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.

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.

Cost-effectiveness of exenatide twice daily vs insulin glargine as add-on therapy to oral antidiabetic agents in patients with type 2 diabetes in China.

AIMS: To estimate the long-term cost-effectiveness of exenatide twice daily vs insulin glargine once daily as add-on therapy to oral antidiabetic agents (OADs) for Chinese patients with type 2 diabetes (T2DM). METHODS: The Cardiff Diabetes Model was used to simulate disease progression and estimate the long-term effects of exenatide twice daily vs insulin glargine once daily. Patient profiles and treatment effects required for the model were obtained from literature reviews (English and Chinese databases) and from a meta-analysis of 8 randomized controlled trials comparing exenatide twice daily with insulin glargine once daily add-on to OADs for T2DM in China. Medical expenditure data were collected from 639 patients with T2DM (aged ≥18 years) with and without complications incurred between January 1, 2014 and December 31, 2015 from claims databases in Shandong, China. Costs (2014 Chinese Yuan [¥]) and benefits were estimated, from the payers' perspective, over 40 years at a discount rate of 3%. A series of sensitivity analyses were performed. RESULTS: Patients on exenatide twice daily + OAD had a lower predicted incidence of most cardiovascular and hypoglycaemic events and lower total costs compared with those on insulin glargine once daily + OAD. A greater number of quality-adjusted life years (QALYs; 1.94) at a cost saving of ¥117 706 gained was associated with exenatide twice daily vs insulin glargine once daily. (i.e. cost saving of ¥60 764/QALY) per patient. CONCLUSIONS: In Chinese patients with T2DM inadequately controlled by OADs, exenatide twice daily is a cost-effective add-on therapy alternative to insulin glargine once daily, and may address the problem of an excess of medical needs resulting from weight gain and hypoglycaemia in T2DM treatment.

Treatment patterns in patients with type 2 diabetes mellitus treated with glucagon-like peptide-1 receptor agonists: Higher adherence and persistence with dulaglutide compared with once-weekly exenatide and liraglutide.

AIMS: To compare adherence (proportion of days covered [PDC]), persistence, and treatment patterns among patients with type 2 diabetes mellitus (T2DM) newly initiating glucagon-like peptide-1 receptor agonists (GLP-1RAs). More specifically, the main objectives were to compare dulaglutide vs exenatide once weekly and dulaglutide vs liraglutide. METHODS: Patients with T2DM newly initiating dulaglutide, albiglutide, exenatide once weekly, exenatide twice daily and liraglutide between November 2014 and April 2015 were hierarchically selected from Truven Health's MarketScan Research Databases. Propensity score matching was used to account for selection bias. Adherence to and persistence with the index GLP-1RA, and switching and augmentation patterns were assessed during the 6-month post-index period. RESULTS: Mean adherence for the matched cohorts was significantly higher for dulaglutide than for exenatide once weekly (0.72 vs 0.61; P < .0001) and liraglutide (0.71 vs 0.67; P < .0001). The percentage of patients achieving PDC ≥ 0.80 was significantly higher for dulaglutide compared with exenatide once weekly (54.2% vs 37.9%; P < .0001) and liraglutide (53.5% vs 44.3%; P < .0001). The mean (standard deviation) days on treatment for all matched patients was significantly higher for patients in the dulaglutide cohort compared with those in the exenatide once-weekly (148.4 [55.4] vs 123.6 [61.6]; P < .0001) and liraglutide cohorts (146.0 [56.9] vs 137.4 [60.1]; P < .0001). A significantly lower proportion of patients on dulaglutide discontinued treatment compared with those on exenatide once weekly (26.2% vs 48.4%; P < .0001) and those on liraglutide (28.0% vs 35.6%; P < .0001). CONCLUSIONS: Dulaglutide initiators had significantly higher adherence, were more persistent, and had lower discontinuation rates compared with initiators of exenatide once weekly or liraglutide during the 6-month follow-up period.

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 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.

Retrospective study comparing healthcare costs and utilization between commercially insured patients with type 2 diabetes mellitus who are newly initiating exenatide once weekly or liraglutide in the United States.

