Factors Predictive of Weight Gain and Implications for Modeling in Type 2 Diabetes Patients Initiating Metformin and Sulfonylurea Combination Therapy.

INTRODUCTION: The objectives of this study were to (a) assess the factors associated with weight gain in a population of type 2 diabetes patients escalating from metformin (M) to M+ sulfonylurea (M + S) and (b) evaluate whether healthcare resource utilization associated with being overweight or obese is underestimated in typical health economic evaluations. METHODS: The study was a retrospective cohort study using UK Clinical Practice Research Datalink linked to Hospital Episode Statistics (CPRD/HES) data. The association between baseline phenotypic factors and weight gain was assessed using logistic regression. Hospitalization incidence rates per 1000 person-years for major diabetes-related complications according to body mass index (BMI) at baseline were estimated from the data (observed) and compared to those obtained from a validated diabetes model (predicted). RESULTS: 11,071 patients were included in the analysis; approximately 40% gained weight in the first year following escalation to M + S. Baseline age, HbA1c and gender were found to be predictors of weight gain [odds ratios 0.99 (1-year increment), 1.11 (1% increment) and 0.81 (female vs male), respectively, p < 0.001]. Observed vs predicted incidence rates of hospitalization were 265 vs 13 (normal), 297 vs 31 (overweight), 223 vs 50 (obese) and 378 vs 41 (severe obese). CONCLUSION: This analysis suggests there are identifiable patient characteristics predictive of weight gain that may be informative to clinical and economic decision making in the context of patients escalating from M to an M + S regimen. Hospital admissions in people with type 2 diabetes were generally under-predicted. A particular focus of future research should be the need for diabetes models to make the likelihood of experiencing an event conditional on BMI. FUNDING: Takeda Development Centre Europe Ltd., UK.

Validation of the UKPDS 82 risk equations within the Cardiff Diabetes Model.

BACKGROUND: For end-users of diabetes models that include UKPDS 82 risk equations, an important question is how well these new equations perform. Consequently, the principal objective of this study was to validate the UKPDS 82 risk equations, embedded within an established type 2 diabetes mellitus (T2DM) model, the Cardiff Diabetes Model, to contemporary T2DM outcomes studies. METHODS: A total of 100 validation endpoints were simulated across treatment arms of twelve pivotal T2DM outcomes studies, simulation cohorts representing each validation study's cohort profile were generated and intensive and conventional treatment arms were defined in the Cardiff Diabetes Model. RESULTS: Overall the validation coefficient of determination was similar between both sets of risk equations: UKPDS 68, R(2) = 0.851; UKPDS 82, R(2) = 0.870. Results stratified by internal and external validation studies produced MAPE of 43.77 and 37.82%, respectively, when using UKPDS 82, and MAPE of 40.49 and 53.92%, respectively when using UKPDS 68. Areas of lack of fit, as measured by MAPE were inconsistent between sets of equations with ACCORD demonstrating a noteworthy lack of fit with UKPPDS 68 (MAPE = 170.88%) and the ADDITION study for UKPDS 82 (MAPE = 89.90%). CONCLUSIONS: This study has demonstrated that the UKPDS 82 equations exhibit similar levels of external validity to the UKPDS 68 equations with the additional benefit of enabling more diabetes related endpoints to be modeled.

Healthcare resource implications of hypoglycemia-related hospital admissions and inpatient hypoglycemia: retrospective record-linked cohort studies in England.

OBJECTIVE: Using a retrospective cohort study, the mean length of hospital stay (LoS) and total per-patient expenditure for hypoglycemia requiring admission to hospital were estimated. In a separate matched retrospective cohort study, the effect of inpatient hypoglycemia on LoS, expenditure, and risk of all-cause mortality while admitted was investigated. METHODS: The cohorts consisted of patients aged ≥18 years with a diagnosis of type 1 or 2 diabetes between January 1, 2002 and October 30, 2012 in the Clinical Practice Research Datalink database, who had initiated insulin treatment and had a recording of hypoglycemia in the same period. In the matched retrospective cohort study, exposed patients (who experienced hypoglycemia in hospital) were case-matched with patients who did not experience hypoglycemia during admission (unexposed). Generalized linear regression was used to estimate LoS. Risk of all-cause mortality was evaluated via logistic regression. RESULTS: In the retrospective cohort study (1131 patients), mean LoS was 5.46 (95% CI 4.62 to 6.45) days for type 1 diabetes, and 5.04 (95% CI 4.46 to 5.71) days for type 2 diabetes. Mean cost per admission was £1034 (95% CI £855 to £1253). In the matched retrospective cohort study (1079 pairs of patients), exposed patients had a mean LoS of 11.91 days (95% CI 10.96 to 12.94 days) versus 4.80 (95% CI 4.41 to 5.23) for unexposed patients, p<0.0001. Exposed patients had a higher mortality risk compared with unexposed patients (OR 1.439 (95% CI 1.060to 1.952), p=0.0195). Total average per-patient cost for exposed patients was GBP (£)2235, 40% (p<0.0001) higher than total average admission cost in unexposed patients. CONCLUSIONS: Hypoglycemia has a significant negative impact on patient outcomes, healthcare resource use, and expenditure.

