted lifetime costs and quality-adjusted life years (QALYs) with 95% CIs.Results: Gains in QALYs increased from 0.02 (U.S. setting, 95% CI 0.01, 0.03) to 0.15 (U.S. setting, 95% CI 0.10, 0.21) as the imposed time to diabetes onset was increased from 1 to 9 years, respectively. Savings in complication costs increased from $1,388 (95% CI $1,092, $1,669) for a 1-year delay to $8,437 (95% CI $6,611, $10,197) for a delay of 9 years. Interventions costing up to $567-$2,680 and £201-£947 per year would be cost-effective at $100,000 per QALY and £20,000 per QALY thresholds in the U.S. and U.K., respectively, as the modeled delay in diabetes onset was increased from 1 to 9 years.Conclusions: Simulating a hypothetical diabetes-delaying intervention provides guidance concerning the maximum cost and minimum delay in diabetes onset needed to be cost-effective. These results can inform the ongoing debate about diabetes prevention strategies and the design of future intervention studies. [ABSTRACT FROM AUTHOR]

Aim: To perform post‐hoc analyses of the EMPA‐REG OUTCOME trial examining the degree to which empagliflozin‐induced changes in conventional cardiovascular (CV) risk factors might explain the observed CV benefits. Materials and methods: We estimated 3‐year EMPA‐REG OUTCOME CV event rates using a type 2 diabetes‐specific clinical outcomes simulation model applied to annual patient‐level data. Variables included were atrial fibrillation, smoking, albuminuria, HDL cholesterol, LDL cholesterol, systolic blood pressure, glycated haemoglobin, heart rate, white cell count, haemoglobin, estimated glomerular filtration rate, and histories of ischaemic heart disease, heart failure, amputation, blindness, renal failure, stroke, myocardial infarction or diabetic ulcer. Multiple simulations were performed for each participant to minimize uncertainty and optimize confidence interval precision around CV risk point estimates. Observed and simulated cardiovascular relative risk reductions were compared. Results: Model‐predicted relative risk reductions were smaller than those observed in the trial, with empagliflozin‐associated changes in conventional CV risk factor values appearing to explain only 12% of the observed relative risk reduction for all‐cause death (4% of 32%), 7% for CV death (3% of 39%) and 15% for heart failure (4% of 29%). Conclusions: Empagliflozin‐associated changes in conventional CV risk factors in EMPA‐REG OUTCOME appear to explain only a small proportion of the CV and all‐cause death reductions observed. Alternative risk‐reduction mechanisms need to be explored to determine if the observed CV risk changes can be explained by other factors, or possibly by a direct drug‐specific effect. [ABSTRACT FROM AUTHOR]

Objective: To compare medical resource use, costs, and health utilities for 14,752 patients with type 2 diabetes who were randomized to once-weekly exenatide (EQW) or placebo in addition to usual diabetes care in the Exenatide Study of Cardiovascular Event Lowering (EXSCEL).Research Design and Methods: Medical resource use data and responses to the EuroQol 5-Dimension (EQ-5D) instrument were collected at baseline and throughout the trial. Medical resources and medications were assigned values by using U.S. Medicare payments and wholesale acquisition costs, respectively. Secondary analyses used English costs.Results: Patients were followed for an average of 3.3 years, during which time those randomized to EQW experienced 0.41 fewer inpatient days (7.05 vs. 7.46 days; relative rate ratio 0.91; P = 0.05). Rates of outpatient medical visits were similar, as were total inpatient and outpatient costs. Mean costs for nonstudy diabetes medications over the study period were ∼$1,600 lower with EQW than with placebo (P = 0.01). Total within-study costs, excluding study medication, were lower in the EQW arm than in the placebo arm ($28,907 vs. $30,914; P ≤ 0.01). When including the estimated cost of EQW, total mean costs were significantly higher in the EQW group than in the placebo group ($42,697 vs. $30,914; P < 0.01). With English costs applied, mean total costs, including exenatide costs, were £1,670 higher in the EQW group than the placebo group (£10,874 vs. £9,204; P < 0.01). There were no significant differences in EQ-5D health utilities between arms over time.Conclusions: Medical costs were lower in the EQW arm than the placebo arm, but total costs were significantly higher once the cost of branded exenatide was incorporated. [ABSTRACT FROM AUTHOR]

Objectives: We applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.Methods: The Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.Results: We observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.Conclusions: Atorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. [ABSTRACT FROM AUTHOR]

