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Aims: To compare SGLT2 inhibitors and GLP-1 agonists on cardiovascular (CV) outcomes, treatment persistence/discontinuation, healthcare utilization and costs., Methods: This retrospective cohort study utilized medical and pharmacy claims to identify new SGLT2 inhibitor or GLP-1 agonist users from January 2015 to June 2017. A total of 5,507 patients were included in each treatment group after 1:1 propensity score matching. Cox proportional hazards models were used to compare CV outcomes and treatment discontinuation. Healthcare utilization and costs were compared using Wilcoxon signed rank test., Results: No differences in the primary composite CV outcome or secondary CV outcome were observed. Patients using GLP-1 agonists were more likely to discontinue treatment (hazard ratio 1.15, 95% confidence interval 1.10-1.21) and more likely to have an inpatient hospitalization (14.4% vs. 11.9%, P < 0.001) or emergency department visit (27.4% vs. 23.5%, P < 0.001) compared to patients on SGLT2 inhibitors. The average per-person per-month cost difference was +$179 for total cost (P < 0.001), +$70 for medical cost (P < 0.001) and +$108 for pharmacy cost (P < 0.001) for GLP-1 agonists compared to SGLT2 inhibitors., Conclusions: Differences in composite CV outcomes were not established. However, other findings that favored SGLT2 inhibitors should be weighed against the known risks associated with this therapeutic class., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective To compare the cost-utility of the glucagon-like peptide-1 receptor agonist albiglutide with those of insulin lispro (both in combination with insulin glargine), insulin glargine, and the dipeptidyl peptidase-4 inhibitor sitagliptin, representing treatments along the type 2 diabetes treatment continuum. Methods The Centre for Outcomes Research and Effectiveness (CORE) Diabetes Model was used for the cost-utility analysis. Data from three Phase 3 clinical trials (HARMONY 6, HARMONY 4, and HARMONY 3) evaluating albiglutide for the treatment of patients with type 2 diabetes were used for the baseline characteristics and treatment effects. Utilities and costs were derived from published sources. Results Albiglutide treatment was associated with an improvement in mean quality-adjusted life expectancy of 0.099, 0.033, and 0.101 years when compared with insulin lispro, insulin glargine, and sitagliptin, respectively. Over the 50-year time horizon, mean total costs in the albiglutide arm were $4332, $2597, and $2223 more than in the other respective treatments. These costs resulted in an incremental cost-utility ratio of $43,541, $79,166, and $22,094 per quality-adjusted life-year (QALY) gained for albiglutide vs insulin lispro, insulin glargine, and sitagliptin, respectively. At a willingness-to-pay threshold of $50,000 per QALY gained, there was a 53.0%, 41.5%, and 67.5% probability of albiglutide being cost-effective compared with the other respective treatments. Limitations This analysis was an extrapolation over a 50-year time horizon based on relatively short-term data obtained during clinical trials. It does not take into account potential differences between the respective treatments in adherence and persistence that can influence both effects and costs. Conclusions Albiglutide represents a reasonable treatment option for patients with type 2 diabetes based on its cost-utility, relative to insulin lispro, insulin glargine, and sitagliptin.

