Valuing injection frequency and other attributes of type 2 diabetes treatments in Australia: a discrete choice experiment.

BACKGROUND: Multiple pharmacotherapy options are available to control blood glucose in Type 2 Diabetes Mellitus (T2DM). Patients and prescribers may have different preferences for T2DM treatment attributes, such as mode and frequency of administration, based on their experiences and beliefs which may impact adherence. As adherence is a pivotal issue in diabetes therapy, it is important to understand what patients value and how they trade-off the risks and benefits of new treatments. This study aims to investigate the key drivers of choice for T2DM treatments, with a focus on injection frequency, and explore patients' associated willingness-to-pay. METHODS: A discrete choice experiment (DCE) was used to present patients with a series of trade-offs between different treatment options, injectable and oral medicines that were made up of 10 differing levels of attributes (frequency and mode of administration, weight change, needle type, storage, nausea, injection site reactions, hypoglycaemic events, instructions with food and cost). A sample of 171 Australian consenting adult T2DM patients, of which 58 were receiving twice-daily injections of exenatide and 113 were on oral glucose-lowering treatments, completed the national online survey. An error components model was used to estimate the relative priority and key drivers of choice patients place on different attributes and to estimate their willingness to pay for new treatments. RESULTS: Injection frequency, weight change, and nausea were shown to be important attributes for patients receiving injections. Within this cohort, a once-weekly injection generated an additional benefit over a twice-daily injection, equivalent to a weighted total willingness to pay of AUD$22.35 per month. CONCLUSIONS: Based on the patient preferences, the importance of frequency of administration and other non-health benefits can be valued. Understanding patient preferences has an important role in health technology assessment, as the identification of the value as well as the importance weighting for each treatment attribute may assist with funding decisions beyond clinical trial outcomes.

The pattern of prescribing of glucose modulating agents for type 2 diabetes in general practices in England 2016/17.

BACKGROUND: In the financial year 2016/17 there were 52.0 million items prescribed for diabetes at a total net ingredient cost of £983.7 million - up from 28.9 million prescription items and £572.4 million in 2006/07. Anti-diabetes drugs (British National Formulary section 6.1.2) make up 45.1 per cent of the total £983.7 million net ingredient cost of drugs used in diabetes and account for 72.0 per cent of prescription items for all diabetes prescribing. METHODS: We examined the way that agents licensed to treat type 2 diabetes were used across GP practices in England in the year 2016/2017. Analysis was at a GP practice level not at the level of patient data. RESULTS: Annual prescribing costs / patient / medication type for monotherapy varied considerable from £11/year for gliclazide and glimepiride to £885/year for Liraglutide. The use of SGLT-2i agents grew strongly at 70% per annum to around 100,000 DDD with prescriptions seen in 95% of GP practices. Liraglutide expenditure (11% of total) was high for a relatively small number of patients (1.3% of Defined Daily Doses), with still significant spend on exenatide. Liraglutide use significantly exceeded that of other glucagon-like peptide-1 (GLP-1) agonists. CONCLUSIONS: Our work demonstrates the significant cost of medication to modulate tissue glucose levels in type 2 diabetes and the dominance of some non-generic preparations in terms of number of prescriptions and overall spend. There are some older sulphonylureas in use, which should not generally be prescribed. Regular audit of patient treatment at a general practice level will ensure appropriate targeted use of licensed medications and of their cost effectiveness.

Cost Effectiveness of Exenatide Once Weekly Versus Insulin Glargine and Liraglutide for the Treatment of Type 2 Diabetes Mellitus in Greece.

