Dataset Information

Cost-effectiveness of long-acting insulin analogues vs intermediate/long-acting human insulin for type 1 diabetes: A population-based cohort followed over 10 years.

ABSTRACT:

Aims

This study assessed the cost-effectiveness of long-acting insulin analogues (LAIAs) vs intermediate/long-acting human insulin (ILAHI) for patients with type 1 diabetes (T1D) in real-world clinical practice.

Methods

Individual-level analyses were conducted within a longitudinal population-based cohort of 540 propensity score-matched T1D patients (LAIAs, n = 270; ILAHI, n = 270) with over 10 years of follow-up using Taiwan's National Health Insurance Research Database, 2004-2013, from third-party payer and healthcare sector perspectives. The study outcomes included the number needed to treat (NNT) to prevent one case of clinical events (eg, hypoglycaemia, diabetes-related complications), medical costs, and cost per case of events prevented. Cost estimates are presented in 2013 British pounds (GBP, £).

Results

The NNTs using LAIAs vs ILAHI to avoid one case of hypoglycaemia requiring medical assistance, outpatient hypoglycaemia and any diabetes-related complications were 12, 9 and 10 for mean follow-up periods of 5.84, 6.02 and 3.62 years, respectively. From third-party payer and healthcare sector perspectives, using LAIAs instead of ILAHI saved GBP6924-GBP7116 per case of hypoglycaemia requiring medical assistance prevented, GBP5346-GBP5508 per case of outpatient hypoglycaemia prevented, and GBP3570-GBP3680 per case of any diabetes-related complications prevented. Sensitivity analyses considering sampling uncertainty showed that using LAIAs over ILAHI yields at least a 76% probability of cost-saving for avoiding one case of hypoglycaemia requiring medical assistance, outpatient hypoglycaemia or any diabetes-related complications.

Conclusions

This real-world evidence reveals that compared with ILAHI, the greater pharmaceutical costs associated with LAIAs for patients with T1D could be substantially offset by savings from averted hypoglycaemia or diabetes-related complications.

SUBMITTER: Lee TY

PROVIDER: S-EPMC7163379 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportanceCardiovascular events and mortality are the principal causes of excess mortality and health care costs for people with type 2 diabetes. No large studies have specifically compared long-acting insulin alone with long-acting plus short-acting insulin with regard to cardiovascular outcomes.ObjectiveTo compare cardiovascular events and mortality in adults with type 2 diabetes receiving long-acting insulin who do or do not add short-acting insulin.Design, setting, and participantsThis retrospective cohort study emulated a randomized experiment in which adults with type 2 diabetes who experienced a qualifying glycated hemoglobin A1c (HbA1c) level of 6.8% to 8.5% with long-acting insulin were randomized to continuing treatment with long-acting insulin (LA group) or adding short-acting insulin within 1 year of the qualifying HbA1c level (LA plus SA group). Retrospective data in 4 integrated health care delivery systems from the Health Care Systems Research Network from January 1, 2005, to December 31, 2013, were used. Analysis used inverse probability weighting estimation with Super Learner for propensity score estimation. Analyses took place from April 1, 2018, to June 30, 2019.ExposuresLong-acting insulin alone or with added short-acting insulin within 1 year from the qualifying HbA1c level.Main outcomes and measuresMortality, cardiovascular mortality, acute myocardial infarction, stroke, and hospitalization for heart failure.ResultsAmong 57 278 individuals (39 279 with data on cardiovascular mortality) with a mean (SD) age of 60.6 (11.5) years, 53.6% men, 43.5% non-Hispanic White individuals, and 4 years of follow-up (median follow-up of 11 [interquartile range, 5-20] calendar quarters), the LA plus SA group was associated with increased all-cause mortality compared with the LA group (hazard ratio, 1.27; 95% CI, 1.05-1.49) and a decreased risk of acute myocardial infarction (hazard ratio, 0.89; 95% CI, 0.81-0.97). Treatment with long-acting plus short-acting insulin was not associated with increased risks of congestive heart failure, stroke, or cardiovascular mortality.Conclusions and relevanceFindings of this retrospective cohort study suggested an increased risk of all-cause mortality and a decreased risk of acute myocardial infarction for the LA plus SA group compared with the LA group. Given the lack of an increase in major cardiovascular events or cardiovascular mortality, the increased all-cause mortality with long-acting plus short-acting insulin may be explained by noncardiovascular events or unmeasured confounding.

