Effects of Losartan-based therapy on the incidence of end-stage renal disease and associated costs in type 2 diabetes mellitus: A retrospective cost-effectiveness analysis in the United Kingdom

AbstractBackground:In the Reduction of Endpoints in Non-Insulin-Dependent Diabetes Mellitus with the Angiotensin II Antagonist Losartan (RENAAL) study, the primary composite end point was the 2-fold increase in baseline serum creatinine concentration, the development of end-stage renal disease (ESRD), or death. The effects of losartan used for the prevention or delay of progression of diabetic nephropathy to ESRD were compared with those of conventional anti-hypertensive treatment (control) (calcium channel blockers, diuretics, α-blockers, β-blockers, and centrally acting agents), but not angiotensin-converting enzyme (ACE) inhibitors or angiotensin II antagonists (AIIAs), in 1513 adults with type 2 diabetes mellitus (DM-2) and nephropathy. Both treatment groups received conventional antihypertensive therapy (calcium channel blockers, diuretics, α-blockers, β-blockers, and/or centrally acting agents). ACE inhibitors and AIIAs were not allowed during the study period. The relative risk (RR) for composite outcome was 25% less, and the RR for ESRD was 28% less, in the losartantreated group compared with the control group.Objective:The aim of this retrospective cost-effectiveness analysis was to use data from the RENAAL study to determine the survival benefits and lifetime direct medical costs of a losartan-based regimen for the prevention of ESRD in patients with DM-2 and nephropathy in the setting of the UK National Health Service (NHS).Methods:This analysis used life-years saved as the effectiveness measure. The effect of losartan-based treatment on ESRD risk was confined to the trial period (3.5 years). However, survival and the lifetime direct medical costs of managing ESRD were projected beyond the trial period to incorporate the full effects of ESRD on survival and resource use. The effect of altering key variables was examined using 1-way sensitivity analyses.Results:ESRD-related costs were significantly lower in patients receiving losartan-based treatment compared with those in the control group (savings per patient, 7390 [95% CI, 11,366-3414; P< 0.001] [1 = US −$1.75]). Incorporation of the cost of losartan into the assessment found reduced net costs (savings per patient, 6622 [95% CI, 10,591-2653; P= 0.001]). The projected mean number of life years saved due to ESRD risk reduction with losartan was 0.44 years (95% CI, 0.16–0.71; P = 0.002). Losartan treatment was found to save costs in all cases, even if the cost of renal replacement therapy for patients with ESRD was reduced by 50%.Conclusion:In this retrospective cost-effectiveness analysis using data from the RENAAL study, losartan-based treatment for the prevention or delay of progression of diabetic nephropathy to ESRD in patients with DM-2 and nephropathy was found to be potentially cost saving compared with conventional anti-hypertensive therapy from the perspective of the UK NHS

Lower risk of hypoglycaemia and greater odds for weight loss with initiation of insulin detemir compared with insulin glargine in Turkish patients with type 2 diabetes mellitus: local results of a multinational observational study

BACKGROUND: The purpose of this analysis is to evaluate the safety and effectiveness of insulin initiation with once-daily insulin detemir (IDet) or insulin glargine (IGlar) in real-life clinical practice in Turkish patients with type 2 diabetes mellitus (T2DM). METHODS: This was a 24-week multinational observational study of insulin initiation in patients with T2DM. RESULTS: The Turkish cohort (n = 2886) included 2395 patients treated with IDet and 491 with IGlar. The change in glycosylated haemoglobin (HbA(1c)) from the pre-insulin levels was -2.21% [95% confidence interval (CI) -2.32, -2.09] in the IDet group and -1.88% [95% CI -2.17, -1.59] in the IGlar group at the final visit. The incidence rate of minor hypoglycaemia increased in both groups from the pre-insulin to the final visit (+0.66 and +2.23 events per patient year in the IDet and IGlar groups, respectively). Weight change in the IDet group was -0.23 kg [95% CI -0.49, 0.02 kg], and +1.55 kg [95% CI 1.11, 2.00 kg] in the IGlar group. Regression analysis with adjustment for previously identified confounders (age, gender, duration of diabetes, body mass index, previous history of hypoglycaemia, microvascular disease, number and change in oral anti-diabetic drug therapy, HbA(1c) at baseline and insulin dose) identified an independent effect of insulin type (IDet versus IGlar) with a risk of at least one episode of hypoglycaemia (odds ratio (OR): 0.33 [95% CI 0.21, 0.52], p <0.0001), and weight loss ≥1 kg (OR: 1.75 [95% CI 1.18, 2.59], p = 0.005), but not on HbA(1c) (+0.05% [95% CI -0.15, 0.25%], p = 0.6). CONCLUSIONS: Initiation of basal insulin analogues, IDet and IGlar, were associated with clinically significant glycaemic improvements. A lower risk of minor hypoglycaemia and greater odds of weight loss ≥1 kg was observed with IDet compared with IGlar. TRIAL REGISTRATION: NCT00825643 and NCT0074051

