Cost-effectiveness of GLP-1 receptor agonists versus insulin for the treatment of type 2 diabetes: a real-world study and systematic review.

BACKGROUND: To conduct a real-word-study-based cost-effectiveness analysis of a GLP-1 receptor agonist (GLP-1RA) versus insulin among type 2 diabetes patients requiring intensified injection therapy and a systematic review of cost-effectiveness studies of GLP-1RAs versus insulin. METHODS: Individual-level analyses incorporating real-world effectiveness and cost data were conducted for a cohort of 1022 propensity-score-matched pairs of GLP-1RA and insulin users from Taiwan's National Health Insurance Research Database, 2007-2016. Study outcomes included the number needed to treat (NNT) to prevent one case of clinical events, healthcare costs, and cost per case of event prevented. Costs were in 2019 US dollars. Analyses were performed from a third-party payer and healthcare sector perspectives. Structured systematic review procedures were conducted to synthesize updated evidence on the cost-effectiveness of GLP-1RAs versus insulin. RESULTS: Over a mean follow-up of 2.3 years, the NNT using a GLP-1RA versus insulin to prevent one case of all-cause mortality and hospitalized hypoglycemia was 57 and 30, respectively. Using GLP-1RAs instead of insulin cost US$54,851 and US$29,115 per case of all-cause mortality and hospitalized hypoglycemia prevented, respectively, from the payer perspective, and saved US$19,391 and US$10,293, respectively, from the healthcare sector perspective. Sensitivity analyses showed that the probability of using GLP-1RAs versus insulin being cost-effective for preventing one case of all-cause mortality or hospitalized hypoglycemia ranged from 60 to 100%. The systematic review revealed a cost-effective profile of using GLP-1RAs versus insulin. CONCLUSIONS: Using GLP-1RAs versus insulin for type 2 diabetes patients requiring intensified injection therapy in clinical practice is cost-effective.

Drug-class-specific changes in the volume and cost of antidiabetic medications in Poland between 2012 and 2015.

AIM: to investigate the drug-class-specific changes in the volume and cost of antidiabetic medications in Poland in 2012-2015. METHODS: This retrospective analysis was conducted based on the National Health Fund database covering an entire Polish population. The volume of antidiabetic medications is reported according to ATC/DDD methodology, costs-in current international dollars, based on purchasing power parity. RESULTS: During a 4-year observational period the number of patients, consumption of antidiabetic drugs and costs increased by 17%, 21% and 20%, respectively. Biguanides are the basic diabetes medication with a 39% market share. The insulin market is still dominated by human insulins, new antidiabetics (incretins, thiazolidinediones) are practically absent. Insulins had the largest share in diabetes medications expenditures (67% in 2015). The increase in antidiabetic medications costs over the analysed period of time was mainly caused by the increased use of insulin analogues. CONCLUSIONS: The observed tendencies correspond to the evidence-based HTA recommendations. The reimbursement status, the ratio of cost to clinical outcomes and data on the long-term safety have a deciding impact on how a drug is used.

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.

SGLT2 inhibitors or GLP-1 receptor agonists as second-line therapy in type 2 diabetes: patient selection and perspectives.

Controversy exists regarding the selection of second-line therapy for patients with type 2 diabetes mellitus (T2DM) who are unable to achieve glycemic control with metformin therapy alone. Newer pharmacologic treatments for T2DM include glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors. Both the classes of medication are efficacious, exhibit positive effects on weight, and are associated with minimal risk of hypoglycemia. The purpose of this review is to compare the clinical trial and real-world effectiveness data of glucagon-like peptide-1 receptor agonists versus sodium-glucose cotransporter 2 inhibitors related to A1c reduction, weight loss, cost-effectiveness, cardiovascular outcomes, and safety in patients with T2DM. This review summarizes comparative evidence for providers who are determining which of the two classes may be the most appropriate for a specific patient.

Regional variation in use of a new class of antidiabetic medication among medicare beneficiaries: the case of incretin mimetics.