OBJECTIVE: The objective of this study was to evaluate the long-term cost effectiveness of exenatide once weekly (ExQW) versus insulin glargine (IG) or liraglutide 1.2 mg (Lira1.2mg) for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on oral antidiabetic drug (OAD) therapy in Greece. METHODS: The published and validated Cardiff Diabetes Model was used to project clinical and economic outcomes over a patient's lifetime. Clinical data were retrieved from a head-to-head clinical trial (DURATION 3) and a published network meta-analysis comparing ExQW with IG or Lira1.2mg, respectively. Following a Greek third-party payer perspective, direct medical costs related to drug acquisition, consumables, developed micro- and macrovascular complications, maintenance treatment, as well as treatment-related adverse events were considered. Cost and utility data were extracted from literature and publicly available official sources and assigned to model parameters to calculate total quality-adjusted life-years (QALYs) and total costs as well as incremental cost-effectiveness ratios (ICERs). Sensitivity analyses explored the impact of changes in input data. RESULTS: Over a patient's lifetime, ExQW was associated with 0.458 or 0.039 incremental QALYs compared with IG or Lira1.2mg, respectively, at additional costs of €2061 or €110, respectively. The ICER for ExQW was €4499/QALY compared with IG and €2827/QALY compared with Lira1.2mg. Results were robust across various one-way and scenario analyses. At the defined willingness-to-pay threshold of €36,000/QALY, probabilistic sensitivity analysis showed that ExQW had a 100 or 88.2% probability of being cost effective relative to IG or Lira1.2mg, respectively. CONCLUSIONS: ExQW was estimated to be cost effective relative to IG or Lira1.2mg for the treatment of T2DM in adults not adequately controlled on OAD therapy in Greece.

Healthcare resource utilization and related financial costs associated with glucose lowering with either exenatide or basal insulin: A retrospective cohort study.

AIMS: Type 2 diabetes is a major health problem placing increasing demands on healthcare systems. Our objective was to estimate healthcare resource use and related financial costs following treatment with exenatide-based regimens prescribed as once-weekly (EQW) or twice-daily (EBID) formulations, compared with regimens based on basal insulin (BI). MATERIALS AND METHODS: This retrospective cohort study used data from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES). Patients with type 2 diabetes who received exenatide or BI between 2009 and 2014 as their first recorded exposure to injectable therapy were selected. Costs were attributed to primary care contacts, diabetes-related prescriptions and inpatient admissions using standard UK healthcare costing methods (2014 prices). Frequency and costs were compared between cohorts before and after matching by propensity score using Poisson regression. RESULTS: Groups of 8723, 218 and 2180 patients receiving BI, EQW and EBID, respectively, were identified; 188 and 1486 patients receiving EQW and EBID, respectively, were matched 1:1 to patients receiving BI by propensity score. Among unmatched cohorts, total crude mean costs per patient-year were £2765 for EQW, £2549 for EBID and £4080 for BI. Compared with BI, the adjusted annual cost ratio (aACR) was 0.92 (95% CI, 0.91-0.92) for EQW and 0.82 (95% CI, 0.82-0.82) for EBID. Corresponding costs for the propensity-matched subgroups were £2646 vs £3283 (aACR, 0.80, 0.80-0.81) for EQW vs BI and £2532 vs £3070 (aACR, 0.84, 0.84-0.84) for EBID vs BI. CONCLUSION: Overall, exenatide once-weekly and twice-daily-based regimens were associated with reduced healthcare resource use and costs compared with basal-insulin-based regimens.

The Influence of Varying Cost Formats on Preferences.

BACKGROUND: Numerous studies have found that cost strongly influences patients' decision making. The objective of this study was to explore the impact of varying cost formats on patients' preferences. METHODS: Mechanical Turk workers completed a choice-based conjoint (CBC) survey. The CBC survey was designed to examine stated preferences for the use of second-line agents to treat diabetes across 5 attributes: route of administration, efficacy, risk of low blood sugar, frequency of checking blood sugar levels, and cost. We developed 7 versions of the CBC survey that were identical except for the cost attribute. We described cost in terms of: Affordability, Monthly Co-pay, Dollar Sign Rating, How Expensive, or How Cheap compared with other medications, Working Hours Equivalent (per mo) and Percent of Monthly Income. The resulting part-worth utilities were used to calculate the relative importance of cost and to estimate treatment preferences for exenatide, a sulfonylurea, and insulin. RESULTS: The relative impact of cost varied significantly across the 7 formats. Cost had the greatest influence on participants' decisions when framed in terms of Affordability [mean (SD) relative importance, 37.3 (0.9)] and the lowest influence when framed in terms of How Cheap (compared with other drugs) [12.1 (0.9)]. A sulfonylurea was strongly preferred across 4 of the 7 formats. Preference for insulin, the most effective, albeit riskiest, option was low across all cost formats. CONCLUSIONS: The format used to describe cost affects how the attribute impacts patients' preferences. Individuals are most cost-sensitive when cost is framed in terms of affordability and least cost-sensitive when cost is described in terms of how cheap the medication is compared with others.

Cost-effectiveness analysis of exenatide once-weekly versus dulaglutide, liraglutide, and lixisenatide for the treatment of type 2 diabetes mellitus: an analysis from the UK NHS perspective.