Background: As novel treatments for type II diabetes enter the market, there is a need to assess their long-term clinical and economic outcomes against currently available treatment alternatives. Objective compilation and evaluation of current pharmacoeconomic evidence can assist payers and decision makers in determining the appropriate place in therapy of a new medication., Objective: Our objective was to review the existing pharmacoeconomic literature evaluating the cost effectiveness and overall costs of treatment associated with liraglutide in type II diabetes., Data Sources: Medical literature indexed in MEDLINE, EMBASE, PsycINFO, CINAHL, and EconLit through 1 June 2014 was searched., Study Selection: Full-text, English-language cost-effectiveness, cost-utility, and other cost analyses in type II diabetes that compared liraglutide to one or more anti-diabetic agents were included. Initial screening was based on relevance of titles and abstracts followed by examination of the study methods of each remaining manuscript. Studies conducting original pharmacoeconomic analyses were chosen for inclusion., Study Appraisal Methods: Articles meeting the inclusion criteria were retrieved, and information on the study design and results was abstracted. Abstracted data elements were chosen and assessed based on the authors' experience as well as criteria set forth by the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) Health Economic Evaluation Publication Guidelines Task Force. Additionally, reported incremental cost-effectiveness ratios (ICERs) and selected sensitivity analysis results were converted to $US, year 2012 values, in order to facilitate comparison across studies., Results: A total of six cost studies and seven cost-utility studies were identified for inclusion. Across cost studies, liraglutide treatment resulted in costs ranging from a loss of $US2,730 (liraglutide 1.8 mg vs. sitagliptin; pharmacy costs only) over a 1-year time horizon to a savings of $US9,367 (liraglutide 1.8 mg vs. glimepiride; diabetes-related complication costs only) over a 30-year time horizon. Cost-utility analysis results reported base-case ICERs ranging from $US15,774 (vs. glimepiride) to $US40,128 (vs. rosiglitazone) per quality-adjusted life-year (QALY) ($US, year 2012) for liraglutide 1.2 mg and $US8,497 (vs. exenatide) to $US66,031 (vs. rosiglitazone)/QALY ($US, year 2012) for liraglutide 1.8 mg. Estimates were most sensitive to variations in time horizon and cardiovascular complication rates. Based on frequently cited, country-specific cost-utility thresholds, liraglutide was determined to have a probability of being cost effective of between 58 % (liraglutide 1.8 mg vs. sitagliptin) and 93 % (liraglutide 1.2 mg vs. glimepiride)., Limitations: Weaknesses of included studies related primarily to study model inputs that assumed long-term morbidity and mortality benefits in favor of liraglutide based on improvements in clinical biomarkers observed in short-term clinical trials. The exclusion of drug acquisition costs in two identified cost studies as well as the assumed lifetime duration of treatment with liraglutide in several cost-utility studies were also identified as weaknesses. The authors' review was limited by the possibility of incomplete literature retrieval, unintended omission of relevant data elements, and comparison of costs and ICERs generated from healthcare systems from differing countries., Conclusions: The current literature presents liraglutide as a cost-effective adjunct treatment for type II diabetes that may also be associated with a reduction in diabetes-related complication costs; however, ICER values are largely dependent on assumptions regarding the benefits of long-term liraglutide treatment and the time horizon of the analysis. Real-world use may make liraglutide unattractive from a payer and policy-maker perspective.

Background: To evaluate the long-term cost-effectiveness of liraglutide versus sitagliptin or exenatide, added to oral antidiabetic drug mono- or combination therapy respectively, in patients with Type 2 diabetes in Greece., Methods: The CORE Diabetes Model, a validated computer simulation model, was adapted to the Greek healthcare setting. Patient and intervention effects data were gathered from a clinical trial comparing liraglutide 1.2 mg once daily vs. sitagliptin 100 mg once daily, both combined with metformin, and a clinical trial comparing liraglutide 1.8 mg once daily vs. exenatide 10 μg twice daily, both as add-on to metformin, glimepiride or both. Direct costs were reported in 2013 Euros and calculated based on published and local sources. All future outcomes were discounted at 3.5% per annum, and the analysis was conducted from the perspective of a third-party payer in Greece., Results: Over a patient's lifetime, treatment with liraglutide 1.2 mg vs. sitagliptin drove a mean increase in discounted life expectancy of 0.13 (SD 0.23) years and in discounted quality-adjusted life expectancy of 0.19 (0.16) quality-adjusted life years (QALYs), whereas therapy with liraglutide 1.8 mg vs. exenatide yielded increases of 0.14 (0.23) years and 0.19 (0.16) QALYs respectively. As regards lifetime direct costs, liraglutide 1.2 mg resulted in greater costs of €2797 (€1468) versus sitagliptin, and so did liraglutide 1.8 mg compared with exenatide (€1302 [€1492]). Liraglutide 1.2 and 1.8 mg doses were associated with incremental cost effectiveness ratios of €15101 and €6818 per QALY gained, respectively., Conclusions: Liraglutide is likely to be a cost-effective option for the treatment of Type 2 diabetes in a Greek setting.

