Real-World Analysis of Long-Acting and NPH-Containing Insulins on Glycemic Control.

Introduction Affordability of insulin products has become a concern in the past several years as the average price of various insulin products has increased. While awaiting legislation at the federal level that would address issues leading to high insulin costs, providers may have shifted prescribing practices to prescribe the lowest-priced insulin products to achieve patients' treatment goals. Objective To compare the prevalence of hypoglycemic events between patients receiving lower-cost neutral protamine Hagedorn (NPH)-containing human insulins and higher-cost long-acting insulin analogs in Medicare Part D enrollees within a management services organization, as well as assessing glycemic control and changes in body mass index. Methods This was a multicenter, retrospective study conducted at three primary care clinics. The co-primary outcomes were percent difference of documented mild and severe hypoglycemic events between individuals receiving NPH-containing human insulin and long-acting insulin. Results A total of 72 patients met inclusion criteria and were receiving NPH-containing human insulins or the long-acting insulin analogs, 15 and 57 patients, respectively. Severe hypoglycemic events occurred in 3.5% vs 0% of the long-acting insulin analog and NPH-containing human insulin group, respectively (P = 0.999). Mild hypoglycemic episodes were experienced by 31.6% versus 33.3% of long-acting insulin analog and NPH, respectively (P = 0.539). For secondary outcomes, no difference was observed in glycemic control outcomes across insulin groups. Conclusion Among Medicare Part D patients with type 2 diabetes mellitus, the use of NPH-containing human insulins was not associated with an increased risk of mild or severe hypoglycemia-related episodes or reduced glycemic control compared with long-acting insulin. Study findings suggest that lower-cost, NPH-containing human insulins may be an alternative to higher-cost, long-acting insulin analogs.

Assessment of the Effect of Timing of Insulin Glargine Administration (Bedtime versus Morning) on Glycemic Control in Children with Type 1 Diabetes in Cairo, Egypt: A Single Centre Experience.

BACKGROUND: Diabetes control without developing hypoglycemia is challenging in Type 1 diabetes (T1D) management, with few studies evaluating the effect of insulin glargine timing on glucoregulation. OBJECTIVES: The aim is to compare glycemic control using continuous glucose monitoring (CGM) in children with T1D receiving bedtime versus morning glargine and to assess CGM effect on glycemia. METHODS: This cross-sectional observational study was conducted on 30 pediatric patients with T1D receiving glargine (19 at bedtime and 11 in the morning). CGM sensor was applied for 3-5 days using the I-Pro2 blood glucose sensor. RESULTS: Total daily dose of glargine showed a significant correlation with HbA1C (p=0.006) and percentage of glucose readings within average (p=0.039). HbA1C correlated significantly with time in range (TIR) (p=0.049). Nocturnal hypoglycemia was significantly higher in the bedtime glargine group than in the morning one (p=0.016). The morning glargine group showed better control in terms of lower HbA1C and higher TIR, but these did not reach statistical significance. Follow- up after 3 months revealed significant improvement in the percentage of hyperglycemia, BG readings within average, as well as HbA1c (p:0.001). CONCLUSIONS: Bedtime glargine administration was associated with a higher frequency of occurrence of nocturnal hypoglycemia. No statistically significant difference in glycemic control between both groups was found. CGM use improved glycemic control.

(Ultra-)long-acting insulin analogues for people with type 1 diabetes mellitus.

