A model to estimate the lifetime health outcomes of patients with Type 2 diabetes: the United Kingdom Prospective Diabetes Study (UKPDS) Outcomes Model (UKPDS no. 68)

<i>Aims/hypothesis</i> The aim of this study was to develop a simulation model for Type 2 diabetes that can be used to estimate the likely occurrence of major diabetes-related complications over a lifetime, in order to calculate health economic outcomes such as quality-adjusted life expectancy. <i>Methods</i> Equations for forecasting the occurrence of seven diabetes-related complications and death were estimated using data on 3642 patients from the United Kingdom Prospective Diabetes Study (UKPDS). After examining the internal validity, the UKPDS Outcomes Model was used to simulate the mean difference in expected quality-adjusted life years between the UKPDS regimens of intensive and conventional blood glucose control. <i>Results</i> The models forecasts fell within the 95% confidence interval for the occurrence of observed events during the UKPDS follow-up period. When the model was used to simulate event history over patients lifetimes, those treated with a regimen of conventional glucose control could expect 16.35 undiscounted quality-adjusted life years, and those receiving treatment with intensive glucose control could expect 16.62 quality-adjusted life years, a difference of 0.27 (95% CI: –0.48 to 1.03). <i>Conclusions/interpretations</i> The UKPDS Outcomes Model is able to simulate event histories that closely match observed outcomes in the UKPDS and that can be extrapolated over patients lifetimes. Its validity in estimating outcomes in other groups of patients, however, remains to be evaluated. The model allows simulation of a range of long-term outcomes, which should assist in informing future economic evaluations of interventions in Type 2 diabetes

The impact of diabetes-related complications on healthcare costs: results from the United Kingdom Prospective Diabetes Study (UKPDS Study No. 65)

<b>Aims</b> To develop a model for estimating the immediate and long-term healthcare costs associated with seven diabetes-related complications in patients with Type 2 diabetes participating in the UK Prospective Diabetes Study (UKPDS). <b>Methods</b> The costs associated with some major complications were estimated using data on 5102 UKPDS patients (mean age 52.4 years at diagnosis). In-patient and out-patient costs were estimated using multiple regression analysis based on costs calculated from the length of admission multiplied by the average specialty cost and a survey of 3488 UKPDS patients’ healthcare usage conducted in 1996–1997. <b>Results</b> Using the model, the estimate of the cost of first complications were as follows: amputation £8459 (95% confidence interval £5295, £13 200); non-fatal myocardial infarction £4070 (£3580, £4722); fatal myocardial infarction £1152 (£941, £1396); fatal stroke £3383 (£1935, £5431); non-fatal stroke £2367 (£1599, £3274); ischaemic heart disease £1959 (£1467, £2541); heart failure £2221 (£1690, £2896); cataract extraction £1553 (£1320, £1855); and blindness in one eye £872 (£526, £1299). The annual average in-patient cost of events in subsequent years ranged from £631 (£403, £896) for heart failure to £105 (£80, £142) for cataract extraction. Non-in-patient costs for macrovascular complications were £315 (£247, £394) and for microvascular complications were £273 (£215, £343) in the year of the event. In each subsequent year the costs were, respectively, £258 (£228, £297) and £204 (£181, £255). <b>Conclusions</b> These results provide estimates of the immediate and long-term healthcare costs associated with seven diabetes-related complications

Diminishing Efficacy of Combination Therapy, Response-Heterogeneity, and Treatment Intolerance Limit the Attainability of Tight Risk Factor Control in Patients with Diabetes

To evaluate the attainability of tight risk factor control targets for three diabetes risk factors and to assess the degree of polypharmacy required.National Health and Nutrition Examination Survey-III.We simulated a strategy of “treating to targets,” exposing subjects to a battery of treatments until low-density lipoprotein (LDL)-cholesterol (100 mg/dL), hemoglobin A1c (7 percent), and blood pressure (130/80 mm Hg) targets were achieved or until all treatments had been exhausted. Regimens included five statins of increasing potency, four A1c-lowering therapies, and eight steps of antihypertensive therapy.We selected parameter estimates from placebo-controlled trials and meta-analyses.Under ideal efficacy conditions, 77, 64, and 58 percent of subjects achieved the LDL, A1c, and blood pressure targets, respectively. Successful control depended highly on a subject's baseline number of treatments. Using the least favorable assumptions of treatment tolerance, success rates were 11–17 percentage points lower. Approximately 57 percent of subjects required five or more medication classes.A significant proportion of people with diabetes will fail to achieve targets despite using high doses of multiple, conventional treatments. These findings raise concerns about the feasibility and polypharmacy burden needed for tight risk factor control, and the use of measures of tight control to assess the quality of care for diabetes.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/79268/1/j.1475-6773.2009.01075.x.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/79268/2/HESR_1075_sm_appendix.pd