BACKGROUND: When incretin mimetic (IM) medications were introduced in 2005, their effectiveness compared with other less-expensive second-line diabetes therapies was unknown, especially for older adults. Physicians likely had some uncertainty about the role of IMs in the diabetes treatment armamentarium. Regional variation in uptake of IMs may be a marker of such uncertainty. OBJECTIVE: To investigate the extent of regional variation in the use of IMs among beneficiaries and estimate the cost implications for Medicare. METHODS: This was a cross-sectional analysis of 2009-2010 claims data from a nationally representative sample of 238 499 Medicare Part D beneficiaries aged ≥65 years, who were continuously enrolled in fee-for-service Medicare and Part D and filled ≥1 antidiabetic prescription. Beneficiaries were assigned to 1 of 306 hospital-referral regions (HRRs) using ZIP codes. The main outcome was adjusted proportion of antidiabetic users in an HRR receiving an IM. RESULTS: Overall, 29 933 beneficiaries (12.6%) filled an IM prescription, including 26 939 (11.3%) for sitagliptin or saxagliptin and 3718 (1.6%) for exenatide or liraglutide. The adjusted proportion of beneficiaries using IMs varied more than 3-fold across HRRs, from 5th and 95th percentiles of 5.2% to 17.0%. Compared with non-IM users, IM users faced a 155% higher annual Part D plan ($1067 vs $418) and 144% higher patient ($369 vs $151) costs for antidiabetic prescriptions. CONCLUSION: Among older Part D beneficiaries using antidiabetic drugs, substantial regional variation exists in the use of IMs, not accounted for by sociodemographics and health status. IM use was associated with substantially greater costs for Part D plans and beneficiaries.

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.

Incretin-based therapies in the management of type 2 diabetes: rationale and reality in a managed care setting.

In addition to the hypoglycemia and weight gain associated with many treatments for type 2 diabetes, alpha-glucosidase inhibitors, thiazolidinediones, metformin, sulfonylureas, and the glinides do not address all of the multiple defects existing in the pathophysiology of the disease. Cumulatively, these oral agents address the influx of glucose from the gastrointestinal tract, impaired insulin activity, and acute beta-cell dysfunction in type 2 diabetes; however, until recently, there were no means to deal with the inappropriate hyperglucagonemia or chronic beta-cell-decline characteristic of the disease. The recently introduced incretin-based therapies serve to address some of the challenges associated with traditionally available oral antidiabetic agents. In addition to improving beta-cell function, stimulating insulin secretion, and inhibiting glucagon secretion, these agents reduce appetite, thereby stabilizing weight and/or promoting weight loss in patients with type 2 diabetes. Of the incretin-based therapies, both the dipeptidyl peptidase-4 (DPP-4) inhibitors and the glucagon-like peptide-1 (GLP-1) receptor agonists stimulate insulin secretion and inhibit glucagon secretion. The subsequent review outlines evidence from selected clinical trials of the currently available GLP-1 receptor agonists, exenatide and liraglutide, and DPP-4 inhibitors, sitagliptin and saxagliptin. Earlier and more frequent use of these incretin-based therapies is recommended in the treatment of type 2 diabetes, based on their overall safety and ability to achieve the glycosylated hemoglobin level goal. As such, both the American Diabetes Association and the American Association of Clinical Endocrinologists/American College of Endocrinology (AACE/ACE) treatment algorithms recommend the use of incretin-based therapy in both treatment-naive and previously treated patients. The AACE/ACE guidelines clearly state that these agents should not be limited to third- or fourth-line therapy.

Part D coverage gap and adherence to diabetes medications.

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.

Incretin-based therapy: how do incretin mimetics and DPP-4 inhibitors fit into treatment algorithms for type 2 diabetic patients?

Incretin-based antidiabetic medications have been approved for clinical use for approximately two to three years. While their major clinical characteristics have been known from clinical trials, the discussion now focuses on the best clinical use of GLP-1 receptor agonists (incretin mimetics) and inhibitors of the protease dipeptidyl peptidase-4 (DPP-4). Any novel drug will not fully disclose its spectrum of beneficial and adverse activity before long-term trials with clinical endpoints are available. This, typically, will last 5-8 years. Nevertheless, there are convincing reasons to use incretin mimetics and DPP-4 inhibitors even in the absence of such results. This decision should be based on specific patient characteristics and (expected) treatment results, in comparison to other available treatment options. The present manuscript tries to describe the current state-of-the-art of using incretin mimetics and DPP-4 inhibitors in clinical practice, including an attempt to suggest their place in treatment algorithms for type 2-diabetic patients.