OBJECTIVE: To assess the cost-effectiveness of exenatide 2 mg once-weekly (EQW) compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg and 1.8 mg once-daily (QD), and lixisenatide 20 µg QD for the treatment of adult patients with type 2 diabetes mellitus (T2DM) not adequately controlled on metformin. METHODS: The Cardiff Diabetes Model was applied to evaluate cost-effectiveness, with treatment effects sourced from a network meta-analysis. Quality-adjusted life years (QALYs) were calculated with health-state utilities applied to T2DM-related complications, weight changes, hypoglycemia, and nausea. Costs (GBP £) included drug treatment, T2DM-related complications, severe hypoglycemia, nausea, and treatment discontinuation due to adverse events. A 40-year time horizon was used. RESULTS: In all base-case comparisons, EQW was associated with a QALY gain per patient; 0.046 vs dulaglutide 1.5 mg; 0.102 vs liraglutide 1.2 mg; 0.043 vs liraglutide 1.8 mg; and 0.074 vs lixisenatide 20 µg. Cost per patient was lower for EQW than for liraglutide 1.8 mg (-£2,085); therefore, EQW dominated liraglutide 1.8 mg. The cost difference per patient between EQW and dulaglutide 1.5 mg, EQW and liraglutide 1.2 mg, and EQW and lixisenatide 20 µg was £27, £103, and £738, respectively. Cost per QALY gained with EQW vs dulaglutide 1.5 mg, EQW vs liraglutide 1.2 mg, and EQW vs lixisenatide 20 µg was £596, £1,004, and £10,002, respectively. In the probabilistic sensitivity analysis, the probability that EQW is cost-effective ranged from 76-99%. CONCLUSION: Results suggest that exenatide 2 mg once-weekly is cost-effective over a lifetime horizon compared to dulaglutide 1.5 mg QW, liraglutide 1.2 mg QD, liraglutide 1.8 mg QD, and lixisenatide 20 µg QD for the treatment of T2DM in adults not adequately controlled on metformin alone.

The cost-effectiveness of exenatide twice daily (BID) vs insulin lispro three times daily (TID) as add-on therapy to titrated insulin glargine in patients with type 2 diabetes.

OBJECTIVE: To evaluate the cost-effectiveness of exenatide twice daily (BID) vs bolus insulin lispro three times daily (TID) as add-on therapy when glycemic control is sub-optimal with titrated basal insulin glargine and metformin. METHODS: The analysis was based on the recent 4B Study, which compared exenatide BID and lispro TID as add-on therapies in subjects with type 2 diabetes insufficiently controlled, despite titrated insulin glargine. The Cardiff Diabetes Model was used to simulate patient costs and health benefits beyond the 4B Study. The Swedish healthcare perspective was adopted for this analysis; costs are reported in €EUR to aid interpretation. The main outcome measure was the cost per quality-adjusted life-year (QALY) gained with exenatide BID compared to lispro TID. RESULTS: Exenatide BID was associated with an incremental cost of €1,270 and a QALY increase of +0.64 compared with lispro TID over 40 years. The cost per QALY gained with exenatide BID compared with lispro TID was €1,971, which is within conventional limits of cost-effectiveness. Cost-effectiveness results were generally robust to alternative assumptions and values for key model parameters. LIMITATIONS: Extrapolation of trial data over the longer term can be influenced by modeling and parameter uncertainty. Cost-effectiveness results were generally insensitive to alternative values of key model input parameters and across scenarios. CONCLUSIONS: The addition of exenatide BID rather than insulin lispro to basal insulin is associated with similar or better clinical outcomes. Illustrated from the Swedish healthcare perspective, analysis with the Cardiff Diabetes Model demonstrated that exenatide BID represents a cost-effective treatment alternative to lispro TID as add-on therapy in type 2 diabetes patients insufficiently controlled on basal insulin.

Comparative persistence and adherence with newer anti-hyperglycemic agents to treat patients with type 2 diabetes in the United States.