OBJECTIVE: To compare healthcare costs and utilization between commercially insured patients with type 2 diabetes mellitus (T2DM) in the United States newly initiating exenatide once weekly (QW) or liraglutide. METHODS: This retrospective cohort study used US administrative claims data to study patients with T2DM initiating exenatide QW or liraglutide (initiated therapy = index therapy). Patients were included if they had T2DM, were glucagon-like peptide-1 receptor agonist (GLP-1RA) naïve, initiated exenatide QW or liraglutide from 1 February 2012 to 1 October 2012 (date of initiation = index), were ≥18 years at index, and had continuous enrollment for 12 months before (baseline) to 6 months after index (follow-up). Study outcomes were overall and diabetes-specific healthcare utilization and costs. Multivariable regressions compared the study outcomes between exenatide QW and liraglutide, adjusting for potential confounders. Sensitivity analyses were performed to assess liraglutide by dose (1.2 mg/1.8 mg). RESULTS: The study sample included 9106 liraglutide (4188, 1.2 mg; 4918, 1.8 mg) patients and 2445 exenatide QW patients. In multivariable-adjusted analyses, compared with liraglutide patients, exenatide QW patients had statistically significantly lower odds of overall inpatient admissions (odds ratio [OR] = 0.80, p = 0.046) and diabetes-specific (OR = 0.83, p = 0.026) inpatient admissions, similar overall total costs ($7833 exenatide QW, $8296 liraglutide, p = 0.069) and diabetes-specific total costs ($3610 exenatide QW, $3736 liraglutide, p = 0.298), and statistically significantly lower overall medical costs ($3939 exenatide QW, $4652 liraglutide, p = 0.008) and diabetes-specific medical costs ($1161 exenatide QW, $1469 liraglutide, p = 0.007). Sensitivity analyses assessing liraglutide by dose were directionally consistent. Unadjusted exploratory analyses showed that exenatide QW patients obtained a greater median number of days supplied for their GLP-1RA during follow-up (141 days) than liraglutide patients (124 days). CONCLUSIONS: In this 6 month follow-up study, patients receiving exenatide QW had similar total healthcare costs but lower odds of inpatient admission and lower medical costs compared with patients receiving liraglutide.

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.

Target-mediated pharmacokinetic/pharmacodynamic model based meta-analysis and dosing regimen optimization of a long-acting release formulation of exenatide in patients with type 2 diabetes mellitus.

A hybrid pharmacokinetic/pharmacodynamic (PK/PD) model with extended-release (ER) process and target mediated drug disposition (TMDD) was developed for exenatide ER to account for its complex absorption process and glucagon-like peptide 1 receptor (GLP-1R)-mediated non-linear PK behaviors along with its influences to fasting plasma glucose (FPG) and hemoglobin A1c (HbA1c). Using hybrid PK/PD model, simulations were done to explore the potential dosing regimens which could achieve likelihood of more pharmacodynamic exposure with respect to FPG and HbA1c over a much shorter period compared with the currently used treatment protocol. The mean PK/PD data about exenatide ER for type 2 diabetes mellitus (T2DM) were digitized from the publications, and the hybrid PK/PD model was performed using the Monolix 4.3 program. The plasma concentration-time and FPG/HbA1c-time profiles for exenatide ER subcutaneously administrated to patients with T2DM were well described by this hybrid model. Monte Carlo simulation was applied to mimic the PK profiles when higher loading dose 7.5 and 5.0 mg exenatide ER were subcutaneously administrated with different dosing intervals at the first 3 weeks of 30-week treatment. Two potentially optimizing schedules could improve the likelihood of achieving much more FPG and HbA1c exposures than currently used clinical treatment protocol.

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.

[Bydureon: first once weekly GLP-1 receptor agonist (exenatide LAR)]. / Le médicament du mois. Bydureon: premier agoniste des récepteurs du GLP-1 en une injection hebdomadaire (exénatide à libération prolongée).

Bydureon is a new galenic formulation (long-acting release) of exenatide, the first agonist of Glucagon-Like Peptide-1 (GLP-1) receptors having been commercialized for the management of type 2 diabetes. The microsphere technology permits a prolonged absorption of exenatide from the subcutaneous depot, which allows one injection per week instead of two injections per day with the initial formulation of exenatide (Byetta). The clinical development programme DURATION showed that exenatide 2 mg once weekly more markedly reduces glycated haemoglobin (HbA(1c)), with a similar weight loss but a better digestive tolerance profile (less nausea and vomiting after treatment initiation), compared with the twice daily 10 microg exenatide. When compared to other glucose-lowering agents, once weekly exenatide is more efficacious than sitagliptin, pioglitazone or basal insulin (glargine or detemir), with the advantage of producing weight loss and lowering arterial blood pressure. It does not induce hypoglycaemia and does not necessarily require home blood glucose monitoring, two advantages compared with insulin therapy. Bydureon is currently only reimbursed in Belgium after failure of and in addition to metformin-sulfonylurea combination.

Exenatide twice daily: a review of its use in the management of patients with type 2 diabetes mellitus.

