Cost saving analysis of prediabetes intervention modalities in comparison with inaction using Markov state transition model-A multiregional case study.

BACKGROUND: Prediabetes management is a priority for policymakers globally, to avoid/delay type 2 diabetes (T2D) and reduce severe, costly health consequences. Countries moving from low to middle income are most at risk from the T2D "epidemic" and may find implementing preventative measures challenging; yet prevention has largely been evaluated in developed countries. METHODS: Markov cohort simulations explored costs and benefits of various prediabetes management approaches, expressed as "savings" to the public health care system, for three countries with high prediabetes prevalence and contrasting economic status (Poland, Saudi Arabia, Vietnam). Two scenarios were compared up to 15 y: "inaction" (no prediabetes intervention) and "intervention" with metformin extended release (ER), intensive lifestyle change (ILC), ILC with metformin (ER), or ILC with metformin (ER) "titration." RESULTS: T2D was the highest-cost health state at all time horizons due to resource use, and inaction produced the highest T2D costs, ranging from 9% to 34% of total health care resource costs. All interventions reduced T2D versus inaction, the most effective being ILC + metformin (ER) "titration" (39% reduction at 5 y). Metformin (ER) was the only strategy that produced net saving across the time horizon; however, relative total health care system costs of other interventions vs inaction declined over time up to 15 y. Viet Nam was most sensitive to cost and parameter changes via a one-way sensitivity analysis. CONCLUSIONS: Metformin (ER) and lifestyle interventions for prediabetes offer promise for reducing T2D incidence. Metformin (ER) could reduce T2D patient numbers and health care costs, given concerns regarding adherence in the context of funding/reimbursement challenges for lifestyle interventions.

Analysis of pharmacoeconomic value of sitagliptin in the treatment of diabetes mellitus.

OBJECTIVE: Diabetes mellitus is a chronic metabolic disease which has an adverse impact on the quality of patient's life, so patients often need to receive treatment for a long time. Selection of medications with high therapeutics effects and low cost is very important for patients to take medicine for a longer period of time. Sitagliptin is a drug which is widely used in clinics and can effectively control blood glucose level. This article explores the pharmacoeconomic value of Sitagliptin in the treatment of diabetes mellitus. PATIENTS AND METHODS: A total of 100 patients with diabetes mellitus treated were recruited in this study. The patients were randomly divided into 4 groups with 25 cases in each group. Patients in group A were treated with pioglitazone, group B with Sitagliptin, group C with metformin and group D with glimepiride. The cost of the drugs, the treatment results and adverse effects were compared. RESULTS: Compared with group A, C and D, the cost-effectiveness ratio of group B was low (p<0.05), and the therapeutic effect was high (p<0.05). In addition, the incidence of adverse reactions in group B was lower than that in group A, C and D (p<0.05). There was no significant difference in the levels of FPG, 2hPG and HbAlc in patients among the four groups before treatment (p>0.05). After treatment, the levels of FPG, 2hPG and HbAlc in group B were significantly lower than those in groups A, C and D (p<0.05). Finally, there was no significant difference in waist circumference and BMI among the four groups before treatment (p>0.05). After treatment, the waist circumference and BMI in group B were lower than those in groups A, C and D (p<0.05). CONCLUSIONS: The application of Sitagliptin in the treatment of diabetic patients can effectively enhance the therapeutic effect. The cost effectiveness is satisfactory, and the blood glucose level can be maintained at a stable state.

Cost-Effectiveness of Dipeptidylpeptidase-4 Inhibitors Added to Metformin in Patients With Type 2 Diabetes in China.