BACKGROUND: People with type 1 diabetes mellitus (T1DM) need treatment with insulin for survival. Whether any particular type of (ultra-)long-acting insulin provides benefit especially regarding risk of diabetes complications and hypoglycaemia is unknown. OBJECTIVES: To compare the effects of long-term treatment with (ultra-)long-acting insulin analogues to NPH insulin (neutral protamine Hagedorn) or another (ultra-)long-acting insulin analogue in people with type 1 diabetes mellitus. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, Scopus, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform and the reference lists of systematic reviews, articles and health technology assessment reports. We explored the US Food and Drug Administration (FDA) and European Medical Agency (EMA) web pages. We asked pharmaceutical companies, EMA and investigators for additional data and clinical study reports (CSRs). The date of the last search of all databases was 24 August 2020. SELECTION CRITERIA: We included randomised controlled trials (RCTs) with a duration of 24 weeks or more comparing one (ultra-)long-acting insulin to NPH insulin or another (ultra-)long-acting insulin in people with T1DM. DATA COLLECTION AND ANALYSIS: Two review authors assessed risk of bias using the new Cochrane 'Risk of bias' 2 (RoB 2) tool and extracted data. Our main outcomes were all-cause mortality, health-related quality of life (QoL), severe hypoglycaemia, non-fatal myocardial infarction/stroke (NFMI/NFS), severe nocturnal hypoglycaemia, serious adverse events (SAEs) and glycosylated haemoglobin A1c (HbA1c). We used a random-effects model to perform meta-analyses and calculated risk ratios (RRs) and odds ratios (ORs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) and 95% prediction intervals for effect estimates. We evaluated the certainty of the evidence applying the GRADE instrument. MAIN RESULTS: We included 26 RCTs. Two studies were unpublished. We obtained CSRs, clinical study synopses or both as well as medical reviews from regulatory agencies on 23 studies which contributed to better analysis of risk of bias and improved data extraction. A total of 8784 participants were randomised: 2428 participants were allocated to NPH insulin, 2889 participants to insulin detemir, 2095 participants to insulin glargine and 1372 participants to insulin degludec. Eight studies contributing 21% of all participants comprised children. The duration of the intervention varied from 24 weeks to 104 weeks. Insulin degludec versus NPH insulin: we identified no studies comparing insulin degludec with NPH insulin. Insulin detemir versus NPH insulin (9 RCTs): five deaths reported in two studies including adults occurred in the insulin detemir group (Peto OR 4.97, 95% CI 0.79 to 31.38; 9 studies, 3334 participants; moderate-certainty evidence). Three studies with 870 participants reported QoL showing no true beneficial or harmful effect for either intervention (low-certainty evidence). There was a reduction in severe hypoglycaemia in favour of insulin detemir: 171/2019 participants (8.5%) in the insulin detemir group compared with 138/1200 participants (11.5%) in the NPH insulin group experienced severe hypoglycaemia (RR 0.69, 95% CI 0.52 to 0.92; 8 studies, 3219 participants; moderate-certainty evidence). The 95% prediction interval ranged between 0.34 and 1.39. Only 1/331 participants in the insulin detemir group compared with 0/164 participants in the NPH insulin group experienced a NFMI (1 study, 495 participants; low-certainty evidence). No study reported NFS. A total of 165/2094 participants (7.9%) in the insulin detemir group compared with 102/1238 participants (8.2%) in the NPH insulin group experienced SAEs (RR 0.95, 95% CI 0.75 to 1.21; 9 studies, 3332 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 70/1823 participants (3.8%) in the insulin detemir group compared with 60/1102 participants (5.4%) in the NPH insulin group (RR 0.67, 95% CI 0.39 to 1.17; 7 studies, 2925 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin detemir with NPH insulin was 0.01%, 95% CI -0.1 to 0.1; 8 studies, 3122 participants; moderate-certainty evidence. Insulin glargine versus NPH insulin (9 RCTs): one adult died in the NPH insulin group (Peto OR 0.14, 95% CI 0.00 to 6.98; 8 studies, 2175 participants; moderate-certainty evidence). Four studies with 1013 participants reported QoL showing no true beneficial effect or harmful effect for either intervention (low-certainty evidence). Severe hypoglycaemia was observed in 122/1191 participants (10.2%) in the insulin glargine group compared with 145/1159 participants (12.5%) in the NPH insulin group (RR 0.84, 95% CI 0.67 to 1.04; 9 studies, 2350 participants; moderate-certainty evidence). No participant experienced a NFMI and one participant in the NPH insulin group experienced a NFS in the single study reporting this outcome (585 participants; low-certainty evidence). A total of 109/1131 participants (9.6%) in the insulin glargine group compared with 110/1098 participants (10.0%) in the NPH insulin group experienced SAEs (RR 1.08, 95% CI 0.63 to 1.84; 8 studies, 2229 participants; moderate-certainty evidence). Severe nocturnal hypoglycaemia was observed in 69/938 participants (7.4%) in the insulin glargine group compared with 83/955 participants (8.7%) in the NPH insulin group (RR 0.83, 95% CI 0.62 to 1.12; 6 studies, 1893 participants; moderate-certainty evidence). The MD in HbA1c comparing insulin glargine with NPH insulin was 0.02%, 95% CI -0.1 to 0.1; 9 studies, 2285 participants; moderate-certainty evidence. Insulin detemir versus insulin glargine (2 RCTs),insulin degludec versus insulin detemir (2 RCTs), insulin degludec versus insulin glargine (4 RCTs): there was no evidence of a clinically relevant difference for all main outcomes comparing (ultra-)long-acting insulin analogues with each other. For all outcomes none of the comparisons indicated differences in tests of interaction for children versus adults. AUTHORS' CONCLUSIONS: Comparing insulin detemir with NPH insulin for T1DM showed lower risk of severe hypoglycaemia in favour of insulin detemir (moderate-certainty evidence). However, the 95% prediction interval indicated inconsistency in this finding. Both insulin detemir and insulin glargine compared with NPH insulin did not show benefits or harms for severe nocturnal hypoglycaemia. For all other main outcomes with overall low risk of bias and comparing insulin analogues with each other, there was no true beneficial or harmful effect for any intervention. Data on patient-important outcomes such as QoL, macrovascular and microvascular diabetic complications were sparse or missing. No clinically relevant differences were found between children and adults.

Assessment of basal insulin adherence using 2 methodologies among Texas Medicaid enrollees with type 2 diabetes.