Objective: To evaluate long-run cost-effectiveness in a Swedish setting for liraglutide compared with sulphonylureas (glimepiride) or sitagliptin, all as add-on to metformin for patients with type 2 diabetes insufficiently controlled with metformin in monotherapy., Methods: The IHE Cohort Model of Type 2 Diabetes was used to evaluate clinical and economic outcomes from a societal perspective. Model input data were obtained from two clinical trials, the Swedish National Diabetes Register and the literature. Cost data reflected year 2013 price level. The robustness of results was checked with one-way-sensitivity analysis and probability sensitivity analysis., Results: The cost per QALY gained for liraglutide (1.2 mg) compared to SU (glimepiride 4 mg), both as add-on to metformin, ranged from SEK 226,000 to SEK 255,000 in analyzed patient cohorts. The cost per QALY for liraglutide (1.2 mg) vs sitagliptin (100 mg) as second-line treatment was lower, ranging from SEK 149,000 to SEK 161,000. Costs of preventive treatment were driving costs, but there was also a cost offset from reduced costs of complications of ∼ 20%. Notable cost differences were found for nephropathy, stroke, and heart failure. The predicted life expectancy with liraglutide increased the cost of net consumption for liraglutide., Limitations: The analysis was an ex-ante analysis using model input data from clinical trials which may not reflect effectiveness in real-world clinical practice in broader patient populations. This limitation was explored in the sensitivity analysis. The lack of specific data on loss of production due to diabetes complications implied that these costs may be under-estimated., Conclusions: Treatment strategies with liraglutide 1.2 mg improved the expected quality-of-life and increased costs when compared to SU and to sitagliptin for second-line add-on treatments. The cost per QALY for liraglutide was in the range considered medium by Swedish authorities.

In the current context of limited economic and health resources, efficiency of drug treatments is of paramount importance, and their clinical effects and related direct costs should therefore be analyzed. Liraglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist approved for the treatment of type 2 diabetes mellitus (T2DM) which, in addition to its normoglycemic effects, induces a significant improvement in body weight and several cardiovascular risk factors. The aim of this narrative review is to summarize the available evidence about the effects of liraglutide upon cardiovascular risk factors and how these improve its cost-effectiveness profile. Despite the relatively higher cost of liraglutide as compared to other alternative therapies, liraglutide has been shown to be cost-effective when clinical indicators and total costs associated to T2DM management are analyzed., (Copyright © 2013 SEEN. Published by Elsevier Espana. All rights reserved.)

Introduction: While the liraglutide effect and action in diabetes (LEAD-6) clinical trial compared the efficacy and safety of liraglutide once daily (LIRA) to exenatide twice daily (EXEN) in adult patients with type 2 diabetes, few studies have explored the associated per-patient costs of glycemic goal achievement of their use in a real-world clinical setting., Methods: This retrospective cohort study used integrated medical and pharmacy claims linked with glycated hemoglobin A1C (A1C) results from the IMS Patient-Centric Integrated Data Warehouse. Patients' ≥18 years and naïve to incretin therapies during a 6-month pre-index period, with ≥1 prescription for LIRA or EXEN between January 2010 and December 2010, were included. Patients with evidence of insulin use (pre- or post-index) were excluded. Only patients who were persistent on their index treatment during a 180-day post-index period were included. Follow-up A1C assessments were based on available laboratory data within 45 days before or after the 6-month post-index point in time. Diabetes-related pharmacy costs over the 6-month post-index period were captured and included costs for both the index drugs and concomitant diabetes medications., Results: 234 LIRA and 182 EXEN patients were identified for the analysis. The adjusted predicted diabetes-related pharmacy costs per patient over the 6-month post-index period were higher for LIRA compared to EXEN ($2,002 [95% confidence interval (CI): $1,981, $2,023] vs. $1,799 [95% CI: $1,778, $1,820]; P < 0.001). However, a higher adjusted predicted percentage of patients on LIRA reached A1C < 7% goal (64.4% [95% CI: 63.5, 65.3] vs. 53.6% [95% CI: 52.6, 54.6]; P < 0.05), translating into lower average diabetes-related pharmacy costs per successfully treated patient for LIRA as compared to EXEN ($3,108 vs. $3,354; P < 0.0001)., Conclusions: Although predicted diabetes-related pharmacy costs were greater with LIRA vs. EXEN, a higher proportion of patients on LIRA achieved A1C < 7%, resulting in a lower per-patient cost of A1C goal achievement with LIRA compared to EXEN.