Purpose: Dipeptidylpeptidase-4 (DPP-4) inhibitors, including linagliptin, alogliptin, saxagliptin, sitagliptin, and vildagliptin, are used for the treatment of type 2 diabetes mellitus (T2DM) patients in China. This study assessed the economic outcomes of different DPP-4 inhibitors in patients with T2DM inadequately controlled with metformin in the Chinese context. Materials and Methods: In this study, the validated Chinese Outcomes Model for T2DM (COMT) was conducted to project economic outcomes from the perspective of Chinese healthcare service providers. Efficacy and safety, medical expenditure, and utility data were derived from the literature, which were assigned to model variables. The primary outputs of the model included the lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratio (ICER). One-way and probability sensitivity analysis was conducted to assess the potential uncertainties of parameters. Results: Of the five competing strategies, alogliptin 25 mg strategy yielded the most significant health outcome, which associated with improvements in discounted QALY of 0.007, 0.014, 0.011, and 0.022 versus linagliptin 5 mg, saxagliptin 5 mg, sitagliptin 100 mg and vildagliptin50 mg, respectively. The sitagliptin 100 mg strategy was the cheapest option. The ICER of alogliptin 25 mg against sitagliptin 100 mg strategy was $6,952 per additional QALY gained, and the rest of the strategies were dominated or extended dominated. The most influential parameters were the cost of DPP-4 inhibitors and their treatment efficacy. Conclusions: These results suggested that alogliptin was a preferred treatment option compared with other DPP-4 inhibitors for Chinese patients whose T2DM are inadequately controlled on metformin monotherapy.

Pharmacoeconomic Analysis of Sitagliptin/Metformin for the Treatment of Type 2 Diabetes Mellitus: A Cost-Effectiveness Study.

OBJECTIVES: To assess the cost-effectiveness and cost utility of sitagliptin/metformin for the treatment of type 2 diabetes mellitus compared to those of glibenclamide/metformin in a semiprivate hospital and to compare the cost-effectiveness and cost utility of sitagliptin/metformin in a semiprivate hospital to those in the public health system (PHS) of Ecuador in 2019. METHODS: A cost-effectiveness study considering the probability of cardiovascular death as the outcome and quality-adjusted life-year as a measure of utility, estimating direct medical costs in US dollars by a model case from the perspective of the third payer. The results will be presented as an incremental cost-effectiveness ratio. One-way and 2-way sensitivity analyses with tornado diagrams were performed. RESULTS: Direct medical costs were lower at the hospital than from the PHS in Ecuador. Considering the drugs metformin/sitagliptin, the total cost was $35.69 less in the hospital ($880.38) than from the comparator ($916.07). The highest percentage of direct medical costs corresponded to drugs (between 63.94% and 84.65%). An ICER of -$19 131.61 was obtained at the Hospital Un Canto a la Vida and -$1621.85 at PHS. In addition, the cost per quality-adjusted life-year earned was $611.11. Sensitivity analysis showed that the probability of drug use and the relative risk of cardiovascular death associated with such prescription were parameters that most affected the model. CONCLUSIONS: The combination therapy metformin/sitagliptin compared to metformin/glibenclamide was shown not to be cost-effective in the Hospital Un Canto a la Vida, and highly cost-effective in the PHS.

Targeting of the diabetes prevention program leads to substantial benefits when capacity is constrained.

OBJECTIVE: Approximately 84 million people in the USA have pre-diabetes, but only a fraction of them receive proven effective therapies to prevent type 2 diabetes. We estimated the value of prioritizing individuals at highest risk of progression to diabetes for treatment, compared to non-targeted treatment of individuals meeting inclusion criteria for the Diabetes Prevention Program (DPP). METHODS: Using microsimulation to project outcomes in the DPP trial population, we compared two interventions to usual care: (1) lifestyle modification and (2) metformin administration. For each intervention, we compared targeted and non-targeted strategies, assuming either limited or unlimited program capacity. We modeled the individualized risk of developing diabetes and projected diabetic outcomes to yield lifetime costs and quality-adjusted life expectancy, from which we estimated net monetary benefits (NMB) for both lifestyle and metformin versus usual care. RESULTS: Compared to usual care, lifestyle modification conferred positive benefits and reduced lifetime costs for all eligible individuals. Metformin's NMB was negative for the lowest population risk quintile. By avoiding use when costs outweighed benefits, targeted administration of metformin conferred a benefit of $500 per person. If only 20% of the population could receive treatment, when prioritizing individuals based on diabetes risk, rather than treating a 20% random sample, the difference in NMB ranged from $14,000 to $20,000 per person. CONCLUSIONS: Targeting active diabetes prevention to patients at highest risk could improve health outcomes and reduce costs compared to providing the same intervention to a similar number of patients with pre-diabetes without targeted selection.

Cost-effectiveness analysis of polycystic ovary syndrome management and the risk of gestational diabetes in pregnant women: a decision-tree model.