Exenatide, administered subcutaneously twice daily (Byetta(®)), is a synthetic version of the natural peptide exendin-4, which is a glucagon-like peptide-1 (GLP-1) receptor agonist (incretin mimetic). Exenatide binds to the GLP-1 receptor with the same affinity as GLP-1, but has a much longer half-life, since it is not degraded by the enzyme dipeptidyl peptidase-4. Exenatide twice daily enhances glucose-dependent insulin secretion, suppresses inappropriately elevated glucagon secretion, slows gastric emptying and reduces caloric intake. In well-designed clinical trials, adjunctive subcutaneous exenatide 5 or 10 µg twice daily for 16-52 weeks significantly and dose-dependently improved glycaemic control and reduced mean body weight compared with placebo in patients with type 2 diabetes inadequately controlled with oral antihyperglycaemic drugs (OADs) and/or basal insulin. The improvements in glycaemic control and reductions in body weight were stably maintained during long-term therapy (up to 3.5 years). The efficacy of adjunctive exenatide twice daily was generally similar to that of basal, prandial or biphasic insulin, sulfonylureas, rosiglitazone and lixisenatide, and less than that of liraglutide, taspoglutide or exenatide once weekly with respect to reductions in glycated haemoglobin. Exenatide twice daily was generally well tolerated; mild to moderate nausea and vomiting, which decreased with time on therapy, were the most common adverse events. In patients not receiving concomitant sulfonylureas or insulin, the incidence of hypoglycaemia was low; when it did occur, it was generally mild in severity. Thus, adjunctive exenatide twice daily is a valuable option in the treatment of type 2 diabetes inadequately controlled with OADs and/or basal insulin.

Patient-reported outcomes among patients using exenatide twice daily or insulin in clinical practice in six European countries: the CHOICE prospective observational study.

BACKGROUND: Improvements in the clinical condition of patients with type 2 diabetes are often accompanied by improvements in health-related quality of life and other patient-reported outcomes (PROs), but data assessing injectable treatment initiation from the patient's perspective in routine clinical practice are lacking. We examined PROs in patients initiating injectable treatment in the CHOICE (CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy) study. METHODS: CHOICE was a 24-month, prospective observational study conducted in six European countries. Patients initiated exenatide twice daily (BID) or insulin based on a physician's clinical judgement. Clinical and PRO data were collected at baseline (injectable therapy initiation) and after approximately 3, 6, 12, 18 and 24 months. The two treatment cohorts had different baseline characteristics; therefore, no statistical comparisons of endpoints between main cohorts were conducted. RESULTS: There were 2388 patients eligible for analysis (exenatide BID cohort, n = 1114; insulin cohort, n = 1274). Mean positive changes in Impact of Weight on Quality of Life-Lite (IWQOL-Lite) total score and EuroQoL5-Dimension (EQ-5D) index and visual analogue scale (VAS) scores were observed in both cohorts with most changes observed during the first 6 months after injectable therapy initiation. Patients who experienced weight loss (≥ 1 kg) at 24 months appeared to have higher mean improvements in IWQOL-Lite total score than did patients with weight gain or no weight change. Patients who met the composite clinical endpoint of glycated haemoglobin (HbA1c) <7.0%, no weight gain (≤ 1 kg) and no hypoglycaemia generally experienced higher mean improvements in EQ-5D index and VAS scores (compared with patients who did not meet this endpoint) and Diabetes Health Profile-18 scores (versus the main cohorts). High levels of missing data were observed for all PRO measures in both cohorts compared with those for clinical outcomes. CONCLUSIONS: These data from a clinical practice study support those from clinical trials, suggesting that PROs are not adversely affected, and may be improved, by injectable therapy initiation. PRO data may aid appropriate treatment selection for individual patients. TRIAL REGISTRATION: ClinicalTrials.gov, NCT00635492.

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 real-world adherence in patients with type 2 diabetes initiating once-daily liraglutide 1.8 mg or twice-daily exenatide 10 µg.