Introduction: Type 2 diabetes mellitus (T2DM) progression often results in treatment intensification with injectable therapy to maintain glycemic control. Using pilot data from the Initiation of New Injectable Treatment Introduced after Anti-diabetic Therapy with Oral-only Regimens study, real-world treatment patterns among T2DM patients initiating injectable therapy with insulin glargine or liraglutide were assessed., Methods: This was a retrospective analysis of claims from the OptumInsight™ (OI; January 1, 2010 to July 30, 2010) and HealthCore(®) (HC; January 1, 2010 to June 1, 2010) health insurance databases. Baseline characteristics, health care resource utilization, and costs were compared between adults with T2DM initiating injectable therapy with insulin glargine pen versus liraglutide. Follow-up outcomes, including glycated hemoglobin A1c (A1C), hypoglycemia, health care utilization, and costs, were assessed., Results: At baseline, almost one in three liraglutide patients (OI, n = 363; HC, n = 521) had A1C <7.0%, while insulin glargine patients (OI, n = 498; HC, n = 1,188) had poorer health status, higher A1C (insulin glargine: 9.8% and 9.1% versus liraglutide: 7.9% and 7.7%, OI and HC, respectively, both P < 0.001), and were less likely to be obese (insulin glargine: 10.8% and 9.2% versus liraglutide: 17.4% and 18.8%, OI and HC, respectively, both P < 0.01). The percentage of patients experiencing a hypoglycemic event was numerically higher for insulin pen use for both cohorts (OI 4.4% versus 3.0%; HC 6.2% versus 2.3%). During follow-up, in the insulin glargine cohort, annualized diabetes-related costs remained unchanged ($8,344 versus $7,749 OI, and $7,094 versus $7,731 HC), despite a significant increase in pharmacy costs, due to non-significant decreases in medical costs, while the liraglutide cohort had a significant increase in annualized diabetes-related costs ($4,510 versus $7,731 OI, and $4,136 versus $7,111 HC; both P < 0.001) due to a non-significant increase in medical costs coupled with a significant increase in pharmacy costs., Conclusion: These descriptive data identified differences in demographic and baseline clinical characteristics among patients initiating injectable therapies. The different health care utilization and cost patterns warrant further cost-effectiveness analysis.

Background: Effective glycemic control can reduce the risk of serious micro- and macrovascular complications in type 2 diabetes. However, many patients fail to reach glycemic targets due partly to low efficacy and adverse effects of treatment such as hypoglycemia or weight gain., Objective: To evaluate the short-term cost-effectiveness of liraglutide versus sitagliptin, in terms of cost per patient reaching a glycated hemoglobin (HbA1c) target with no hypoglycemia and no weight gain after 52 weeks, based on a recently published trial. , Methods: Data were taken from a 52-week randomized, controlled trial (NCT00700817) in which adults with type 2 diabetes (mean age = 55 years, HbA1c = 8.4%, body mass index = 33 kg/m2) failing metformin monotherapy were randomly allocated to receive either liraglutide 1.2 mg, liraglutide 1.8 mg, or sitagliptin 100 mg daily, in addition to metformin. For the cost-effectiveness analysis, the proportion of patients achieving a clinically relevant composite endpoint, defined as HbA1c  less than  7.0%, with no reported hypoglycemia 
and no gain in body weight, was estimated using logistic regression. Trial data showed that 38.9% of patients on liraglutide 1.2 mg and 49.9% on liraglutide 1.8 mg achieved the composite endpoint, compared with 18.6% on sitagliptin at 52 weeks. Costs of antihyperglycemia medications were accounted for based on published wholesale acquisition costs in 2012 U.S. dollars. , Results: Overall pharmacy costs (needle costs included) were higher for patients on liraglutide than sitagliptin. The cost per patient achieving an HbA1c less than 7% was lowest for patients receiving liraglutide 1.2 mg ($7,993) and highest for patients receiving sitagliptin ($11,570). When expressed as the mean cost per patient reaching target HbA1c with no hypoglycemia or weight gain (cost of control), costs were notably lower on liraglutide than on sitagliptin. Annual mean costs of control were $10,335 on liraglutide 1.2 mg and $11,755 on liraglutide 1.8 mg versus $16,858 on sitagliptin., Conclusion: The mean cost per patient achieving control, defined as reaching HbA1c target with no hypoglycemia or weight gain, was lower with liraglutide than with sitagliptin based on data from a recently published 52-week clinical trial.

Objectives: The aim of this study was to evaluate the long-term cost-utility of liraglutide versus glimepiride as add-on therapy to metformin in patients with type 2 diabetes mellitus (T2DM), based on the results of clinical trial conducted in Asian population., Methods: The validated UKPDS Outcomes Model was used to project life expectancy, quality adjusted life-years (QALYs), incidence of diabetes-related complication and cost of complications in patients receiving those regimens. Baseline cohort characteristics and treatment effects were derived from an Asian study. China-specific complication costs and utility score were taken from local studies. Patients' outcomes were modeled for 30 years and incremental cost-effectiveness ratios were calculated for liraglutide compared with glimepiride from the healthcare system perspective. Both future costs and clinical benefits were discounted at 3 percent. Sensitivity analyses were performed., Results: Over a period of 30 years, compared with glimepiride, liraglutide 1.8 mg was associated with improvements in life expectancy (0.1 year) and quality adjusted life-year (0.168 QALY), and a reduced incidence of diabetes-related complications leading to an incremental cost-effectiveness ratio per QALY gained versus glimepiride of CNY 25,6871 (DEC 2010, 1 USD = 6.6227 CNY)., Conclusions: Long-term projections indicated that liraglutide was associated with increased life expectancy, QALYs, and reduced complication incidences comparing with glimepiride. When the UK cost of liraglutide was discounted by 38 percent, liraglutide would be a cost-effective option in China from the healthcare system perspective using the 3X GDP/capita per QALY as the WTP threshold.