BACKGROUND: Basal insulin is often recommended as the initial therapy for patients with type 2 diabetes who require insulin treatment. Adequate adherence is critical to diabetes management, yet suboptimal insulin adherence has been reported. Second-generation long-acting (SGLA) insulin has higher dosing flexibility and lower hypoglycemia risk and may improve adherence. However, little is known regarding adherence to SGLA insulin and how adherence to SGLA insulin compares with intermediate-acting neutral protamine Hagedorn (NPH) and first-generation long-acting (FGLA) insulin. Measurement of insulin adherence is challenging because of the inaccuracies of recorded days supply of insulin, and traditional medication possession ratio (MPR) may be negatively affected. Adjusted MPR (aMPR) has been developed in an effort to address this issue. OBJECTIVE: To examine the unadjusted and adjusted associations between basal insulin type and adherence to basal insulin using MPR and aMPR. METHODS: This retrospective database study used Texas Medicaid prescription claims from January 1, 2014, through June 30, 2017. The index date was the date of the first basal insulin prescription without the same prescription 6 months before (pre-index), and all patients were followed for 12 months (post-index). Patients aged 18-63 years with ≥ 1 pre-index prescription of an oral hypoglycemia agent (OHA) or a glucagon-like peptide-1 receptor agonist (GLP-1 RA), without any post-index prescription of premixed insulin or a basal insulin different from index insulin, and with continuous enrollment throughout the pre- and post-index periods, were included. The dependent variable was basal insulin adherence over 12 months, measured using MPR and aMPR. Unadjusted and adjusted adherence comparisons were conducted by basal (background) insulin type (NPH, FGLA, and SGLA). Covariates included age, gender, baseline use of basal insulins and comorbid medications, total number of medications, OHA adherence, post-index number of OHAs, and use of bolus insulins and GLP-1 RAs. Analysis of variance, chi-square tests, and multiple logistic regression analyses were performed. RESULTS: Of the 5,034 patients included, NPH, FGLA, and SGLA insulin users accounted for 3.7%, 89.8%, and 6.5%, respectively. The overall mean (SD) age was 50.9 (9.9) years, and 65.9% were female. In the unadjusted bivariate analyses, SGLA insulin users had significantly higher adherence, using either MPR (SGLA 0.68 [0.25] vs. FGLA 0.59 [0.27] vs. NPH 0.55 [0.27]; P < 0.0001) or aMPR (0.83 [0.23] vs. 0.78 [0.26] vs. 0.73 [0.28]; P = 0.0001). After controlling for covariates, insulin type was not significantly associated with the likelihood of being adherent (MPR or aMPR ≥ 0.8) using either measure. CONCLUSIONS: Adherence to SGLA insulin was not different from adherence to other basal insulins after controlling for patient characteristics. Yet, MPR and aMPR have limitations and warrant further confirmation of the study findings. Before new adherence measures for insulin therapy are developed, MPR and aMPR should be used with caution. DISCLOSURES: No specific funding was received for this manuscript. The authors report no potential conflicts of interest. Part of the data from this study was presented as posters at the American Pharmacists Association 2020 Annual Meeting & Exposition, March 20-23, 2020, in National Harbor, MD, and at the International Society for Pharmacoeconomics and Outcomes Research 2020 Conference, May 16-20, 2020, in Orlando, FL.

Using 2nd generation basal insulins in type 2 diabetes: Costs and savings in a comparative economic analysis in Italy, based on the BRIGHT study.

BACKGROUND AND AIMS: To evaluate the economic impact of using 2nd generation basal insulin analogs, Glargine 300 Units/ml (Gla-300) vs Degludec 100 Units/ml (IDeg-100), in patients with type 2 diabetes (T2D). METHODS AND RESULTS: An economic analysis was conducted using findings from the BRIGHT study (the first controlled, head-to-head study comparing Gla-300 vs IDeg-100), and costs for the Italian National Healthcare Service (NHS). A cost-minimization analysis (CMA) and a budget impact analysis (BIA) were conducted. Only pharmacological costs were included in the analysis. The CMA estimated patient treatment costs at 24 weeks and 1 year; the BIA assessed the economic impact of treating the overall Italian population of T2D insulin-naïve patients, who initiated insulin treatment during the period September 2017-August 2018 (N = 55 318). In the BIA, four different scenarios were compared: i) all patients receive IDeg-100 (Scenario A); ii) 61% of patients receive Gla-300, 39% IDeg-100 (Scenario B); iii) 80% of patients receive Gla-300, 20% IDeg-100 (Scenario C); iv) all patients treated with Gla-300 (Scenario D). The average treatment costs per patient were lower with Gla-300 vs IDeg-100 (at 24 weeks: €129 vs €161; at 1 year: €324 vs €409, respectively). Results of the BIA showed that comparing Scenario D vs Scenario A, total savings would amount to €1.76 million at 24 weeks, €4.73 million at 1 year, €5.53 million at 2 years. CONCLUSION: A larger use of Gla-300 vs IDeg-100 for the treatment of T2D patients would lead to a relevant reduction of therapy costs in Italy.

Cost-Effectiveness of Insulin Degludec Versus Insulin Glargine U300 in the Netherlands: Evidence From a Randomised Controlled Trial.