Safety, Efficacy and Cost Effectiveness of Individualised Screening for Diabetic Retinopathy: The ISDR Randomised Controlled Trial

Background: varying diabetic retinopathy (DR) screening intervals, informed by personal risk-levels, empowers people with diabetes (PWD), and offers reallocation of resources to high risk groups, while addressing the increasing prevalence of diabetes. Safety data on extending intervals is minimal. We evaluated the safety, efficacy and cost effectiveness of individualised risk-based variable-interval population screening compared to usual care, with design input from PWD.Methods: two-arm, parallel assignment, equivalence randomised controlled trial (minimum 2 year follow-up) in PWD aged ≥12 years registered with one English screening programme. Randomisation was 1:1 to individualised screening (6, 12 or 24 months for high, medium and low risk) determined by a risk calculation engine, using local demographic, screening and clinical data, or to annual screening (control). Primary outcome was attendance (safety). A secondary safety outcome was the development of sight threatening DR (STDR). Cost effectiveness was evaluated within a 2 year time horizon from NHS and societal perspectives.Findings: 4534 participants were randomised, 2265 to the individualised and 2269 to the control arm. Attendance rates at first follow-up were equivalent between individualised (1754/2097, 83·6%) and control (1883/2224, 84·7%) arms (difference -1·0, 95% CI -3·2 to 1·2). STDR detection rates were non-inferior: individualised 1·4%, control 1·7% (- 0·3, -1·1 to 0·5). Sensitivity analyses confirmed findings. Incremental QALYs/person were non-significant: EQ-5D-5L 0·035 (CI -0·04, 0·13), HUI3 0·009 (CI -0·09, 0·10). Incremental cost savings were £21·31 (CI 15·24, 26·79)/person for the NHS and £28·87 (CI 21·08, 35·78) including societal costs. 43·2% fewer screening appointments were required in the individualised arm.Interpretation: stakeholders involved in diabetes care can be reassured by this largest ophthalmic RCT in DR screening to date that extended and individualised risk-based intervals can be safely and cost effectively introduced in established screening programmes

Safety and cost-effectiveness of individualised screening for diabetic retinopathy: the ISDR open-label, equivalence RCT

Aims/hypothesis Using variable diabetic retinopathy screening intervals, informed by personal risk levels, offers improved engagement of people with diabetes and reallocation of resources to high-risk groups, while addressing the increasing prevalence of diabetes. However, safety data on extending screening intervals are minimal. The aim of this study was to evaluate the safety and cost-effectiveness of individualised, variable-interval, risk-based population screening compared with usual care, with wide ranging input from individuals with diabetes. Methods This was a two-arm, parallel-assignment, equivalence RCT (minimum 2 year follow-up) in individuals with diabetes aged 12 years or older registered with a single English screening programme. Participants were randomly allocated 1:1 at baseline to individualised screening at 6, 12 or 24 months for those at high, medium and low risk, respectively, as determined at each screening episode by a risk-calculation engine using local demographic, screening and clinical data, or to annual screening (control group). Screening staff and investigators were observer-masked to allocation and interval. Data were collected within the screening programme. The primary outcome was attendance (safety). A secondary safety outcome was the development of sight-threatening diabetic retinopathy. Cost-effectiveness was evaluated within a 2 year time horizon from National Health Service and societal perspectives. Results A total of 4534 participants were randomised. After withdrawals, there were 2097 participants in the individualised screening arm and 2224 in the control arm. Attendance rates at first follow-up were equivalent between the two arms (individualised screening 83.6%; control arm 84.7%; difference −1.0 [95% CI −3.2, 1.2]), while sight-threatening diabetic retinopathy detection rates were non inferior in the individualised screening arm (individualised screening 1.4%, control arm 1.7%; difference −0.3 [95% CI −1.1, 0.5]). Sensitivity analyses confirmed these findings. No important adverse events were observed. Mean differences in complete case quality adjusted life-years (EuroQol Five-Dimension Questionnaire, Health Utilities Index Mark 3) did not significantly differ from zero

Incidence of sight-threatening diabetic retinopathy in an established urban screening programme: An 11-year cohort study