Aim: To investigate the cost-effectiveness of liraglutide as add-on to metformin vs. glimepiride or sitagliptin in patients with Type 2 diabetes uncontrolled with first-line metformin., Methods: Data were sourced from a clinical trial comparing liraglutide vs. glimepiride, both in combination with metformin, and a clinical trial comparing liraglutide vs. sitagliptin, both as add-on to metformin. Only the subgroup of patients in whom liraglutide was added to metformin monotherapy was included in the cost-utility analysis. The CORE Diabetes Model was used to simulate outcomes and costs with liraglutide 1.2 and 1.8 mg vs. glimepiride and vs. sitagliptin over patients' lifetimes. Treatment effects were taken directly from the trials. Costs and outcomes were discounted at 3.5% per annum and costs were accounted from a third-party payer (UK National Health System) perspective., Results: Treatment with liraglutide 1.2 and 1.8 mg resulted, respectively, in mean increases in quality-adjusted life expectancy of 0.32 ± 0.15 and 0.28 ± 0.14 quality-adjusted life years vs. glimepiride, and 0.19 ± 0.15 and 0.31 ± 0.15 quality-adjusted life years vs. sitagliptin, and was associated with higher costs of £ 3003 ± £ 678 and £ 4688 ± £ 639 vs. glimepiride, and £ 1842 ± £ 751 and £ 3224 ± £ 683 vs. sitagliptin, over a patient's lifetime. Both liraglutide doses were cost-effective, with incremental cost-effectiveness ratios of £ 9449 and £ 16,501 per quality-adjusted life year gained vs. glimepiride, and £ 9851 and £ 10,465 per quality-adjusted life year gained vs. sitagliptin, respectively., Conclusions: Liraglutide, added to metformin monotherapy, is a cost-effective option for the treatment of Type 2 diabetes in a UK setting., (© 2011 The Authors. Diabetic Medicine © 2011 Diabetes UK.)

Objective: The safety and efficacy of the GLP-1 receptor agonists exenatide BID (exenatide) and liraglutide for treating type 2 diabetes mellitus (T2DM) have been established in clinical trials. Effective treatments may lower overall treatment costs. This study examined cost offsets and medication adherence for exenatide vs liraglutide in a large, managed care population in the US., Methods: This was a retrospective cohort analysis comprising adult patients with T2DM who initiated exenatide or liraglutide between 1/1/2010 and 6/30/2010 and had 6 months pre-index and post-index continuous eligibility. Patients were propensity score-matched to controls for baseline differences. Medication adherence was measured by proportion of days covered (PDC). Paired t-test and McNemar's test were used to compare outcomes., Results: Matched exenatide and liraglutide cohorts (n=1347 pairs) had similar average total 6-month follow-up costs ($6688 vs $7346). However, exenatide patients had significantly lower mean pharmacy costs ($2925 vs $3272, p<0.001). Among liraglutide patients, patients receiving the 1.8 mg dose had significantly higher average total costs compared to those receiving the 1.2 mg dose ($8031 vs $6536, p=0.026), with higher mean pharmacy costs in the 1.8 mg cohort ($3935 vs $3146, p<0.001). There were no significant differences in inpatient or outpatient costs or medication adherence between groups (mean PDC: exenatide 56% vs liraglutide 57%, p=0.088)., Limitations: The study assumed that all information needed for case classification and matching of cohorts was present and not differential across cohorts. The study did not control for covariates that were unavailable, such as HbA1c and duration of diabetes., Conclusions: Patients initiating exenatide vs liraglutide for T2DM had similar medication adherence and total healthcare costs; however, exenatide patients had significantly lower total pharmacy costs. Patients prescribed 1.8 mg liraglutide had significantly higher costs compared to those on 1.2 mg.