INTRODUCTION: This study aimed to evaluate the short-term cost-effectiveness of insulin degludec 200 units/mL (degludec) versus insulin glargine 300 units/mL (glargine U300) from a Dutch societal perspective. METHODS: A previously published model estimated costs [2018 euros (EUR)] and effectiveness [quality-adjusted life years (QALYs)] with degludec compared with glargine U300 over a 1-year time horizon. The model captured hypoglycaemia rates and insulin dosing. Clinical outcomes were informed by CONCLUDE (NCT03078478), a head-to-head randomised controlled trial in insulin-experienced patients with type 2 diabetes. RESULTS: Treatment with degludec was associated with mean annual cost savings (EUR 24.71 per patient) relative to glargine U300, driven by a lower basal insulin dose and lower severe hypoglycaemia rate with degludec compared with glargine U300. Lower rates of non-severe nocturnal and severe hypoglycaemia resulted in improved effectiveness (+ 0.0045 QALYs) with degludec relative to glargine U300. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes. CONCLUSIONS: This short-term analysis, informed by the latest clinical trial evidence, demonstrated that degludec was a cost-effective treatment option relative to glargine U300. As such, our modelling analysis suggests that degludec would represent an efficient use of Dutch public healthcare resources in this patient population.

Cost-effectiveness of switching to insulin degludec from other basal insulins in real-world clinical practice in Italy.

Aims: The costs associated with insulin therapy and diabetes-related complications represent a significant and growing economic burden for healthcare systems. The aim of this study was to evaluate the cost-effectiveness of switching to insulin degludec (degludec) vs continuing previous basal insulin, in Italian patients with type 1 (T1D) or type 2 (T2D) diabetes, using a long-term economic model.Materials and methods: Data were retrieved from a real-world population of patients from clinical practice in Italy. Clinical parameters included in the base-case model were change from baseline in HbA1c, rates of hypoglycemia, and basal and bolus insulin dose, at 6 months following switch to degludec. Costs of treatments were taken from official Italian pharmaceutical list prices and costs of hypoglycemia were based on the literature. The data were used to populate a long-term (lifetime) IQVIA CORE Diabetes Model to evaluate the incremental cost-effectiveness ratio (ICER) - cost per quality-adjusted life-year (QALY). The robustness of these results was tested with extensive sensitivity analyses by varying the time horizons and abolishing each of the treatment differences and previous basal insulins.Results: The total incremental cost for degludec vs previous basal insulin was €-6,310 and €-2,682 for patients with T1D and T2D, respectively; the switch to degludec resulted in a QALY gain of 0.781 and 0.628. The long-term ICER for degludec vs continuing the previous basal insulin regimen showed that degludec was dominant for both T1D and T2D, meaning that patient health was improved in terms of QALYs with lower healthcare costs. Sensitivity analyses showed that degludec remained dominant in most scenarios including after elimination of any benefit in non-severe hypoglycemia and insulin dose, in both T1D and T2D.Conclusions: Under routine care, switching to degludec is dominant, compared with continuing previous basal insulin, in Italian patients with T1D or T2D.

Evaluation of the Short-Term Cost-Effectiveness of IDegLira Versus Basal Insulin and Basal-Bolus Therapy in Patients with Type 2 Diabetes Based on Attainment of Clinically Relevant Treatment Targets.