The management of type 2 diabetes with fixed‐ratio combination insulin degludec/liraglutide (IDegLira) versus basal‐bolus therapy (insulin glargine U100 plus insulin aspart): a short‐term cost‐effectiveness analysis in the UK setting

Aim: To evaluate the cost‐effectiveness of IDegLira versus basal‐bolus therapy (BBT) with insulin glargine U100 plus up to 4 times daily insulin aspart for the management of type 2 diabetes in the UK. Methods: A Microsoft Excel model was used to evaluate the cost‐utility of IDegLira versus BBT over a 1‐year time horizon. Clinical input data were taken from the treat‐to‐target DUAL VII trial, conducted in patients unable to achieve adequate glycaemic control (HbA1c <7.0%) with basal insulin, with IDegLira associated with lower rates of hypoglycaemia and reduced body mass index (BMI) in comparison with BBT, with similar HbA1c reductions. Costs (expressed in GBP) and event‐related disutilities were taken from published sources. Extensive sensitivity analyses were performed. Results: IDegLira was associated with an improvement of 0.05 quality‐adjusted life years (QALYs) versus BBT, due to reductions in non‐severe hypoglycaemic episodes and BMI with IDegLira. Costs were higher with IDegLira by GBP 303 per patient, leading to an incremental cost‐effectiveness ratio (ICER) of GBP 5924 per QALY gained for IDegLira versus BBT. ICERs remained below GBP 20 000 per QALY gained across a range of sensitivity analyses. Conclusions: IDegLira is a cost‐effective alternative to BBT with insulin glargine U100 plus insulin aspart, providing equivalent glycaemic control with a simpler treatment regimen for patients with type 2 diabetes inadequately controlled on basal insulin in the UK

Demographics, insulin use and clinical targets in type 2 diabetes insulin users: comparison of a local integrated diabetes service vs a UK-wide cohort

Insulin-treated patients with type 2 diabetes require specialist multidisciplinary input to achieve treatment targets. We compared the demographics, achievement of combined NICE targets for HbA1c (≤7.5%), blood pressure (<140/80mmHg) and total cholesterol (<4mmol/L), and insulin use between patients from a local integrated diabetes service with those from a representative UK population. A cross-sectional evaluation of individual patient data from six randomly-selected primary care practices in Erewash (Integrated) Diabetes Service was compared with The Health Improvement Network (THIN) UK primary care database. Baseline age (61.5 years vs 65.8 years; p < 0.0001) and duration of insulin use (4.3 vs 6.3 years; p < 0.0001) use were lower in the THIN cohort. Mean HbA1c was similar between the two cohorts but weight, blood pressure, total and LDL cholesterol were significantly lower in the Erewash population compared with THIN. The combined achievement of HbA1c, total cholesterol and blood pressure was 17.5% in the Erewash cohort compared with 9.6% in the THIN cohort (p < 0.0001). There was a higher proportion of insulin users on basal-bolus than on premix in the Erewash cohort (89.3% vs 10.7%) compared with THIN (59.0% vs 41.1%). The proportion of patients who received concurrent oral glucose-lowering therapies in the Erewash integrated service was lower, except for SGLT2 inhibitors (2.5% in the Erewash cohort vs 0.5% in THIN; p < 0.0001). This model of an integrated diabetes service appears to confer better achievement for the NICE defined clinical targets compared with the THIN cohort. Further studies are required to investigate the impact of this service model on health economics, patient pathway and patient experience. Copyright © 2017 John Wiley & Sons