Estimating the Incidence and Prevalence of Chronic Hepatitis C Infection in Taiwan Using Back Projection.

OBJECTIVE: Hepatitis C virus (HCV) infection is the leading cause of liver disease, and Taiwan has among the highest prevalence of HCV infection in the general population in Northeast Asia, estimated at between 2% and 4%. The aim of this study was to estimate the number of patients living with chronic HCV infection in Taiwan and quantify the expected numbers in each of the five Metavir fibrosis stages. METHODS: We applied a back-projection approach, using observed hepatocellular carcinoma incidence between 1979 and 2008 and a smoothed Expectation-Maximization algorithm to maximize a Poisson likelihood to estimate the previous incidence of HCV infection. The algorithm was coded in Excel and combined with the MOdelling the NAtural histoRy and Cost-effectiveness of Hepatitis model (a hepatitis C natural history markov model) to predict the past and future numbers in each Metavir fibrosis stage. RESULTS: Incident cases were predicted to have peaked in 1972 at 56,634 annually, with the prevalence peaking in 1986 at 763,737 infections and falling to 578,203 infections in 2012. It was estimated that in 2012, 127,795 (23.0%), 105,545 (19.0%), 81,211 (14.6%), 123,939 (22.3%), and 116,823 (21.1%) subjects were in fibrosis stages F0, F1, F2, F3, and F4, respectively. DISCUSSION: Our study provides HCV infection prevalence estimates, stratified by Metavir fibrosis stage, in Taiwan for 2012. This has potential implications for budget planning, particularly with the availability of emerging therapies because fibrosis stage is predictive of both rapid and sustained virological response; therefore, planning expected treatment response in a given population could be enhanced with this additional information.

Switching from premixed insulin to glargine-based insulin regimen improves glycaemic control in patients with type 1 or type 2 diabetes: a retrospective primary-care-based analysis.

BACKGROUND: Insulin glargine (glargine) and premixed insulins (premix) are alternative insulin treatments. This analysis evaluated glycaemic control in 528 patients with type 1 (n = 183) or type 2 (n = 345) diabetes, after switching from premix to a glargine-based regimen, using unselected general practice (GP) data. METHODS: Data for this retrospective observational analysis were extracted from a UK GP database (The Health Improvement Network). Patients were required to have at least 12 months of available data, before and after, switching from premix to a glargine-based regimen. The principal analysis was the change in HbA1c after 12 months of treatment with glargine; secondary analyses included change in weight, bolus usage and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable assessment of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. RESULTS: Both cohorts showed significant reduction in mean HbA1c 12 months after the switch: by -0.67% (p < 0.001) in the type 1 cohort and by -0.53% (p < 0.001) in the type 2 cohort (adjusted data). The size of HbA1c improvement was positively correlated with baseline HbA1c; patients with a baseline HbA1c > or = 10% had the greatest mean reduction in HbA1c, by -1.7% (p < 0.001) and -1.2% (p < 0.001), respectively. The proportion of patients receiving co-bolus prescriptions increased in the type 1 (mean 24.6% to 95.1%, p < 0.001) and type 2 (mean 16.2% to 73.9%, p < 0.001) cohorts. There was no significant change in weight in either cohort. Total mean insulin use increased in type 2 diabetes patients (from 0.67 +/- 1.35 U/Kg to 0.88 +/- 1.33 U/Kg, p < 0.001) with a slight decrease in type 1 diabetes patients (from 1.04 +/- 2.51 U/Kg to 0.98 +/- 2.58 U/Kg, p < 0.001). CONCLUSION: In everyday practice, patients with type 1 or type 2 diabetes inadequately controlled by premix insulins experienced significant improvement in glycaemic control over 12 months after switching to a glargine-based insulin regimen. These findings support the use of a basal-bolus glargine-based regimen in patients poorly controlled on premix.

Improved glycaemic control by switching from insulin NPH to insulin glargine: a retrospective observational study.