BACKGROUND: Effective glycemic control can reduce the risk of complications and their related costs in patients with type 2 diabetes (T2D). Many patients fail to reach hemoglobin A1c (HbA1c) ≤ 6.5% or < 7.0%, often due to adverse effects of treatment, such as hypoglycemia and weight gain. Glycemic targets should be individualized and consider multiple factors, including the risk of adverse events and the patient's characteristics and comorbid conditions. OBJECTIVE: To compare the odds and annual cost of achieving treatment targets, which incorporate HbA1c targets of < 7.5%, < 8.0%, and ≤ 9.0%, with insulin degludec/liraglutide (IDegLira) versus basal insulin and basal-bolus therapy. METHODS: This is a post hoc analysis of the DUAL V and DUAL VII 26-week trials, which randomized patients with T2D uncontrolled (HbA1c 7%-10%) on insulin glargine 100 units/mL (IGlar U100) and metformin to IDegLira or continued IGlar U100 titration (DUAL V) or IGlar U100 + insulin aspart (DUAL VII), all with metformin. Proportions of patients achieving HbA1c targets (< 7.5%, < 8.0%, and ≤ 9.0%) by the end of trial were assessed via 3 outcomes: alone, without either hypoglycemia or weight gain (double composite outcome), or without a combination of hypoglycemia and weight gain (triple composite outcome). The cost per patient achieving the triple composite outcome at each HbA1c target (< 7.5%, < 8.0%, and ≤ 9.0%) was calculated by dividing the annual cost of treatment by the proportion of patients achieving the target. This short-term (1-year) cost-effectiveness analysis was conducted from the perspective of a U.S. health care payer. RESULTS: More patients achieved HbA1c < 7.5% (P < 0.0001) and < 8.0% (P = 0.0003), and a similar percentage achieved HbA1c ≤ 9.0% with IDegLira versus IGlar U100 (DUAL V). Similar proportions of patients achieved all 3 HbA1c targets with IDegLira compared with basal-bolus therapy (DUAL VII). The odds of achieving double or triple composite outcomes were significantly higher for IDegLira versus IGlar U100 or basal-bolus for all 3 HbA1c targets (P < 0.0001 in each case) in both trials. For each $1 spent on IDegLira, the equivalent annual costs per patient to achieve HbA1c targets of < 7.5%, < 8.0%, or ≤ 9.0% without hypoglycemia and without weight gain were $2.43, $2.10, and $2.05, respectively, for IGlar U100 and $6.33, $5.80, and $6.06, respectively, for basal-bolus therapy. CONCLUSIONS: Based on data from DUAL V and DUAL VII, this analysis showed that a greater or similar proportion of patients with T2D reached HbA1c targets with IDegLira compared with IGlar U100/basal-bolus therapy. Odds of achieving double or triple composite outcomes of HbA1c reduction without hypoglycemia and/or without weight gain were greatest for IDegLira. Short-term cost analyses based on the triple composite outcomes suggest that IDegLira is a cost-effective treatment option in the United States compared with either uptitration of IGlar U100 or basal-bolus therapy. DISCLOSURES: This study was supported by Novo Nordisk A/S. The analysis was based on the DUAL V (NCT01952145) and DUAL VII (NCT02420262) trials, which were funded and conducted by Novo Nordisk. This post hoc analysis was conceived and interpreted by the authors and drafted with medical writing support that was funded by Novo Nordisk. Novo Nordisk also reviewed the manuscript for medical accuracy. Hunt and Malkin are employees of Ossian Health Economics and Communications, which received consulting fees from Novo Nordisk during the conduct of this study and has received consulting fees from Novo Nordisk, unrelated to this study. Mocarski, Ranthe, and Schiffman are employees of Novo Nordisk and Novo Nordisk A/S. Cannon has received speaker fees/honoraria from Abbvie, Amgen, and Janssen; speaker fees from Novo Nordisk; and has stock ownership in Novo Nordisk. Bargiota has received speaker fees/honoraria from AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi, Boehringer Ingelheim, and Novartis. Billings has received personal fees from Novo Nordisk, Sanofi, and Dexcom, unrelated to this study. Leiter reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, and GSK, unrelated to this study. Doshi has no relevant conflicts of interest to disclose. Parts of this study were presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Short-term cost-utility of degludec versus glargine U100 for patients with type 2 diabetes at high risk of hypoglycaemia and cardiovascular events: A Canadian setting (DEVOTE 9).

AIMS: To evaluate the short-term cost-effectiveness of insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) from a Canadian public healthcare payer perspective in patients with type 2 diabetes (T2D) who are at high risk of cardiovascular events and hypoglycaemia. MATERIALS AND METHODS: A decision analytic model was developed to estimate costs (2017 Canadian dollars [CAD]) and clinical outcomes (quality-adjusted life years [QALYs]) with degludec vs glargine U100 over a 2-year time horizon. The model captured first major adverse cardiovascular event, death, severe hypoglycaemia and insulin dosing. Clinical outcomes were informed by a post hoc subgroup analysis of the DEVOTE trial (NCT01959529), which compared the cardiovascular safety of degludec and glargine U100 in patients with T2D who are at high cardiovascular risk. High hypoglycaemia risk was defined as the top quartile of patients (n = 1887) based on an index of baseline hypoglycaemia risk factors. RESULTS: In patients at high hypoglycaemia risk, degludec was associated with mean cost savings (CAD 129 per patient) relative to glargine U100, driven by a lower incidence of non-fatal myocardial infarction, non-fatal stroke and severe hypoglycaemia, which offset the slightly higher cost of treatment with degludec. A reduced risk of cardiovascular death and severe hypoglycaemia resulted in improved effectiveness (+0.0132 QALYs) with degludec relative to glargine U100. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes. CONCLUSION: Over a 2-year period, degludec improved clinical outcomes at a lower cost as compared to glargine U100 in patients with T2D at high risk of cardiovascular events and hypoglycaemia.

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.

Switching basal insulins in type 2 diabetes: practical recommendations for health care providers.

Basal insulin remains the mainstay of treatment of type 2 diabetes when diet changes and exercise in combination with oral drugs and other injectable agents are not sufficient to control hyperglycemia. Insulin therapy should be individualized, and several factors influence the choice of basal insulin; these include pharmacological properties, patient preferences, and lifestyle, as well as health insurance plan formularies. The recent availability of basal insulin formulations with longer durations of action has provided further dosing flexibility; however, patients may need to switch agents throughout therapy for a variety of personal, clinical, or economic reasons. Although a unit-to-unit switching approach is usually recommended, this conversion strategy may not be appropriate for all patients and types of insulin. Glycemic control and risk of hypoglycemia must be closely monitored by health care providers during the switching process. In addition, individual changes in care and formulary coverage need to be adequately addressed in order to enable a smooth transition with optimal outcomes.