Liraglutide, a once-daily human glucagon-like peptide 1 analogue, provides sustained improvements in glycaemic control and weight for 2 years as monotherapy compared with glimepiride in patients with type 2 diabetes

Aims: Most treatments for type 2 diabetes fail over time, necessitating combination therapy. We investigated the safety, tolerability and efficacy of liraglutide monotherapy compared with glimepiride monotherapy over 2 years

Skin microvascular vasodilatory capacity in offspring of two parents with Type 2 diabetes

Aims&lt;br/&gt; Microvascular dysfunction occurs in Type 2 diabetes and in subjects with fasting hyperglycaemia. It is unclear whether this dysfunction relates to dysglycaemia. This study investigated in normogylcaemic individuals whether a genetic predisposition to diabetes, or indices of insulin resistance including endothelial markers, were associated with impaired microvascular function.&lt;br/&gt; Methods&lt;br/&gt; Maximum microvascular hyperaemia to local heating of the skin was measured using laser Doppler flowmetry in 21 normoglycaemic subjects with no family history of diabetes (Group 1) and 21 normoglycaemic age, sex and body mass index-matched offspring of two parents with Type 2 diabetes (Group 2). &lt;br/&gt;Results&lt;br/&gt; Although Group 2 had normal fasting plasma glucose and glucose tolerance tests, the 120-min glucose values were significantly higher at 6.4 (5.3-6.6) mmol/l (median (25th-75th centile)) than the control group at 4.9 (4.6-5.9) mmol/l (P=0.005) and the insulinogenic index was lower at 97.1 (60.9-130.8) vs. 124.0 (97.2-177.7) (P=0.027). Skin maximum microvascular hyperaemia (Group 1: 1.56 (1.39- 1.80) vs. Group 2: 1.53 (1.30-1.98) V, P=0.99) and minimum microvascular resistance which normalizes the hyperaemia data for blood pressure (Group 1: 52.0 (43.2-67.4) vs. Group 2: 56.0 (43.7-69.6) mmHgN, P=0.70) did not differ in the two groups. Significant positive associations occurred between minimum microvascular resistance and indices of the insulin resistance syndrome; plasminogen activator inhibitor type 1 (R-s=0.46, P=0.003), t-PA (R-s=0.36, P=0.03), total cholesterol (R-s=0.35, P=0.02), and triglyceride concentration (R-s=0.35, P=0.02), and an inverse association with insulin sensitivity (R-s=-0.33, P=0.03).&lt;br/&gt; Conclusions&lt;br/&gt; In normoglycaemic adults cutaneous microvascular vasodilatory capacity is associated with features of insulin resistance syndrome, particularly with plasminogen activator inhibitor type 1. A strong family history of Type 2 diabetes alone does not result in impairment in the maximum hyperaemic response

Prevalence of diabetic peripheral neuropathy and relation to glycemic control therapies at baseline in the BARI 2D cohort

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74968/1/j.1529-8027.2009.00200.x.pd

Triple Combination Therapy Using Metformin, Thiazolidinedione, and a GLP-1 Analog or DPP-IV Inhibitor in Patients with Type 2 Diabetes Mellitus

Although there is no HbA1c threshold for cardiovascular risk, the American Diabetic Association-recommended goal of HbA1c < 7.0% appears to be unacceptably high. To achieve an optimal HbA1c level goal of 6.0% or less, a high dosage of sulfonylureas and insulin would be required; the trade-off would be the common adverse effects of hypoglycemia and weight gain. In contrast, hypoglycemia is uncommon with insulin sensitizers and GLP-1 analogs, allowing the physician to titrate these drugs to maximum dosage to reduce HbA1c levels below 6.0% and they have been shown to preserve β-cell function. Lastly, weight gain is common with sulfonylurea and insulin therapy, whereas GLP-1 analogs induce weight loss and offset the weight gain associated with TZDs. A treatment paradigm shift is recommended in which combination therapy is initiated with diet/exercise, metformin (which has antiatherogenic effects and improves hepatic insulin sensitivity), a TZD (which improves insulin sensitivity and preserves β-cell function with proven durability), and a GLP-1 analog (which improves β, α-cell function and promotes weight loss) or a dipeptidyl peptidase IV inhibitor in patients with type 2 diabetes mellitus