BACKGROUND: This study estimated the cost-effectiveness of metformin to reduce the risk of gestational diabetes mellitus (GDM) in pregnant women with polycystic ovary syndrome (PCOS) from the US health-care payer perspective. METHODS: A decision tree was developed to simulate the progression of PCOS in a hypothetical cohort of 10,000 pregnant women diagnosed with PCOS and two scenarios were tested. Normal glucose regulation without developing GDM, average cost-effectiveness ratios (ACER), and the incremental cost-effectiveness ratios (ICERs) were the outcome measures assessed through pregnancy. Evidence from randomized clinical trials and other published literature were used to assess disease progression and its associated health-care costs. Sensitivity analyses that varied key model parameters were conducted. RESULTS: Management of PCOS with metformin was associated with lowest ACER ($669.78 per normal glucose regulation without GDM) as compared to 'no intervention' strategy. Metformin use is the most cost-effective strategy to manage PCOS during pregnancy with average cost savings of $7,593,372.97 and an average effect gain of 2271 of normal glucose regulation without GDM among pregnant women with PCOS. Sensitivity analyses determined that the results are robust. CONCLUSIONS: Management of PCOS during pregnancy may be a cost-effective strategy to reduce GDM risk and its associated complications.

Metformin Should Not Be Used to Treat Prediabetes.

Based on the results of the Diabetes Prevention Program Outcomes Study (DPPOS), in which metformin significantly decreased the development of diabetes in individuals with baseline fasting plasma glucose (FPG) concentrations of 110-125 vs. 100-109 mg/dL (6.1-6.9 vs. 5.6-6.0 mmol/L) and A1C levels 6.0-6.4% (42-46 mmol/mol) vs. <6.0% and in women with a history of gestational diabetes mellitus, it has been suggested that metformin should be used to treat people with prediabetes. Since the association between prediabetes and cardiovascular disease is due to the associated nonglycemic risk factors in people with prediabetes, not to the slightly increased glycemia, the only reason to treat with metformin is to delay or prevent the development of diabetes. There are three reasons not to do so. First, approximately two-thirds of people with prediabetes do not develop diabetes, even after many years. Second, approximately one-third of people with prediabetes return to normal glucose regulation. Third, people who meet the glycemic criteria for prediabetes are not at risk for the microvascular complications of diabetes and thus metformin treatment will not affect this important outcome. Why put people who are not at risk for the microvascular complications of diabetes on a drug (possibly for the rest of their lives) that has no immediate advantage except to lower subdiabetes glycemia to even lower levels? Rather, individuals at the highest risk for developing diabetes-i.e., those with FPG concentrations of 110-125 mg/dL (6.1-6.9 mmol/L) or A1C levels of 6.0-6.4% (42-46 mmol/mol) or women with a history of gestational diabetes mellitus-should be followed closely and metformin immediately introduced only when they are diagnosed with diabetes.

Cost-utility analysis of second-line anti-diabetic therapy in patients with type 2 diabetes mellitus inadequately controlled on metformin.

BACKGROUND: There are significant differences in costs and effectiveness among the second-line treatment options for type 2 diabetes (T2DM). We aimed to evaluate the cost-effectiveness of the second-line anti-diabetic therapy in T2DM patients inadequately controlled on metformin (MET) in Taiwan from the perspective of the National Health Insurance (NHI). METHODS: The Cardiff T2DM model was used to predict the occurrence of mortality, diabetes-related complications, and drug adverse events. Five second-line treatments were selected for the analysis: sodium-glucose cotransporter 2 inhibitors (SGLT-2-i), glucagon-like peptide-1 receptor agonists (GLP-1-RA), dipeptidyl peptidase-4 inhibitor (DPP-4-i), sulfonylurea (SU), and insulin (INS). Treatment efficacy data were obtained from meta-analyses and randomized clinical trials, whereas cost data were derived from the NHI databases. RESULTS: The analysis found that SU + MET (DPP-4-i as triple therapy) had the lowest cost, and SU + MET (SGLT-2-i as triple therapy) was associated with a mean incremental benefit of 0.47 quality-adjusted life years (QALYs) at an incremental cost of NT$2769, resulting in an incremental cost-effectiveness ratio (ICER) of NT$5840/QALY. Compared to their next less costly strategies, SGLT-2-i + MET (SU as triple therapy) and SGLT-2-i + MET (DPP-4-i as triple therapy) had ICER values of NT$63,170/QALY and NT$64,090/QALY, respectively. These results were fairly robust to extensive sensitivity analyses, but were relatively sensitive to baseline HbA1c, HbA1c threshold, and utilities. CONCLUSION: The addition of either SU or SGLT-2-i to MET was found to be cost-effective, using the 2019 forecast for GDP per capita of Taiwan (NT$770,770) as the willingness to pay (WTP) threshold.