Objective: The purpose of this study was to investigate the preferences of people with diabetes for liraglutide vs other glucose lowering drugs, based on outcomes of clinical trials., Methods: Willingness to pay (WTP) for diabetes drug treatment was assessed by combining results from a recent WTP study with analysis of results from the Liraglutide Effect and Action in Diabetes (LEAD) programme. The LEAD programme included six randomised clinical trials with 3967 participants analysing efficacy and safety of liraglutide 1.2 mg (LEAD 1-6 trials), rosiglitazone (LEAD 1 trial), glimepiride (LEAD 2-3 trials), insulin glargine (LEAD 5 trial), and exenatide (LEAD 6 trial). The WTP survey used discrete choice experimental (DCE) methodology to evaluate the convenience and clinical effects of glucose lowering treatments., Results: People with type 2 diabetes were prepared to pay an extra €2.64/day for liraglutide compared with rosiglitazone, an extra €1.94/day compared with glimepiride, an extra €3.36/day compared with insulin glargine, and an extra €0.81/day compared with exenatide. Weight loss was the largest component of WTP for liraglutide compared with rosiglitazone, glimepiride, and insulin glargine. Differences in the administration of the two drugs was the largest component of WTP for liraglutide (once daily anytime) compared with exenatide (twice daily with meals). A limitation of the study was that it was based on six clinical trials where liraglutide was the test drug, but each trial had a different comparator, therefore the clinical effects of liraglutide were much better documented than the comparators., Conclusions: WTP analyses of the clinical results from the LEAD programme suggested that participants with type 2 diabetes were willing to pay appreciably more for liraglutide than other glucose lowering treatments. This was driven by the relative advantage of weight loss compared with rosiglitazone, glimepiride, and insulin glargine, and administration frequency compared with exenatide.

Liraglutide (Victoza®) is a subcutaneously administered glucagon-like peptide-1 (GLP-1) receptor agonist produced by recombinant DNA technology and used as an adjunct to diet and exercise in the treatment of adults with type 2 diabetes mellitus. This article reviews the clinical efficacy and tolerability of liraglutide in adults with type 2 diabetes, and provides a summary of its pharmacological properties. Recently published pharmacoeconomic studies of liraglutide are also reviewed. Administered subcutaneously, liraglutide (usually 1.2 or 1.8 mg once daily) generally produced greater improvements in glycaemic control than active comparators or placebo when administered as monotherapy or in combination with one or two oral antidiabetic drugs (OADs) to adults with type 2 diabetes in numerous randomized, controlled phase III trials. These included six trials in the LEAD trial programme that was designed to evaluate the efficacy and safety of liraglutide across a continuum of antihyperglycaemic management for patients with type 2 diabetes. Liraglutide was generally well tolerated, with a low risk of hypoglycaemia evident, in the phase III trials. The most common adverse events were gastrointestinal and included nausea and diarrhoea; most events were mild to moderate in severity and decreased in incidence over time. In conclusion, liraglutide has an important place in the management of adults with type 2 diabetes across a continuum of care. As well as providing effective glycaemic control, liraglutide improves pancreatic β-cell function and leads to bodyweight loss, thereby addressing some of the unmet needs of patients treated with traditional OADs.

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of liraglutide in the treatment of type 2 diabetes mellitus, based upon the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal process. The manufacturer proposed the use of liraglutide as a second or third drug in patients with type 2 diabetes whose glycaemic control was unsatisfactory with metformin, with or without a second oral glucose-lowering drug. The submission included six manufacturer-sponsored trials that compared the efficacy of liraglutide against other glucose-lowering agents. Not all of the trials were relevant to the decision problem. The most relevant were Liraglutide Effects and Actions in Diabetes 5 (LEAD-5) (liraglutide used as part of triple therapy and compared against insulin glargine) and LEAD-6 [liraglutide in triple therapy compared against another glucagon-like peptide-1 agonist, exenatide]. Five of the six trials were published in full and one was then unpublished. Two doses of liraglutide, 1.2 and 1.8 mg, were used in some trials, but in the two comparisons in triple therapy, against glargine and exenatide, only the 1.8-mg dose was used. Liraglutide in both doses was found to be clinically effective in lowering blood glucose concentration [glycated haemoglobin (HbA1c)], reducing weight (unlike other glucose-lowering agents, such as sulphonylureas, glitazones and insulins, which cause weight gain) and also reducing systolic blood pressure (SBP). Hypoglycaemia was uncommon. The ERG carried out meta-analyses comparing the 1.2- and 1.8-mg doses of liraglutide, which suggested that there was no difference in control of diabetes, and only a slight difference in weight loss, insufficient to justify the extra cost. The cost-effectiveness analysis was carried out using the Center for Outcomes Research model. The health benefit was reported as quality-adjusted life-years (QALYs). The manufacturer estimated the cost-effectiveness to be £ 15,130 per QALY for liraglutide 1.8 mg compared with glargine, £ 10,054 per QALY for liraglutide 1.8 mg compared with exenatide, £ 10,465 per QALY for liraglutide 1.8 mg compared with sitagliptin, and £ 9851 per QALY for liraglutide 1.2 mg compared with sitagliptin. The ERG conducted additional sensitivity analyses and concluded that the factors that carried most weight were: in the comparison with glargine, the direct utility effects of body mass index (BMI) changes and SBP, with some additional contribution from HbA1c, in the comparison with exenatide, HbA1c, with some additional effects from cholesterol and triglycerides in the comparison with sitagliptin, HbA1c and direct utility effects of BMI changes. The European Medicines Agency has approved liraglutide in dual therapy with other oral glucose-lowering agents. NICE guidance recommends the use of liraglutide 1.2 mg in triple therapy when glycaemic control remains or becomes inadequate with a combination of two oral glucose-lowering drugs. The use of liraglutide 1.2 mg in a dual therapy is indicated only in patients who are intolerant of, or have contraindications to, three oral glucose-lowering drugs. The use of liraglutide 1.8 mg was not approved by NICE. The ERG recommends research into the (currently unlicensed) use of liraglutide in combination with long-acting insulin.