OBJECTIVES: Non-adherence and non-persistence to anti-hyperglycemic agents are associated with worse clinical and economic outcomes in patients with type 2 diabetes. This study evaluated treatment persistence and adherence across newer anti-hyperglycemic agents (canagliflozin, dapagliflozin, sitagliptin, saxagliptin, linagliptin, liraglutide, or exenatide). METHODS: This retrospective cohort study of Truven Health Analytics Marketscan databases included adult patients with type 2 diabetes whose first pharmacy claim for a newer anti-hyperglycemic agent was between February 1, 2014 and July 31, 2014. Treatment persistence and adherence were assessed for 12 months after the first claim (post-index). Persistence was defined as no gap ≥90 days between the end of one pharmacy claim and the start of the next pharmacy claim post-index. Adherence used two definitions: proportion of days covered (PDC) and medication possession ratio (MPR). Multivariable analyses of non-persistence (hazard ratios) and adherence (odds ratios) were adjusted for baseline demographics, drug cost, clinical characteristics, and other anti-hyperglycemic agents. RESULTS: A total of 11,961 patients met all study selection criteria. Persistence rates at 12 months were significantly greater (p < 0.05 for each comparison) for canagliflozin 100 mg (61%) compared with dapagliflozin 5 mg (40%), dapagliflozin 10 mg (41%), sitagliptin (48%), saxagliptin (42%), linagliptin (52%), liraglutide (47%), exenatide (23%), and long-acting exenatide (39%). The persistence rate was greater (p < 0.05) for canagliflozin 300 mg (64%) vs canagliflozin 100 mg. Median adherence rates for canagliflozin 100 mg (MPR = 0.83; PDC = 0.79) and canagliflozin 300 mg (MPR = 0.92; PDC = 0.81) were greater than for the other index anti-hyperglycemic agents (MPR = 0.33-0.75; PDC = 0.33-0.72). Consistent results for treatment persistence and adherence were observed in multivariable analyses that were adjusted baseline characteristics. CONCLUSIONS: Canagliflozin was associated with better treatment persistence and treatment adherence compared with other anti-hyperglycemic agents in real-world settings.

Cost-effectiveness analysis of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese patients with Type 2 diabetes mellitus inadequately controlled by oral therapies.

OBJECTIVE: To estimate cost-effectiveness of exenatide twice daily (BID) vs insulin glargine once daily (QD) as add-on therapy in Chinese type 2 diabetes patients not well controlled by oral anti-diabetic (OAD) agents. METHODS: The Cardiff model was populated with data synthesized from three head-to-head randomized clinical trials of up to 30 weeks in China comparing exenatide BID vs insulin glargine as add-on therapies to oral therapies in the Chinese population. The Cardiff model generated outputs including macrovascular and microvascular complications, diabetes-specific mortality, costs, and quality-adjusted life years (QALYs). Cost and QALYs were estimated with a time horizon of 40 years at a discount rate of 3% from a societal perspective. RESULTS: Compared with insulin glargine plus OAD treatments, patients on exenatide BID plus OAD gained 1.88 QALYs, at an incremental cost saving of Chinese Renminbi (RMB) 114,593 (i.e., cost saving of RMB 61078/QALY). The cost-effectiveness results were robust to various sensitivity analyses including probabilistic sensitivity analysis. The variables with the most impact on incremental cost-effectiveness ratio included HbA1c level at baseline, health utilities decrement, and BMI at baseline. CONCLUSIONS: Compared with insulin glargine QD, exenatide BID as add-on therapy to OAD is a cost-effective treatment in Chinese patients inadequately controlled by OAD treatments.

The short-term cost-effectiveness of once-daily liraglutide versus once-weekly exenatide for the treatment of type 2 diabetes mellitus in the United States.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease with substantial morbidity, mortality, and economic impacts. Glucagon-like peptide-1 (GLP-1) receptor agonists, such as once-daily (QD) liraglutide and once-weekly (QW) exenatide, are FDA-approved treatment for T2DM. Head-to-head trials and meta-analyses comparing these agents have reported clinically meaningful improvements but small differences in glycemic control between both agents. In this study, we calculate and compare the cost-effectiveness implications of these alternative effectiveness outcomes. METHODS: We developed a decision model to evaluate the short-term cost-effectiveness of exenatide QW 2 mg versus liraglutide QD 1.8 mg in T2DM patients, with effectiveness measured as reduction in glycated hemoglobin (HbA1c). In the base case, the model tracks change in HbA1c and direct medical expenditure over a 6-month time horizon. We calculated and compared the cost per 1% reduction in HbA1c of models populated with clinical data from a head-to-head randomized, controlled trial (DURATION-6) and a network meta-analysis. Expenditure inputs were derived from wholesale acquisition costs and published sources. RESULTS: In the base case, 6-month expenditure for the liraglutide and exenatide strategies were $3,509 and $2,618, respectively. Using clinical data from DURATION-6 and the network meta-analysis, the liraglutide strategy had an incremental cost per 1% reduction in HbA1c of $4,773 and $27,179, respectively. The most influential model parameters were drug costs, magnitude of HbA1c reduction in patients on treatment for >1 month, and liraglutide gastrointestinal adverse event rate. In probabilistic sensitivity analyses (PSA) using DURATION-6 data, the exenatide strategy was optimal at willingness-to-pay levels below $4,800 per 1% reduction in HbA1c. In a PSA using meta-analysis data, the exenatide strategy was dominant. CONCLUSIONS: Our modeled results demonstrate that the effectiveness and cost-effectiveness of liraglutide QD 1.8 mg relative to exenatide QW 2 mg depend largely on the chosen source of the clinical data.