Budget impact analysis for dapagliflozin in type 2 diabetes in Egypt.

Introduction: Type 2 diabetes mellitus (T2DM) is a major health problem in Egypt with a high impact on morbidity, mortality, and healthcare resources. This study evaluated the budget impact and the long-term consequences of dapagliflozin versus other conventional medications, as monotherapy, from both the societal and health insurance perspectives in Egypt.Methods: A static budget impact model was developed to estimate the financial consequences of adopting dapagliflozin on the healthcare payer budget. We measured the direct medical costs of dapagliflozin (new scenario) as monotherapy, compared to metformin, insulin, sulphonylurea, dipeptidyl peptidase-4 (DPP-4) inhibitors, thiazolidinedione, and repaglinide (old scenarios) over a time horizon of 3 years. Myocardial infarction (MI), ischemic stroke, hospitalization for heart failure (HHF), and initiation of renal replacement therapy (RRT) rates were captured from DECLARE TIMI 58 trial. One-way sensitivity analyses were conducted.Results: The budget impact model estimated 2,053,908 patients eligible for treatment with dapagliflozin from a societal perspective and 1,207,698 patients from the health insurance (HI) perspective. The new scenario allows for an initial savings of EGP121 million in the first year, which increased to EGP243 and EGP365 million in the second and third years, respectively. The total cumulative savings from a societal perspective were estimated at EGP731 million. Dapagliflozin allows for savings of EGP71, EGP143, and EGP215 million in the first, second and third years respectively, from the HI perspective, with total cumulative savings of EGP430 million over the 3 years.Conclusion: Treating T2DM patients using dapagliflozin instead of conventional medications, maximizes patients' benefits and decreases total costs due to drug cost offsets from fewer cardiovascular and renal events. The adoption of dapagliflozin is a budget-saving treatment option, resulting in substantial population-level health gains due to reduced event rate and cost savings from the perspective of the national healthcare system.

Reducing the Burden of Diabetes Treatment: A Review of Low-cost Oral Hypoglycemic Medications.

BACKGROUND: The vast majority of individuals diagnosed with diabetes are low/middle income and may have access to only three of the 11 oral hypoglycemic medications (OHMs) due to cost: metformin intermediate release (IR) or extended release (ER), sulfonylureas (glimepiride, glipizide, glyburide), and pioglitazone. Sulfonylureas and pioglitazone have had significant controversy related to potential adverse events, but it remains unclear whether these negative outcomes are class, drug, or dose-related. OBJECTIVE: We conducted a narrative review of low-cost OHMs. METHODS: We evaluated the maximum recommended (MAX) compared to the most effective (EFF) daily dose, time-to-peak change in HbA1c levels, and adverse events of low-cost oral hypoglycemic medications. RESULTS: We found that the MAX was often greater than the EFF: metformin IR/ER (MAX: 2,550/2,000 mg, EFF: 1,500-2,000/1,500-2,000 mg), glipizide IR/ER (MAX: 40/20 mg, EFF: 20/5 mg), glyburide (MAX: 20 mg, EFF: 2.5-5.0 mg), pioglitazone (MAX: 45 mg, EFF: 45 mg). Time-to-peak change in HbA1c levels occurred at weeks 12-20 (sulfonylureas), 25-39 (metformin), and 25 (pioglitazone). Glimepiride was not associated with weight gain, hypoglycemia, or negative cardiovascular events relative to other sulfonylureas. Cardiovascular event rates did not increase with lower glyburide doses (p<0.05). Glimepiride and pioglitazone have been successfully used in renal impairment. CONCLUSION: Metformin, glimepiride, and pioglitazone are safe and efficacious OHMs. Prescribing at the EFF rather than the MAX may avoid negative dose-related outcomes. OHMs should be evaluated as individual drugs, not generalized as a class, due to different dosing and adverse-event profiles; Glimepiride is the preferred sulfonylurea since it is not associated with the adverse events as others in its class.