Background: Many patients with type 2 diabetes mellitus (T2DM) are not able to maintain adequate HbA(1c) control (<7.0%), even at maximal dosage levels of one or two oral agents, and are at increased risk for diabetes-related complications., Objective: To estimate the cost-effectiveness of a once-daily GLP-1 analog Victoza [Novo Nordisk] versus a thiazolidinedione (TZD), rosiglitazone in patients with T2DM. Both treatment groups included background therapy with glimepiride., Research Design and Methods: The CORE Diabetes Model (CDM) was used to project and compare 35-year clinical and economic outcomes associated with liraglutide 1.2 mg + glimepiride and liraglutide 1.8 mg + glimepiride versus rosiglitazone 4 mg + glimepiride. Baseline cohort characteristics (HbA(1c) (8.4%), age, duration of disease, sex, body-mass index (BMI), blood pressure, and lipids) were based on the Liraglutide Effect and Action in Diabetes-1 (LEAD-1) trial., Outcomes: Primary outcomes included life expectancy (LE), quality-adjusted life-years (QALYs), total costs and incremental cost-effectiveness ratios (ICERs). results: When compared to rosiglitazone, liraglutide 1.2 mg and 1.8 mg increased mean LE by 0.968 and 1.041 years, and QALYs by 0.764 and 0.837, respectively. Total lifetime costs increased by $26,094 for liraglutide 1.2 mg versus rosiglitazone, and by $47,041 for liraglutide 1.8 mg versus rosiglitazone. ICERs for liraglutide 1.2 mg versus rosiglitazone and 1.8 mg versus rosiglitazone were $34,147 and $56,190, respectively., Conclusions: Compared to rosiglitazone 4 mg plus glimepiride, liraglutide (particularly at the 1.2-mg dose) plus glimepiride is a cost-effective treatment option for improving glucose control in T2DM. Limitations include the projection of short term efficacy results from randomized control trials to longer time horizons. In addition, clinical acceptance and overall use of rosiglitazone in the treatment of diabetes has continued to fall since publication of the clinical trial upon which this modeling analyses was based.