Aims: systematic annual screening to detect sight-threatening diabetic retinopathy (STDR) is established in the United Kingdom. We designed an observational cohort study to provide up-to-date data for policy makers and clinical researchers on incidence of key screening endpoints in people with diabetes attending one screening programme running for over 30 years.Methods: all people with diabetes aged ≥12 years registered with general practices in the Liverpool health district were offered inclusion. Data sources comprised: primary care (demographics, systemic risk factors), Liverpool Diabetes Eye Screening Programme (retinopathy grading), Hospital Eye Services (slit lamp biomicroscopy assessment of screen positives).Results: 133,366 screening episodes occurred in 28,384 people over 11 years. Overall incidences were: screen positive 6.7% (95% CI 6.5–6.8), screen positive for retinopathy 3.1% (3.0–3.1), unassessable images 2.6% (2.5–2.7), other significant eye diseases 1.0% (1.0–1.1). 1.6% (1.6–1.7) had sight-threatening retinopathy confirmed by slit lamp biomicroscopy. The annual incidence of screen positive and screen positive for retinopathy showed consistent declines from 8.8%–10.6% and 4.4%–4.6% in 2007/09 to 4.4%–6.8% and 2.3%–2.9% in 2013/17, respectively. Rates of STDR (true positive) were consistently below 2% after 2008/09. Screen positive rates were higher in first time attenders (9.9% [9.4–10.2] vs. 6.1% [6.0–6.2]) in part due to ungradeable images (4.1% vs. 2.3%) and other eye disease (2.4% vs. 0.8%). 4.5% (3.9–5.2) of previous non-attenders had sight-threatening retinopathy. Compared with people with type 2 diabetes, those with type 1 disease demonstrated higher rates of screen positive (11.9% vs. 6.0%) and STDR (6.4% vs. 1.2%). Overall prevalence of any retinopathy was 27.2% (27.0–27.4).Conclusions: in an established screening programme with a stable population screen, positive rates show a consistent fall over time to a low level. Of those who are screen positive, fewer than 50% are screen positive for diabetic retinopathy. Most are due to sight threatening maculopathy. The annual incidence of STDR is under 2% suggesting future work on redefining screen positive and supporting extended intervals for people at low risk. Higher rates of screen positive and STDR are seen in first time attenders. Those who have never attended for screening should be specifically targeted.</p

The English National Risk Reduction Programme for Preservation of Sight in Diabetes

Introduction: The National Service Framework for Diabetes has set the first target that all people with diabetes in England will be screened annually for the detection of sight threatening eye disease (STED) by 2007. There is consistent evidence that screening for diabetic retinopathy is effective and treatment modalities have been established which could prevent partial sight and blindness registration in 80-90 % of cases. Methods: The Liverpool Diabetic Eye Study uses a mobile screening system utilising 35 mm, (converting to digital) 3-field fundus photography in all people with diabetes not attending an ophthalmologist. In 1995/1996 we reported detection of STED in 7.4% of cases compared to a rate of 3.7% in 2001/2002, with a sensitivity of 93% and specificity of 94%. The Policy Advisory Group has been formulated with the main aim to establish a cost effective national STED screening programme. There is currently inconsistency in service provision for diabetic retinopathy screening in the UK, ranging from organised services employing cost effective technology to ad hoc services with no central organisation. Two models of service delivery are recommended which adhere to the National Screening Committee’s requirements for a screening programme: diabetic retinopathy screening using digital mydriatic retinal photography in both community and secondary care settings with image reading by accredited individuals; diabetic retinopathy screening using indirect slit lamp mydriatic retinal biomicroscopy performed by trained personnel in both community and secondary care settings. Discussion: Increased funding for resources is required in some health authority regions in order to establish a screening programme. It is hoped that all people with diabetes will be screened for STED in order to reduce the burden of diabetic retinopathy in society

Cardiovascular protection with sodium-glucose co-transporter-2 inhibitors in type 2 diabetes: Does it apply to all patients?

Patients with type 2 diabetes (T2D) are at an increased risk of cardiovascular disease (CVD). Cardiovascular risk in these patients should be considered as a continuum, and comprehensive treatment strategies should aim to target multiple disease risk factors. Large-scale clinical trials of sodium-glucose co-transporter-2 (SGLT2) inhibitors have shown an impact on cardiovascular outcomes, including heart failure hospitalization and cardiovascular death, which appears to be independent of their glucose-lowering efficacy. Reductions in major cardiovascular events appear to be greatest in patients with established CVD, particularly those with prior myocardial infarction, but are independent of heart failure or renal risk. Most large-scale trials of SGLT2 inhibitors predominantly include patients with T2D with pre-existing CVD and high cardiovascular risk at baseline, limiting their applicability to patients typically observed in clinical practice. Real-world evidence from observational studies suggests that there might also be beneficial effects of SGLT2 inhibitors on heart failure hospitalization and all-cause mortality in various cohorts of lower risk patients. The most common adverse events reported in clinical and observational studies are genital infections; however, the overall risk of these events appears to be low and easily managed. Similar safety profiles have been reported for elderly and younger patients. There is still some debate regarding the safety of canagliflozin in patients at high risk of fracture and amputation. Outstanding questions include specific patterns of cardiovascular protection according to baseline risk