Evaluation of the long-term cost-effectiveness of IDegLira versus liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the USA.

BACKGROUND AND AIMS: IDegLira, a fixed ratio combination of insulin degludec and glucagon-like peptide-1 receptor agonist liraglutide, utilizes the complementary mechanisms of action of these two agents to improve glycemic control with low risk of hypoglycemia and avoidance of weight gain. The aim of the present analysis was to assess the long-term cost-effectiveness of IDegLira vs liraglutide added to basal insulin, for patients with type 2 diabetes not achieving glycemic control on basal insulin in the US setting. METHODS: Projections of lifetime costs and clinical outcomes were made using the IMS CORE Diabetes Model. Treatment effect data for patients receiving IDegLira and liraglutide added to basal insulin were modeled based on the outcomes of a published indirect comparison, as no head-to-head clinical trial data is currently available. Costs were accounted in 2015 US dollars ($) from a healthcare payer perspective. RESULTS: IDegLira was associated with small improvements in quality-adjusted life expectancy compared with liraglutide added to basal insulin (8.94 vs 8.91 discounted quality-adjusted life years [QALYs]). The key driver of improved clinical outcomes was the greater reduction in glycated hemoglobin associated with IDegLira. IDegLira was associated with mean costs savings of $17,687 over patient lifetimes vs liraglutide added to basal insulin, resulting from lower treatment costs and cost savings as a result of complications avoided. CONCLUSIONS: The present long-term modeling analysis found that IDegLira was dominant vs liraglutide added to basal insulin for patients with type 2 diabetes failing to achieve glycemic control on basal insulin in the US, improving clinical outcomes and reducing direct costs.

Severe hypoglycaemia in adults with insulin-treated diabetes: impact on healthcare resources.

AIMS: To assess resource utilization associated with severe hypoglycaemia across three insulin regimens in a large phase 3a clinical programme involving people with Type 1 diabetes treated with basal-bolus insulin, people with Type 2 diabetes treated with multiple daily injections and people with Type 2 diabetes treated with basal-oral therapy. METHODS: Data relating to severe hypoglycaemia events (defined as episodes requiring external assistance) from the insulin degludec and insulin degludec/insulin aspart programme (15 trials) were analysed using descriptive statistics. Comparators included insulin glargine, biphasic insulin aspart, insulin detemir and sitagliptin. Mealtime insulin aspart was used in some regimens. This analysis used the serious adverse events records, which documented the use of ambulance/emergency teams, a hospital/emergency room visit ≤ 24 h, or a hospital visit > 24 h. RESULTS: In total, 536 severe hypoglycaemia events were analysed, of which 157 (29.3%) involved an ambulance/emergency team, 64 (11.9%) led to hospital/emergency room attendance of ≤ 24 h and 36 (6.7%) required hospital admission (> 24 h). Although there were fewer events in people with Type 2 diabetes compared with Type 1 diabetes, once a severe episode occurred, the tendency to utilize healthcare resources was higher in Type 2 diabetes vs. Type 1 diabetes. A higher proportion (47.6%) in the basal-oral therapy group required hospital treatment for > 24 h versus the Type 1 diabetes (5.0%) and Type 2 diabetes multiple daily injections (5.3%) groups. CONCLUSION: This analysis suggests that severe hypoglycaemia events often result in emergency/ambulance calls and hospital treatment, incurring a substantial health economic burden, and were associated with all insulin regimens.

[POET2 registry: Comparison of annual direct medical costs of treating type 2 diabetes after addition of insulin NPH or insulin glargine to oral antidiabetic therapy in the Czech Republic]. / Registr POET2: srovnání prímých rocních zdravotnických nákladu na lécbu diabetu 2. typu po zahájení lécby inzulinem NPH nebo inzulinem glargin v kombinaci s perorálními antidiabetiky v Ceské republice.