The cost-effectiveness of metformin in pre-diabetics: a systematic literature review of health economic evaluations.

Objectives: Our aim was to systematically identify and appraise cost-effectiveness studies of metformin in prediabetic subjects.Methods: A systematic literature review was conducted and reported according to standard guidlines. The search was conducted in PubMed, Embase, International Society for Pharmacoeconomics and Outcomes Research (ISPOR) presentation database and the Cost-Effectiveness Analysis (CEA) and Center for Reviews and Dissemination (CRD) registries. All cost-effectiveness studies assessing metformin in prediabetic patients were included.Results: Twenty-three reports were included. Metformin and intensive lifestyle changes (ILC) interventions were always cost-effective compared to placebo. ILC was cost-effective and sometimes dominant compared to metformin. Metformin was cost-saving compared to ILC in the short and medium-term. Although, in the long term, metformin was more expensive than ILC in terms of direct medical costs, when indirect non-medical costs are included, metformin less expensive than ILC. One study reported that for patients with Body Mass Index (BMI) higher than 30 kg/m2, metformin is a cost-effective strategy compared to placebo and ILC. However, this finding was not confirmed by other retrieved studies.Conclusion: ILC is cost-effective compared to metformin and, both of them are cost-effective compared to placebo. Metformin may be cost-saving in the short- to medium-term and possibly in the long-term.

Evaluation of the Short-Term Cost-Effectiveness of IDegLira Versus Basal Insulin and Basal-Bolus Therapy in Patients with Type 2 Diabetes Based on Attainment of Clinically Relevant Treatment Targets.

BACKGROUND: Effective glycemic control can reduce the risk of complications and their related costs in patients with type 2 diabetes (T2D). Many patients fail to reach hemoglobin A1c (HbA1c) ≤ 6.5% or < 7.0%, often due to adverse effects of treatment, such as hypoglycemia and weight gain. Glycemic targets should be individualized and consider multiple factors, including the risk of adverse events and the patient's characteristics and comorbid conditions. OBJECTIVE: To compare the odds and annual cost of achieving treatment targets, which incorporate HbA1c targets of < 7.5%, < 8.0%, and ≤ 9.0%, with insulin degludec/liraglutide (IDegLira) versus basal insulin and basal-bolus therapy. METHODS: This is a post hoc analysis of the DUAL V and DUAL VII 26-week trials, which randomized patients with T2D uncontrolled (HbA1c 7%-10%) on insulin glargine 100 units/mL (IGlar U100) and metformin to IDegLira or continued IGlar U100 titration (DUAL V) or IGlar U100 + insulin aspart (DUAL VII), all with metformin. Proportions of patients achieving HbA1c targets (< 7.5%, < 8.0%, and ≤ 9.0%) by the end of trial were assessed via 3 outcomes: alone, without either hypoglycemia or weight gain (double composite outcome), or without a combination of hypoglycemia and weight gain (triple composite outcome). The cost per patient achieving the triple composite outcome at each HbA1c target (< 7.5%, < 8.0%, and ≤ 9.0%) was calculated by dividing the annual cost of treatment by the proportion of patients achieving the target. This short-term (1-year) cost-effectiveness analysis was conducted from the perspective of a U.S. health care payer. RESULTS: More patients achieved HbA1c < 7.5% (P < 0.0001) and < 8.0% (P = 0.0003), and a similar percentage achieved HbA1c ≤ 9.0% with IDegLira versus IGlar U100 (DUAL V). Similar proportions of patients achieved all 3 HbA1c targets with IDegLira compared with basal-bolus therapy (DUAL VII). The odds of achieving double or triple composite outcomes were significantly higher for IDegLira versus IGlar U100 or basal-bolus for all 3 HbA1c targets (P < 0.0001 in each case) in both trials. For each $1 spent on IDegLira, the equivalent annual costs per patient to achieve HbA1c targets of < 7.5%, < 8.0%, or ≤ 9.0% without hypoglycemia and without weight gain were $2.43, $2.10, and $2.05, respectively, for IGlar U100 and $6.33, $5.80, and $6.06, respectively, for basal-bolus therapy. CONCLUSIONS: Based on data from DUAL V and DUAL VII, this analysis showed that a greater or similar proportion of patients with T2D reached HbA1c targets with IDegLira compared with IGlar U100/basal-bolus therapy. Odds of achieving double or triple composite outcomes of HbA1c reduction without hypoglycemia and/or without weight gain were greatest for IDegLira. Short-term cost analyses based on the triple composite outcomes suggest that IDegLira is a cost-effective treatment option in the United States compared with either uptitration of IGlar U100 or basal-bolus therapy. DISCLOSURES: This study was supported by Novo Nordisk A/S. The analysis was based on the DUAL V (NCT01952145) and DUAL VII (NCT02420262) trials, which were funded and conducted by Novo Nordisk. This post hoc analysis was conceived and interpreted by the authors and drafted with medical writing support that was funded by Novo Nordisk. Novo Nordisk also reviewed the manuscript for medical accuracy. Hunt and Malkin are employees of Ossian Health Economics and Communications, which received consulting fees from Novo Nordisk during the conduct of this study and has received consulting fees from Novo Nordisk, unrelated to this study. Mocarski, Ranthe, and Schiffman are employees of Novo Nordisk and Novo Nordisk A/S. Cannon has received speaker fees/honoraria from Abbvie, Amgen, and Janssen; speaker fees from Novo Nordisk; and has stock ownership in Novo Nordisk. Bargiota has received speaker fees/honoraria from AstraZeneca, Eli Lilly, MSD, Novo Nordisk, Sanofi, Boehringer Ingelheim, and Novartis. Billings has received personal fees from Novo Nordisk, Sanofi, and Dexcom, unrelated to this study. Leiter reports grants and personal fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Merck, Novo Nordisk, Sanofi, Servier, and GSK, unrelated to this study. Doshi has no relevant conflicts of interest to disclose. Parts of this study were presented as a poster at the AMCP Managed Care & Specialty Pharmacy Annual Meeting; April 23-26, 2018; Boston, MA.