Off-label antiobesity treatment in patients without diabetes with GLP-1 agonists in clinical practice.

The aim of the work was to investigate whether continuation of treatment, side effects, and effect on weight loss of GLP-1 agonists in obese patients without diabetes are equally promising in daily clinical-practice-settings compared to controlled clinical trials. Obese patients without diabetes of our interdisciplinary obesity centre were treated off-label with GLP-1-agonists for different time periods. Application was started with low-dose and increased if side effects were tolerable. Monthly costs were € 125 for daily applications of 1.2 mg liraglutide or 10 µg exenatide twice daily. Data were obtained by telephone interviews about baseline characteristics, weight loss, sensation of satiation, duration of therapy, side effects, and reasons for discontinuation. Of 43 included cases (5 males, mean age 43±11 years, mean weight 107±24 kg, mean excess weight 35±21 kg) 7 were treated with exenatide and 36 with liraglutide. Excess weight loss in linear regression models was 6.7% per month (p <0.05) under control of age, sex, initial weight, and type of GLP-1 analogue treatment and did not significantly differ between liraglutide and exenatide. Overall, 58% of patients reported side effects mostly concerning the gastrointestinal tract. Surprisingly no patient reported vomiting. One patient developed a severe pancreatitis. At time of telephone interview only 30.2% were continuing treatment. Mean treatment duration was 2.98±2.71 months. Common reasons for discontinuation of treatment were no/little effect on weight loss (27.9%), intolerable side effects (20.9%), or financial reasons (14%). GLP-1 agonist treatment in obese patients without diabetes also correlates with significant weight loss in clinical practice. However, side effects and discontinuation of treatment are common. Therefore, long-term effect on weight loss might not be as promising as suggested by data from clinical trials.

Cost-effectiveness analysis of liraglutide versus sitagliptin or exenatide in patients with inadequately controlled Type 2 diabetes on oral antidiabetic drugs in Greece.

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.

Real-world cost-effectiveness: lower cost of treating patients to glycemic goal with liraglutide versus exenatide.

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.

Clinical effects of once-weekly exenatide for the treatment of type 2 diabetes mellitus.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, administration, dosage, place in therapy, and cost of extended-release exenatide are reviewed. SUMMARY: Regular-release exenatide has a half-life of 2.4 hours and is administered twice daily. In order to allow for once-weekly administration, exenatide was encapsulated in poly(lactic-co-glycolic acid) microspheres, a biodegradable polymer. After subcutaneous injection, the microspheres slowly degrade, and the drug is released. A single injection of extended-release exenatide reaches maximum plasma concentration after 4-8 hours and remains at therapeutic levels for 8-16 hours, depending on the dosage. Based on the pharmacokinetics of a single dose, researchers determined that 0.8- and 2-mg once-weekly doses were likely to maintain therapeutic levels in the serum. Patients who used extended-release exenatide monotherapy had significantly lower glycosylated hemoglobin (HbA1c) levels and lost more weight than those receiving sitagliptin or pioglitazone (p < 0.05). In combination with metformin, extended-release exenatide reduced HbA1c levels more than did insulin glargine. This new formulation reduced HbA1c levels by 1.5-1.9%, fasting blood glucose concentrations by 31-42 mg/dL, and weight by 2.3-3.7 kg. The most common adverse events were injection-site reactions and transient nausea. Postmarketing reports have described acute pancreatitis and acute necrotizing or hemorrhagic pancreatitis in patients treated with exenatide. The published average wholesale price for a one-month supply of extended-release exenatide 2 mg is $388. CONCLUSION: Extended-release exenatide taken once weekly is an effective second-line therapy for patients with type 2 diabetes who have not achieved glycemic goals with metformin alone.