INTRODUCTION: Poor glycemic control and the resulting development of complications of type 2 diabetes (DM2T) increase treatment costs. If adequate glycemic control cannot be achieved by lifestyle modifications and oral antidiabetic (OAD) therapy, initiation of insulin therapy is recommended. Cost effectiveness of basal insulins of the type NPH or glargine in combination with OAD for the treatment of DM2T was examined in a number of pharmacoeconomic studies. However, none of these studies were conducted in the Czech Republic. Therefore, the aim of the project POET2 was to compare annual direct medical costs of treating DM2T after addition of insulin NPH or glargine to OAD therapy in a clinical practice setting in the Czech Republic. METHODOLOGY: Data collected from 1967 patients who met the criteria for inclusion into the non-interventional prospective registry POET2 (DM2T, ongoing OAD therapy, glycated hemoglobin HbA1c > 6 % IFCC) and who were observed for 12 months following the start of insulin therapy (glargine: n = 1061 vs NPH: n = 906) were analysed. Costs of treatment were analysed from the perspective of health insurance companies and included costs of medication, medical devices and medical procedures. RESULTS: In both treatment groups a reduction of HbA1c (glargine group: by 1.77 % IFCC vs NPH group: by 1.73 % IFCC) and fasting plasma glucose (glargine group: by 3.67 mmol/l vs NPH group: by 3.63 mmol/l) was observed. Insulin glargine therapy was associated with the incidence of a significantly lower number of documented symptomatic hypoglycemic events (glargine group: 0.840 events per patient and year of treatment vs. NPH group: 1.053 events per patient and year of treatment; p < 0.05). Overall annual direct medical costs associated with the initiation of basal insulin treatment were higher on average by 2547.07 CZK among patients treated with insulin glargine (glargine group: 12173.09 ± 4169.44 CZK vs NPH group: 9626.02 ± 3432.79 CZK; p < 0.001) due to higher costs of medication (glargine group: 7992.97 ± 4001.81 CZK vs NPH group: 3784.2 ± 3181.48 CZK; p < 0.001). By contrast, costs of medical devices (glargine group: 2332.08 ± 917.84 CZK vs NPH group: 3893.95 ± 989.79 CZK; p < 0.001) and medical procedures (glargine group: 1848.04 ± 684.89 CZK vs NPH group: 1947.87 ± 685.43 CZK; p < 0.001) were lower among patients treated with insulin glargine. CONCLUSION: Addition of basal insulin to OAD therapy was an efficacious therapeutic intervention for the treatment of DM2T in a clinical practice setting in the Czech Republic. Overall annual direct medical costs were higher among patients treated with insulin glargine than among patients treated with insulin NPH. However, costs of medical devices and medical procedures were lower in the insulin glargine group. In addition, incidence of hypoglycemia was significantly lower among patients treated with insulin glargine.

A cost comparison of long-acting insulin analogs vs NPH insulin-based treatment in patients with type 2 diabetes using routinely collected primary care data from the UK.

AIM: The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs. METHODS: Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models. RESULTS: A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant. CONCLUSIONS: Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.

Insulin glargine in a Brazilian state: should the government disinvest? An assessment based on a systematic review.

INTRODUCTION AND OBJECTIVE: The costs of the insulin analogue (insulin glargine) have been growing appreciably in the State of Minas Gerais in Brazil, averaging 291% per year in recent years. This growth has been driven by an increasing number of successful law suits and a 536% price difference between insulin glargine and neutral protamine Hagedorn (NPH) insulin. One potential way to address this is to undertake a systematic review assessing the efficacy and safety of insulin glargine analogue compared with NPH insulin in patients with type 1 diabetes mellitus (T1DM), and, as a result, provide published data to support future recommended activities by the State of Minas Gerais. These could include maintaining it on the list of the Public Health System (SUS) provided there is a price reduction. Alternatively, the review could provide potential arguments to defend against future law suits should the authorities decide to delist insulin glargine. METHODS: A systematic review of published studies researching the effectiveness of insulin glargine in patients with T1DM between January 1970 and July 2009 in MEDLINE (PubMed), the Latin American and Caribbean Centre on Health Sciences Information, the Cochrane Controlled Trials Databases and the National Health Service Centre for Reviews and Dissemination. Inclusion criteria included insulin glargine on its own or combined with other insulin formulations. Only randomised controlled clinical trials were included. Initially, the titles of all studies were assessed by two independent reviewers before being potentially discarded, with the quality of papers assessed using a modified Jadad scale. The outcome measures included blood levels of glycated haemoglobin, episodes of hypoglycaemia, adverse effects and the reduction of microvascular and macrovascular end-organ complications of T1DM. RESULTS: Out of 803 studies found in the selected databases, only eight trials met the inclusion criteria. Most of the studies were of poor methodological quality or had a high risk of bias, with a mean score of 2.125 on the Jadad scale. No study could be classified as double-blind, and only one study documented the increased efficacy of insulin glargine in relation to both glycaemic control and hypoglycaemic episodes. Typically, there was no significant difference between insulin glargine and NPH insulins. CONCLUSIONS: This systematic review showed no therapeutic benefit of insulin glargine over other insulin formulations studied when analysing together glycaemic control and the frequency and severity of hypoglycaemia. We therefore recommend to the State Authority to delist insulin glargine or renegotiate a price reduction with the manufacturer. This systematic review provides support for this decision as well as documentation to combat potential law suits if discussions are unsatisfactory.

Cost-effectiveness of insulin degludec compared with insulin glargine for patients with type 2 diabetes treated with basal insulin - from the UK health care cost perspective.