BACKGROUND: Insulin glargine (glargine) and insulin NPH (NPH) are two basal insulin treatments. This study investigated the effect on glycaemic control of switching from a NPH-based regimen to a glargine-based regimen in 701 patients with type 1 (n= 304) or type 2 (n= 397) diabetes, using unselected primary care data. METHODS: Data for this retrospective observational study were extracted from a UK primary care database (The Health Improvement Network). Patients were required to have at least 12 months of data before and after switching from NPH to glargine. The principal analysis was the change in HbA(1c) after 12 months treatment with glargine; secondary analyses included change in weight and total daily insulin dose. Inconsistent reporting of hypoglycemic episodes precludes reliable reporting of this outcome. Multivariate analyses were used to adjust for baseline characteristics and confounding variables. RESULTS: After adjustment, both diabetic cohorts showed statistically significant reductions in mean HbA(1c) 12 months after the switch, by 0.38% (p < 0.001) in type 1 patients and 0.31% (p < 0.001) in type 2 patients. Improvement in HbA1c was positively correlated with baseline HbA(1c); patients with baseline HbA(1c) > or = 8% had reductions of 0.57% (p < 0.001) and 0.47% (p < 0.001), respectively. There was no significant change in weight or total daily insulin dose while on glargine. The majority of patients received a basal-bolus regimen prior to and after the switch (mean 79.3% before and 77.2% after switch in type 1 patients, and 80.4% and 76.8%, respectively in type 2 patients, p > 0.05). CONCLUSION: In routine clinical practice, switching from NPH to glargine provides the opportunity for improving glycaemic control in diabetes patients inadequately controlled by NPH.

Cost-saving treatment strategies in in vitro fertilization: a combined economic evaluation of two large randomized clinical trials comparing highly purified human menopausal gonadotropin and recombinant follicle-stimulating hormone alpha.

OBJECTIVE: To assess the cost-effectiveness of two gonadotropin treatments that are available in the United Kingdom in light of limited public funding and the fundamental role of costs in IVF treatment decisions. DESIGN: An economic evaluation based on two large randomized clinical trials in IVF patients using a simulation model. SETTING: Fifty-three fertility clinics in 13 European countries and Israel. PATIENT(S): Women indicated for treatment with IVF (N = 986), aged 18-38, participating in double-blind, randomized controlled trials. INTERVENTION(S): Highly purified menotropin (HP-hMG, Menopur) or recombinant follitropin alpha (rFSH, Gonal-F). MAIN OUTCOME MEASURE(S): Cost per IVF cycle and cost per live birth for HP-hMG and rFSH alpha. RESULT(S): HP-hMG was more effective and less costly versus rFSH for both IVF cost per live birth and for IVF cost per baby (incremental cost-effectiveness ratio was negative). The mean costs per IVF treatment for HP-hMG and rFSH were 2408 pounds (95% confidence interval [CI], 2392 pounds, 2421 pounds) and 2660 pounds (95% CI 2644 pounds, 2678 pounds), respectively. The mean cost saving of 253 pounds per cycle using HP-hMG allows one additional cycle to be delivered for every 9.5 cycles. CONCLUSION(S): Treatment with HP-hMG was dominant compared with rFSH in the United Kingdom. Gonadotropin costs should be considered alongside live-birth rates to optimize outcomes using scarce health-care resources.

Evaluation of the cost effectiveness of exenatide versus insulin glargine in patients with sub-optimally controlled type 2 diabetes in the United Kingdom.

OBJECTIVE: Exenatide belongs to a new therapeutic class in the treatment of diabetes (incretin mimetics), allowing glucose-dependent glycaemic control in type 2 diabetes. Randomised controlled trial data suggest that exenatide is as effective as insulin glargine at reducing HbA1c in combination therapy with metformin and sulphonylureas; with reduced weight but higher incidence of adverse gastrointestinal events. The objective of this study is to evaluate the cost effectiveness of exenatide versus insulin glargine using RCT data and a previously published model of type 2 diabetes disease progression that is based on the United Kingdom Prospective Diabetes Study; the perspective of the health-payer of the United Kingdom National Health Service. METHODS: The study used a discrete event simulation model designed to forecast the costs and health outcome of a cohort of 1,000 subjects aged over 40 years with sub-optimally-controlled type 2 diabetes, following initiation of either exenatide, or insulin glargine, in addition to oral hypoglycaemic agents. Sensitivity analysis for a higher treatment discontinuation rate in exenatide patients was applied to the cohort in three different scenarios; (1) either ignored or (2) exenatide-failures excluded or (3) exenatide-failures switched to insulin glargine. Analyses were undertaken to evaluate the price sensitivity of exenatide in terms of relative cost effectiveness. Baseline cohort profiles and effectiveness data were taken from a published randomised controlled trial. RESULTS: The relative cost-effectiveness of exenatide and insulin glargine was tested under a variety of conditions, in which insulin glargine was dominant in all cases. Using the most conservative of assumptions, the cost-effectiveness ratio of exenatide vs. insulin glargine at the current UK NHS price was -29,149 pounds/QALY (insulin glargine dominant) and thus exenatide is not cost-effective when compared with insulin glargine, at the current UK NHS price. CONCLUSION: This study evaluated the relative cost effectiveness of insulin glargine versus exenatide in the management of type 2 diabetes using a published model. Given no significant difference in glycaemic control and applying the additional effectiveness of exenatide over insulin glargine, with respect to weight loss, and using the current UK NHS prices, insulin glargine was found to be dominant over exenatide in all modelled scenarios. With current clinical evidence, exenatide does not appear to represent a cost-effective treatment option for patients with type 2 diabetes when compared to insulin glargine.