Retrospective database analysis of the impact of prior authorization for type 2 diabetes medications on health care costs in a Medicare Advantage Prescription Drug Plan population.

BACKGROUND: Health plans and pharmacy benefit managers have implemented utilization management strategies for newer type 2 diabetes mellitus (T2DM) medications to control pharmacy expenditures. Little is known about the impact of utilization management strategies on overall health care costs and subsequent use of T2DM medications among members who request, but do not receive, a T2DM medication requiring prior authorization (PA).  OBJECTIVE: To examine the relationship between the receipt of a T2DM medication requiring PA, health care costs, and subsequent treatment for T2DM.  METHODS: A retrospective cohort study using pharmacy, medical, and laboratory claims data was conducted among Medicare Advantage Prescription Drug plan members with a denied claim for a T2DM medication requiring PA (sitagliptin, a dipeptidyl peptidase-4 inhibitor [DPP-4i], and exenatide, an incretin mimetic) between January 1, 2008, and June 30, 2009. Subjects were required to have 12 months of continuous enrollment both before and after the index date. The entire study period was 24 months in duration, including a 12-month pre-index and 12-month post-index period. Three cohorts were identified: 1 that received a medication requiring PA (denied claim, subsequent fill) and 2 nonfilling control groups. Both control groups requested a medication requiring PA, as evidenced by the denied claim, but neither received the medication, either because the medication was not authorized or the member chose not to fill. Claims-based estimates were used to infer whether the individual likely met the criteria for PA, with 1 control group designated as having met the claims-based criteria (qualifying nonfilling cohort) and the other not having done so (nonqualifying nonfilling cohort.) The primary endpoint evaluated was the relationship between PA medication fill status and plan-paid costs (medical [including laboratory] and pharmacy) over the 12-month post-denial period, with generalized linear models adjusting for key covariates including demographics, concomitant medications, pre-index costs, pre-index adherence, and comorbidities. The secondary endpoint of T2DM medication use (post-denial) among the 2 nonfilling control groups was also evaluated.  RESULTS: There were 1,728 members identified who received medication for T2DM requiring PA (the received authorization cohort) and 2,373 who did not (606 qualifying nonfilling cohort; 1,767 nonqualifying nonfilling cohort.) Cohorts were similar with regard to age and gender, but the nonfilling cohort had more comorbidities. Total unadjusted plan-paid 12-month costs were lowest among the received authorization cohort ($11,739), slightly higher ($11,980) for the qualifying nonfilling cohort, and notably higher for the nonqualifying nonfilling cohort ($12,962), although no differences were statistically significant. After adjusting for key covariates, the difference between the nonqualifying nonfilling cohort ($11,980) and the received authorization cohort ($11,729) was statistically significant (P = 0.034). Large differences in plan-paid medical costs ($10,127 for the nonqualifying nonfilling cohort vs. $8,192 for the received authorization cohort) appeared to drive the overall cost totals and were significant in both the unadjusted (P = 0.005) and adjusted models (P less than 0.001). Pharmacy costs were significantly lower for the nonqualifying nonfilling cohort in the adjusted model and for the qualifying nonfilling cohort in both models (all P less than 0.001), but the lower pharmacy costs were not offset by the higher medical costs. In examining the use of medication for treatment of T2DM following the denied claim, 10.6% of the qualifying nonfilling cohort and 13.4% of the nonqualifying nonfilling cohort added another oral therapy, 10.2% and 5.8% added insulin, and 11.9% and 7.1% had treatment intensification, respectively. More than half (56.1%) of the qualifying nonfilling cohort, but only 32.1% of the nonqualifying nonfilling cohort, maintained current therapy.   CONCLUSIONS: This study found higher plan-paid health care costs (overall and medical alone) among members who requested a type 2 diabetes medication requiring PA, but never received it, compared with those who qualified for and received the requested medication. A notable number of individuals who were assumed to have met the criteria based on a claims-based equivalent, but who never received the medication, made no change to their current therapy. Failure of a member to take medication deemed necessary by his or her physician could translate to inadequate control of the diabetic condition and result in an excess of resource utilization and costs for treating the disease and associated comorbidities. In light of the present findings, health plans should consider not only the impact of utilization management strategies on reducing pharmacy costs, but the broader implication for overall health care costs and subsequent treatment patterns among members. 