AIMS: The aim of this analysis was to evaluate the cost-effectiveness of insulin degludec (IDeg) versus insulin glargine (IGlar) in adults with type 2 diabetes mellitus (T2DM) who are considered appropriate for treatment with a basal insulin analogue, using a short-term economic model. METHODS: Meta-analysis data from three phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg versus IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. RESULTS: IDeg is a cost-effective treatment option versus IGlar in patients with T2DM using basal insulin. Base case incremental cost-effectiveness ratios (ICERs) were estimated at £15,795 per quality-adjusted life-year (QALY) and £13,078 per QALY, which are below commonly accepted thresholds for cost-effectiveness. Sensitivity analyses demonstrated that hypoglycaemia event rates had an important effect on the results. With higher event rates for non-severe hypoglycaemia IDeg was less costly and more effective than IGlar (dominant). Conversely, using lower event rates for severe hypoglycaemia generated higher ICERs. Using hypoglycaemia rates from a subgroup of patients who experienced ≥1 hypoglycaemic event per year IDeg was highly cost-effective versus IGlar; with estimated ICERS of £4887 and £2625 per QALY. CONCLUSIONS: This short-term modelling approach allows the economic evaluation of newer insulin analogues when advanced long-term modelling based on HbA1c differences is inappropriate. For patients with T2DM who are considered appropriate for treatment with a basal insulin analogue, IDeg is a cost-effective treatment option compared with IGlar and offers additional benefits to subgroups of patients, such as those suffering from recurrent hypoglycaemia.

Safety, effectiveness, and cost of long-acting versus intermediate-acting insulin for type 1 diabetes: protocol for a systematic review and network meta-analysis.

BACKGROUND: Type 1 diabetes mellitus (T1DM) causes progressive destruction of pancreatic beta cells leading to absolute insulin deficiency. Treatment of T1DM requires insulin, and some evidence suggests that longer acting insulin analogues might have a higher effectiveness and greater safety profile compared to intermediate-acting insulin. Our objective is to evaluate the comparative effectiveness, safety, and cost of long-acting insulin versus intermediate-acting insulin through a systematic review and network meta-analysis. DESIGN/METHODS: Studies examining long-acting versus intermediate-acting insulin or placebo preparations for adult T1DM patients will be included. The primary outcome is glycosylated hemoglobin (A1C), and secondary outcomes include emergency department and physician visits, hospital admissions, weight gain, quality of life, microvascular complications (e.g., retinopathy), macrovascular complications (e.g., cardiovascular disease), all-cause mortality, incident cancers, and cost. We will include experimental [randomized clinical trials (RCTs), quasi-RCTs, non-RCTs], quasi-experimental (controlled before-after, interrupted time series), observational (cohort), and cost studies, of any duration of follow-up, conducted during all time periods, and disseminated in any language.We will conduct comprehensive searches of electronic databases from inception onwards, including MEDLINE, Cochrane Central Register of Controlled Trials, and EMBASE. We will also search for difficult to locate and unpublished literature by searching dissertation databases, public health organization websites, and trial registries. After a calibration exercise using our eligibility criteria and data abstraction forms, two reviewers will screen all citations, full-text articles, and abstract data in duplicate. Conflicts will be resolved by team discussion. Using a similar process, the Cochrane Effective Practice and Organization of Care Risk of Bias tool will be used to appraise the risk of bias of experimental and quasi-experimental studies, while the Newcastle Ottawa Scale will be used to assess the methodological quality of cohort studies. If feasible and appropriate, we will conduct a random effects meta-analysis, as well as a network meta-analysis. DISCUSSION: Our systematic review will be of utility to healthcare providers, policy-makers, T1DM patients and family members regarding treatment options of long-acting versus intermediate-acting insulin preparations. TRIAL REGISTRATION: PROSPERO registry number: CRD42013003610.

A real-world study of patients with type 2 diabetes initiating basal insulins via disposable pens.

INTRODUCTION: Real-world data comparing outcomes of type 2 diabetes mellitus (T2DM) patients initiating different insulin regimens can help with treatment decisions and patient management. Clinical and economic outcomes following initiation with insulin glargine disposable pen (GLA-P) or insulin detemir disposable pen (DET-P) in T2DM patients were compared over 1-year follow-up. METHODS: This retrospective cohort analysis was conducted on data in a US national managed care claims database (July 2006 to September 2010) from patients initiating insulin treatment with GLA-P or DET-P. Treatment persistence, adherence, glycated hemoglobin (A1C), hypoglycemic events, and healthcare costs during follow-up were compared. RESULTS: In all, 1682 patients were identified; 1016 (60.4%) started using GLA-P, 666 (39.6%) started using DET-P. After 1:1 propensity score matching, each cohort comprised 640 patients. Patients initiating GLA-P were significantly more likely to persist and adhere to treatment, and used a lower daily consumption dose. Over the last quarter of follow-up, fewer GLA-P users switched to DET-P compared with those switching from DET-P to GLA-P. GLA-P was associated with lower A1C levels and higher reduction of A1C levels from baseline, with no significant difference in the number of patients having hypoglycemic events. Patients in both cohorts had similar total and diabetes-related healthcare costs, but healthcare costs were lower in the GLA-P cohort for each 1% reduction in A1C from baseline. CONCLUSION: This real-world study demonstrates that patients initiating GLA-P were more likely to persist with and adhere to treatment, with better glycemic control and similar overall hypoglycemia rate at no increase in healthcare cost.