BACKGROUND: The effectiveness of a drug is significantly influenced by a patient's adherence to the required regimen. OBJECTIVE: The goal of this retrospective database analysis was to determine the factors affecting adherence over a 12-month follow-up period in adults with type 2 diabetes mellitus (DM) initiating once-daily liraglutide (1.8 mg) or twice-daily exenatide (10 µg). METHODS: A patient-centric claims database was used, covering the period January 2009 to December 2011. Patients were included if they had ≥1 claim of once-daily liraglutide 1.8 mg or twice-daily exenatide 10 µg from January to December 2010 (index date [ID]), ≥2 diagnoses of type 2 DM before ID, continuous enrollment for 12 months before and after ID, and age ≥18 years at ID. Patients were required to be glucagon-like peptide-1 receptor agonist treatment-naive in the 12 months preceding ID and have a second prescription for once-daily liraglutide 1.8 mg or twice-daily exenatide 10 µg during the 12 months after ID. The medication possession ratio (MPR) was used as a continuous variable and to categorize patients as high-adherent (MPR ≥80%) or low-adherent (MPR <80%). Regression analyses were conducted to determine the predictors for nonadherence in the type 2 DM population, with bivariate testing of the MPR categories conducted initially to determine the predictors to be included in the final regression model. RESULTS: A total of 3623 patients (once-daily liraglutide 1.8 mg, n = 2036; twice-daily exenatide 10 µg, n = 1587) were identified. Variables found to reduce adherence were younger age, female sex, Southern geographic region, twice-daily exenatide treatment, and higher percentage of copayment from the claimant. After adjusting for confounding factors, patients receiving once-daily liraglutide 1.8 mg were ∼11% more adherent than patients receiving twice-daily exenatide 10 µg (95% CI, 7-14; P < 0.0001). The odds ratio for "poor" adherence (MPR <80%) with twice-daily exenatide 10 µg therapy compared with liraglutide 1.8 mg once-daily was 1.33 (95% CI, 1.16-1.53; P < 0.0001). CONCLUSIONS: This study found that adherence to once-daily liraglutide 1.8 mg treatment was superior to twice-daily exenatide 10 µg over a 12-month follow-up period. Nonadherence has important implications to the health care system, both in terms of clinical effectiveness and economic burden (eg, hospitalization, productivity losses). Using strategies to increase adherence is vital to reduce the future clinical and economic burden of diabetes.

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.

Acute peripheral GLP-1 receptor agonism or antagonism does not alter energy expenditure in rats after Roux-en-Y gastric bypass.

Compared to traditional weight loss strategies, the compensatory decrease in energy expenditure in response to body weight loss is markedly attenuated after Roux-en-Y gastric bypass surgery (RYGB). Because basal and postprandial levels of glucagon-like peptide-1 (GLP-1) are increased after RYGB surgery, and because GLP-1 has been shown to increase energy expenditure, we investigated if increased GLP-1 levels are involved in the alterations in energy expenditure after RYGB. Adult male Wistar rats were randomized for RYGB (n=8) or sham surgery (n=17). Part of the sham-operated rats were food restricted and body weight-matched (n=8) to the RYGB animals. The effects of acute subcutaneous administration of the GLP-1 antagonist Exendin (9-39) (Ex-9, 30µg/kg) or the GLP-1 agonist Exendin-4 (Ex-4, 5µg/kg), respectively, on energy expenditure were tested using indirect calorimetry. We found that Ex-9 increased food intake in RYGB, but not in sham-operated rats. Energy expenditure was lower in RYGB and sham-operated body weight-matched rats compared to sham-operated ad libitum fed rats, but significantly higher in RYGB rats compared to sham-operated body weight-matched rats. There was no effect of Ex-9 treatment on energy expenditure in either group of animals. Similarly, Ex-4 decreased food intake more in RYGB than in sham-operated rats, but Ex-4 did not modulate energy expenditure in any surgical group. We conclude that acute modulation of GLP-1 signaling is not directly involved in altered energy expenditure after RYGB surgery in rats.

Exenatide therapy and the risk of pancreatitis and pancreatic cancer in a privately insured population.

BACKGROUND: Postmarketing reports have linked exenatide use with acute pancreatitis and pancreatic cancer, but a definitive relationship has yet to be established. SUBJECTS AND METHODS: We conducted a retrospective cohort analysis of patients with type 2 diabetes with employer-provided health insurance from 2007 to 2009. Multivariate models estimated the association between exenatide use and acute pancreatitis and pancreatic cancer. We required at least 1 year of exenatide exposure in the pancreatic cancer analysis. Sensitivity analyses were conducted that quasirandomized exenatide use based on patient out-of-pocket costs. RESULTS: Among 268,561 patients included in the acute pancreatitis analysis, only 2.6% used exenatide. Hospitalization for acute pancreatitis was rare (0.247% of patients). In unadjusted and adjusted analyses, patients who did not use exenatide were more likely to be hospitalized for acute pancreatitis (0.249% vs. 0.196% in unadjusted analysis), but the difference was not statistically significant in either analysis (P = 0.22 and P = 0.70, respectively). Among 209,306 patients in the pancreatic cancer analysis, 0.070% were diagnosed with pancreatic cancer, and 0.88% had at least 1 year of continuous exenatide exposure prior to the diagnosis. Those with exenatide exposure had higher rates of pancreatic cancer compared with those without (0.081% vs. 0.070% in unadjusted analysis). In both unadjusted and adjusted analyses, the difference was not statistically significant (P = 0.80 and P = 0.46, respectively). In sensitivity analyses, results were similar. CONCLUSIONS: We found no association between exenatide use and either hospitalization for acute pancreatitis or pancreatic cancer in a large sample of privately insured U.S. patients.