Project description:ObjectiveTo examine the safety, effectiveness, and cost effectiveness of long acting insulin for type 1 diabetes.DesignSystematic review and network meta-analysis.Data sourcesMedline, Cochrane Central Register of Controlled Trials, Embase, and grey literature were searched through January 2013.Study selectionRandomized controlled trials or non-randomized studies of long acting (glargine, detemir) and intermediate acting (neutral protamine Hagedorn (NPH), lente) insulin for adults with type 1 diabetes were included.Results39 studies (27 randomized controlled trials including 7496 patients) were included after screening of 6501 titles/abstracts and 190 full text articles. Glargine once daily, detemir once daily, and detemir once/twice daily significantly reduced hemoglobin A1c compared with NPH once daily in network meta-analysis (26 randomized controlled trials, mean difference -0.39%, 95% confidence interval -0.59% to -0.19%; -0.26%, -0.48% to -0.03%; and -0.36%, -0.65% to -0.08%; respectively). Differences in network meta-analysis were observed between long acting and intermediate acting insulin for severe hypoglycemia (16 randomized controlled trials; detemir once/twice daily versus NPH once/twice daily: odds ratio 0.62, 95% confidence interval 0.42 to 0.91) and weight gain (13 randomized controlled trials; detemir once daily versus NPH once/twice daily: mean difference 4.04 kg, 3.06 to 5.02 kg; detemir once/twice daily versus NPH once daily: -5.51 kg, -6.56 to -4.46 kg; glargine once daily versus NPH once daily: -5.14 kg, -6.07 to -4.21). Compared with NPH, detemir was less costly and more effective in 3/14 cost effectiveness analyses and glargine was less costly and more effective in 2/8 cost effectiveness analyses. The remaining cost effectiveness analyses found that detemir and glargine were more costly but more effective than NPH. Glargine was not cost effective compared with detemir in 2/2 cost effectiveness analyses.ConclusionsLong acting insulin analogs are probably superior to intermediate acting insulin analogs, although the difference is small for hemoglobin A1c. Patients and their physicians should tailor their choice of insulin according to preference, cost, and accessibility.Systematic review registrationPROSPERO CRD42013003610.

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Project description:The effects of insulin on cardiomyocytes, such as positive inotropic action and glucose uptake are well described. However, in vitro studies comparing long-acting insulin analogues with regard to cardiomyocyte signalling and function have not been systematically conducted.Insulin receptor (IR) binding was assessed using membrane embedded and solubilised IR preparations. Insulin signalling was analysed in adult rat ventricular myocytes (ARVM) and HL-1 cardiac cells. Inotropic effects were examined in ARVM and the contribution of Akt to this effect was assessed by specific inhibition with triciribine. Furthermore, beating-rate in Cor.4U(®) human cardiomyocytes, glucose uptake in HL-1 cells, and prevention from H2O2 induced caspase 3/7 activation in cardiac cells overexpressing the human insulin receptor (H9c2-E2) were analysed. One-way ANOVA was performed to determine significance between conditions.Insulin degludec showed significant lower IR affinity in membrane embedded IR preparations. In HL-1 cardiomyocytes, stimulation with insulin degludec resulted in a lower Akt(Ser(473)) and Akt(Thr(308)) phosphorylation compared to insulin, insulin glargine and its active metabolite M1 after 5- and 10-min incubation. After 60-min treatment, phosphorylation of Akt was comparable for all insulin analogues. Stimulation of glucose uptake in HL-1 cells was increased by 40-60 %, with a similar result for all analogues. Incubation of electrically paced ARVM resulted for all insulins in a significantly increased sarcomere shortening, contractility- and relaxation-velocity. This positive inotropic effect of all insulins was Akt dependent. Additionally, in Cor.4U(®) cardiomyocytes a 10-20 % increased beating-rate was detected for all insulins, with slower onset of action in cells treated with insulin degludec. H9c2-E2 cells challenged with H2O2 showed a fivefold increase in caspase 3/7 activation, which could be abrogated by all insulins used.In conclusion, we compared for the first time the signalling and functional impact of the long-acting insulin analogues insulin glargine and insulin degludec in cardiomyocyte cell models. We demonstrated similar efficacy under steady-state conditions relative to regular insulin in functional endpoint experiments. However, it remains to be shown how these results translate to the in vivo situation.

Project description:BACKGROUND: Insulin analogues may be associated with fewer episodes of hypoglycemia than conventional insulins. However, they are costly alternatives. We compared the cost-effectiveness of insulin analogues and conventional insulins used to treat type 1 and type 2 diabetes mellitus in adults. METHODS: We conducted a cost-effectiveness evaluation of insulin analogues versus conventional insulins using the Center for Outcomes Research Diabetes Model. We compared rapid-acting analogues (insulin aspart and insulin lispro) with regular human insulin, and long-acting analogues (insulin glargine and insulin detemir) with neutral protamine Hagedorn insulin. We derived clinical information for the comparisons from meta-analyses of randomized controlled trials. We obtained cost and utility estimates from published sources. We performed sensitivity analyses to test the robustness of our results. RESULTS: For type 1 diabetes, insulin aspart was more effective and less costly than regular human insulin. Insulin lispro was associated with an incremental cost of Can$28,996 per quality-adjusted life-year. The incremental cost per quality-adjusted life-year was Can$87,932 for insulin glargine and Can$387,729 for insulin detemir, compared with neutral protamine Hagedorn insulin. For type 2 diabetes, insulin aspart was associated with an incremental cost of Can$22,488 per quality-adjusted life-year compared with regular human insulin. For insulin lispro, the incremental cost was Can$130,865. Compared with neutral protamine Hagedorn insulin, insulin detemir was less effective and more costly. Insulin glargine was associated with an incremental cost of Can$642,994 per quality-adjusted life-year. The model was sensitive to changes in the effect size of hemoglobin A(1c) and to decrements applied to utility scores when fear of hypoglycemia was included as a factor. INTERPRETATION: The cost-effectiveness of insulin analogues depends on the type of insulin analogue and whether the patient receiving the treatment has type 1 or type 2 diabetes. With the exception of rapid-acting insulin analogues in type 1 diabetes, routine use of insulin analogues, especially long-acting analogues in type 2 diabetes, is unlikely to represent an efficient use of finite health care resources.