The cost-effectiveness of exenatide once weekly compared with exenatide twice daily and insulin glargine for the treatment of patients with type two diabetes and body mass index ≥30 kg/m(2) in Spain.

OBJECTIVE: The objective of this analysis was to estimate the cost-effectiveness of exenatide once weekly (EQW) for the treatment of type two diabetes mellitus (T2DM) in Spain. EQW was compared against exenatide twice daily (EBID) and insulin glargine (IG). METHODS: The IMS CORE Diabetes Model was used to project clinical and economic outcomes for patients with T2DM treated with EQW, EBID, and IG. Treatment effects and patient baseline characteristics were taken from the DURATION 3 and pooled DURATION 1 and 5 studies, in the comparison against IG and EBID, respectively. Unit costs and health state utility values were derived from published sources. To reflect diabetes progression, patients started on EQW or EBID, switching to insulin glargine after 3 years. The analysis was conducted from the perspective of the Spanish National Health Service over a time horizon of 35 years with costs and outcomes discounted at 3%. The base case included patients with a BMI > 30 kg/m(2), which is in line with current prescription restrictions in Spain. Uncertainty was addressed through extensive one-way sensitivity analyses around key model parameters and a comprehensive probabilistic sensitivity analysis. RESULTS: When compared with EBID, EQW was the dominant strategy, i.e., less costly and more effective. When compared to IG, the incremental cost-effectiveness ratio was estimated at €12,084 per QALY gained. Sensitivity analysis indicated that the model projections were robust to the various scenarios tested. LIMITATIONS: Primary limitations of the analysis are common to other T2DM analyses and include the extrapolation of short-term clinical data to the 35 year time horizon and uncertainty around optimum treatment durations. CONCLUSION: The analyses indicate that EQW is a cost-effective option for the treatment of T2DM patients in Spain for patients with a BMI > 30 kg/m(2) considering a willingness-to-pay threshold of €30,000 per QALY gained.

Expenditures for medicaid patients treated with exenatide compared with other diabetes management regimens.

OBJECTIVE: To compare Medicaid spending among patients with type 2 diabetes mellitus (T2DM) receiving exenatide or other add-on therapies. STUDY DESIGN: Medicaid data in patients with T2DM were compared among those who initiated exenatide, thiazolidinediones, dipeptidyl peptidase-4 inhibitors, or basal insulin. Patients were on a regimen of metformin and/or sulfonylurea for 30 days and continued the next-line therapy for at least 90 days. METHODS: Total inpatient, outpatient, prescription, and total annual health expenditures were compared for 1 year following treatment initiation. Regression analyses were conducted to compare spending; analyses controlled for patient characteristics, year of initiation, and prior therapy. Propensity score matching was used to match patients receiving exenatide with those receiving other therapies, and analyses were repeated with matched cohorts. RESULTS: Of 23,966 eligible patients, 1345 initiated exenatide and 22,621 initiated other therapies. In the unmatched analysis, medical spending was significantly lower in those given exenatide compared with those given other therapies for inpatient ($1945 vs $3893), prescription ($4505 vs $5714), and total costs ($11,830 vs $15,459) (P <.01 for all); outpatient spending was not significantly different ($5380 vs $5853, P = .15). In the matched analysis (n = 1345 for exenatide, n = 1345 non-exenatide), patients receiving exenatide had significantly lower spending in all 4 categories: inpatient ($1945 vs $4242), outpatient ($5380 vs $6826), prescription ($4505 vs $5878), and total ($11,830 vs $16,945) (P <.01 for all). CONCLUSION: Patients with T2DM receiving exenatide had lower annual Medicaid claims costs compared with patients receiving other therapies.

Willingness to pay for diabetes drug therapy in type 2 diabetes patients: based on LEAD clinical programme results.

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.

Exenatide for once-weekly administration.

▾Exenatide is a glucagon-like peptide 1 (GLP-1) agonist used in the management of people with type 2 diabetes. A twice-daily injectable formulation (▾Byetta - Eli Lilly) was licensed in 2006. ▾Bydureon (Eli Lilly) is a prolonged-release injectable formulation that allows once-weekly administration. Here we discuss the place of Bydureon in the management of type 2 diabetes mellitus.