Annuity is a purchased policy that pays a fixed yearly benefit during the life of a person. There is no final lump sum payment and no provision to pay benefits to a spouse or other survivor. Insurance companies often offer people with diabetes "enhanced impaired life annuity" at preferential rates, in view of their reduced life-expectancy. To assess the appropriateness of these rates, we estimated individual life-expectancy for 4005 subjects with established type 2 diabetes (but not known cardiovascular or other life threatening diseases) enrolled into the UK Lipids in Diabetes Study, using the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model. Subjects were mean (SD) age 60.7 (8.6) years, systolic blood pressure 141 (17) mmHg, total cholesterol 4.5 (0.75) mM, HDL cholesterol 1.2 (0.29) mM with median (IQR) diabetes-duration 6 (3-11) years and HbA[sub 1c] 8.0 (7.2-9.0) %. 65% were male, 91% white Caucasian, 4% Afro-Caribbean, 5% Indian-Asian. 15% were current smokers. Mean (SD) estimated age at death was 76.6 (3.8) years compared with 81.4 (2.3) years estimated using UK Government Actuary's Department data for a general population of the same age and gender structure. The mean difference was 4.74 (95%CI 4.66 to 4.83) years, a life-expectancy reduction of almost one quarter. The highest value annuity we identified that commences payments at age 65 years for a 60 year old man with insulin-treated type 2 diabetes investing $200,000 did not reflect this difference, offering $14.3k/year compared with $12.7k/year if not diabetic. Conclusion: The UK Government Actuary's Department data overestimate likely age at death in type 2 diabetes. Using a diabetes-specific model to estimate life expectancy could provide valuable information to the annuity industry and permit more equitable annuity rates for those with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: There are few data available on the incremental benefits of risk factor modification in type 2 diabetes mellitus (T2DM). We simulated the potential benefits of achieving lower systolic blood pressure (SBP) and LDL-cholesterol targets.Methods: We used the UKPDS Outcomes Model v2.0 to estimate 10-year event rates for complications using baseline data from 5717 participants with T2DM in the Trial Evaluating Cardiovascular Outcomes with Sitagliptin Study. All risk factor values were held constant over 10 years. In separate analyses, different levels of SBP between 160 and 120 mm Hg and LDL-cholesterol between 5.0 and 1.0 mmol/l were imposed on the cohort. Cumulative relative risk reductions (CRRR) at each 10 mm Hg and 1.0 mmol/l decrements respectively were compared using Kruskal-Wallis tests.Results: CRRRs for each 10 mm Hg SBP decrement from 160 mm Hg were 2.2%, 4.5%, 7.0% and 10.0% for myocardial infarction (MI); 12.5%, 24.8%, 35.6% and 44.9% for stroke; 5.4%, 10.9%, 16.2% and 20.9% for blindness; 7.4%, 14.7%, 21.6% and 27.4% for amputation, respectively. CRRRs for each 1.0 mmol/l LDL-cholesterol decrement from 5.0 mmol/l were 16.9%, 30.8%, 41.2% & 51.0% for MI; 9.2%, 19.7%, 29.6% & 38.8% for stroke (p < 0.001 in all cases).Conclusions: These simulated outcomes illustrate the potential benefits of targeting progressively lower SBP and LDL-cholesterol values. [ABSTRACT FROM AUTHOR]

Aims: The Exenatide Study of Cardiovascular Event Lowering (EXSCEL) trial assessed once-weekly exenatide (EQW) vs. placebo, added to usual care in 14,752 patients with type 2 diabetes mellitus (Clinicaltrials.gov: NCT01144338). We assessed the lifetime cost-effectiveness of adding EQW vs. usual care alone from a healthcare perspective.Methods: Medical resource use and EQ-5D utilities were collected throughout the study. Within-trial results were extrapolated to a lifetime horizon using the UK Prospective Diabetes Study Outcomes Model version 2 (UKPDS-OM2), predicting predict cardiovascular and microvascular events. Cost-effectiveness was evaluated separately for US and UK settings, with outcomes measured in quality-adjusted life-years (QALYs).Results: EQW plus usual care gained 0.162 QALYs at an additional cost of $41,545/patient, compared with usual care in a US setting. The incremental cost-effectiveness ratio (ICER) was $259,223/QALY. In a UK setting, the QALY gain was 0.151 at an additional cost of £6357: an ICER of £42,589/QALY. Sensitivity analyses ranged between $34,369-$269,571 and £3430-£46,560 per QALY gained.Conclusions: In a lifetime extrapolation, adding EQW to usual care increased QALYs and costs compared with usual care alone. The base-case ICERs exceeded the commonly-cited cost-effectiveness thresholds of $100,000/QALY and £20,000/QALY. However, ICERs were considerably lower in some subgroups, and in sensitivity analyses. [ABSTRACT FROM AUTHOR]