Background: Nearly half of all US patients with type 2 diabetes mellitus (T2DM) are unable to maintain adequate glycosylated hemoglobin (HbA₁(c)) control (ie, <7.0%)., Objective: The aim of this work was to determine the long-term cost-effectiveness of incretin-based therapy with once-daily liraglutide (vs twice-daily exenatide) combined with metformin, glimepiride, or both for the treatment of T2DM., Methods: Patient data were obtained from the Liraglutide Effect and Action in Diabetes 6 (LEAD 6) trial. Baseline data included mean HbA₁(c) (8.15%), age (56.7 years), disease duration (8 years), sex, body mass index, blood pressure, lipid levels, cardiovascular and renal risk factors, and other complications. The IMS Center for Outcomes Research Diabetes Model was used to project and compare lifetime (ie, 35-year) clinical and economic outcomes for once-daily liraglutide 1.8 mg compared with twice-daily exenatide 10 (ig, each used as add-on therapy with maximum-dose metformin and/or glimepiride. Treatment-effect assumptions were also derived from the LEAD 6 trial. Transition probabilities, utilities, and complication costs were obtained from published sources. All outcomes were discounted at 3% per annum, and the analysis was conducted from the perspective of a third-party payer in the United States., Results: The base-case analysis indicated that, compared with exenatide, liraglutide add-on therapy was associated with a mean (SD) increase in life expectancy of 0.187 (0.250) years and an increase in qualityadjusted life-years of 0.322 (0.164) years. Compared with exenatide, total lifetime treatment costs for liraglutide were $12,956 higher, yielding an incremental costeffectiveness ratio (ICER) of $40,282. However, the costs of diabetes-related complications were lower with liraglutide than with exenatide ($49,784 vs $52,429, respectively). Sensitivity analysis indicated that setting patient HbA(1c) levels at the 95% upper limit reduced the ICER for liraglutide compared with exenatide to $33,086., Conclusion: In this model analysis using published clinical data and current medication acquisition price assumptions, liraglutide (in combination with metformin and/or glimepiride) appeared to be cost-effective in the US payer setting over a 35-year time horizon., (Copyright © 2010 Excerpta Medica Inc. All rights reserved.)

Objective: To evaluate the impact of Medicare Part D coverage gap (donut hole) on adherence to diabetes medications., Study Design: Retrospective cohort analysis based on pharmacy claims data., Methods: The sample included 12,881 Medicare Part D beneficiaries with diabetes who entered the coverage gap in 2008. Sample patients had 3 different levels of coverage in the donut hole: no coverage, generic drug coverage only, and both generic and brand-name drug coverage. Adherence was measured by the proportion of days covered. We used a difference-in-difference model to evaluate the effect of coverage gap on adherence., Results: In the donut hole, the average copayment for diabetes medications increased substantially for beneficiaries with no coverage and beneficiaries with generic drug coverage only, whereas the average copayment for beneficiaries with both generic and brand-name medication coverage declined slightly. Compared with beneficiaries with full coverage of both generic and brand-name drugs, beneficiaries with no coverage (odds ratio[OR] = 0.617, P <.0001, 95% confidence interval [CI] = 0.523, 0.728) and beneficiaries with generic drug coverage only (OR = 0.702, P <.0001, 95% CI = 0.604, 0.816) were significantly less likely to be adherent after entering the donut hole. The difference between having generic coverage and no coverage was not significant (P = .1586)., Conclusions: The coverage gap in the Medicare Part D program has a significant negative impact on medication adherence among beneficiaries with diabetes. Availability of brand-name drug coverage in the donut hole is critical to adherence to diabetes medications.

Study Objective: To project and compare long-term outcomes of morbidity and mortality, and costs of complications of type 2 diabetes mellitus from a randomized controlled trial of patients receiving liraglutide versus glimepiride monotherapy., Design: Mathematic simulation using the validated Center for Outcomes Research (CORE) Diabetes Model, calibrated to baseline patient characteristics from a short-term, randomized, controlled trial of liraglutide and glimepiride monotherapies (Liraglutide Effect and Action in Diabetes [LEAD]-3 trial) and using data from long-term outcomes studies., Setting: Simulated routine clinical practice., Patients: Seven hundred forty-six patients with type 2 diabetes who participated in the LEAD-3 trial, and three hypothetical cohorts of 5000 patients each that were based on the baseline characteristics of the patients in the LEAD-3 trial. The patients in the LEAD-3 trial were randomly assigned to monotherapy with liraglutide 1.2 mg/day (251 patients), liraglutide 1.8 mg/day (247 patients), or glimepiride 8 mg/day (248 patients)., Measurements and Main Results: The impact of the three treatments for type 2 diabetes on survival and cumulative incidence of cardiovascular, ocular, or renal events and costs were estimated at three time periods: 10, 20, and 30 years. Simulations predicted improved survival for liraglutide 1.8 and 1.2 mg at all three time points compared with glimepiride. Survival benefits were greatest after 30 years of follow-up: 16.5%, 13.6%, and 7.3%, respectively. The frequency of nonfatal renal and ocular events was lower for both liraglutide doses than for glimepiride. The rate of neuropathies leading to first or recurrent amputation was higher for glimepiride compared with both liraglutide doses. The average cumulative cost/patient was higher for glimepiride compared with liraglutide 1.2 mg and liraglutide 1.8 mg., Conclusion: With use of the CORE Diabetes Model and data from the LEAD-3 trial, long-term projected survival, diabetes complications, and costs favored liraglutide 1.2- and 1.8-mg monotherapies compared with glimepiride in the treatment of type 2 diabetes.