The cost of renal dialysis in a UK setting--a multicentre study.

BACKGROUND: The UK National Health Service (NHS) will fund renal services using Payment by Results (PbR), from 2009. Central to the success of PbR will be the creation of tariffs that reflect the true cost of medical services. We have therefore estimated the cost of different dialysis modalities in the Cardiff and Vale NHS Trust and six other hospitals in the UK. METHODS: We used semi-structured interviews with nephrologists, head nurses and business managers to identify the steps involved in delivering the different dialysis modalities. We assigned costs to these using published figures or suppliers' published price lists. The study used mixed costing methods. Dialysis costs were estimated by a combination of microcosting and a top-down approach. Where we did not have access to detailed accounts, we applied values for Cardiff. RESULTS: The most efficient modalities were automated peritoneal dialysis (APD) and continuous ambulatory peritoneal dialysis (CAPD), the mean annual costs of which were pound21 655 and pound15 570, respectively. Hospital-based haemodialysis (HD) cost pound35 023 per annum and satellite-unit-based HD cost pound32 669. The cost of home-based HD was pound20 764 per year (based on data from only one unit). The main cost drivers for PD were the costs of solutions and management of anaemia. For HD they were costs of disposables, nursing, the overheads associated with running the unit and management of anaemia. CONCLUSIONS: Renal tariffs for PbR need to reflect the true cost of dialysis provision if choices about modalities are not to be influenced by erroneous estimates of cost. Knowledge of the true costs of modalities will also maximize the number of established renal failure patients treated by dialysis within the limited funds available from the NHS.

An economic evaluation of highly purified HMG and recombinant FSH based on a large randomized trial.

Public funding for IVF is increasingly being challenged by health authorities in an attempt to minimize health service costs. In light of treatment rationing, the need to consider costs in relation to outcomes is paramount. To assess the cost implications of gonadotrophin treatment options, an economic evaluation comparing highly purified human menopausal gonadotrophin (HP-HMG) and recombinant FSH (rFSH) has been conducted. The analysis is based on individual patient data from a large randomized controlled trial (n = 731) in a long agonist IVF protocol. The economic evaluation uses a discrete event simulation model to assess treatment costs in relation to live births for both treatments based on published UK costs. After one cycle the mean costs per IVF treatment for HP-HMG and rFSH were pound2396 (95% CI pound2383-2414) and pound2633 ( pound2615-2652), respectively. The average cost-saving of pound237 per IVF cycle using HP-HMG allows one additional cycle to be delivered for every 10 cycles. With maternal and neonatal costs applied, the median cost per IVF baby delivered with HP-HMG was pound8893 compared with pound11,741 for rFSH (P < 0.001). The cost-saving potential of HP-HMG in IVF was still apparent after varying critical cost parameters in the probabilistic sensitivity analysis.

Pulse pressure predicts cardiovascular risk in patients with type 2 diabetes mellitus.

BACKGROUND: Pulse pressure (PP), a marker of arterial stiffness, is a better predictor of coronary heart disease (CHD) risk than systolic blood pressure (SBP) or diastolic blood pressure (DBP) in older adults. Whether this is also true in subjects with type 2 diabetes, who are at increased risk for cardiovascular disease, is unknown. METHODS: Data on 2911 type 2 diabetic subjects relating to blood pressure (BP), other risk factors, and cardiovascular events were abstracted from The Cardiff Diabetes Database. Logistic regression was used to assess the relationship among BP components and the risk of CHD, cerebrovascular (CVD), and peripheral vascular (PVD) events after correction for age, gender, cholesterol, and smoking status. RESULTS: In the 4-year follow-up period there were 574 CHD, 168 CVD, and 157 PVD events. Both PP and SBP, but not DBP, were positively associated with the risk of all event types. However, PP emerged as the best predictor of CHD events, and SBP as the best predictor of CVD and PVD events. Total and HDL-cholesterol were the most important variables associated with PP after age. CONCLUSIONS: In summary, PP is a better predictor of CHD events than SBP in persons with type 2 diabetes, but the converse is true for CVD and PVD.