Cost Utility of Sodium-Glucose Cotransporter 2 Inhibitors in the Treatment of Metformin Monotherapy Failed Type 2 Diabetes Patients: A Systematic Review and Meta-Analysis.

OBJECTIVES: Type 2 diabetes mellitus (T2DM) and associated ailments are leading economic burdens to society. Sodium glucose cotransporter-2 (SGLT2) inhibitors are recent antidiabetic medications with beneficial clinical efficacy. This meta-analysis was conducted to quantitatively pool the incremental net benefit of SGLT2 inhibitors in T2DM patients who failed metformin monotherapy. METHODS: Relevant economic evaluation studies of T2DM patients were identified from PubMed, Scopus, ProQuest, the Cochrane Library, and the Tufts Cost-Effective Analysis Registry until June 2018. Studies were eligible if they studied T2DM patients who failed metformin monotherapy and assessed the cost-effectiveness/utility between SGLT2 inhibitors and other treatments. Details of the study characteristics, economic model inputs, costs, and outcomes were extracted. Risk of bias was assessed using the biases in economic studies (ECOBIAS) checklist. The incremental net benefit was calculated with monetary units adjusting for purchasing power parity for 2017 US dollars. This was then pooled across studies stratified by the country's level of income using a random-effect model if heterogeneity was present and with a fixed-effect model otherwise. Heterogeneity was assessed using the Q test and I2 statistic. RESULTS: A total of 13 studies with 22 comparisons, mainly from high-income countries, were eligible. Six and 4 studies compared SGLT2 with dipeptidyl peptidase-4 inhibitors (DPP4i) and sulfonylureas, respectively. The pooled incremental net benefits (95% confidence interval) for these corresponding comparisons were $164.95 (-$534.71 to $864.61; I2 = 0%) and $3675.09 ($1656.46-$5693.71; I2 = 85.4%), respectively. These results indicate that SGLT2s were cost-effective in comparison with sulfonylureas but not DPP4i. CONCLUSION: SGLT2s were cost-effective as compared with sulfonylureas but not DPP4i. Most of the evidence was from high-income countries with few comparative drug groups, and the results might not be representative of the actual global scenario. Further studies from middle and lower economies and other comparators are still required.

Cost-effectiveness analysis of metformin with enzalutamide in the metastatic castrate-resistant prostate cancer setting.

INTRODUCTION: Enzalutamide (Enza) is an effective treatment for metastatic castrate-resistant prostate cancer (mCPRC). However, Enza is not cost-effective (CE) at willingness to pay (WTP) thresholds from $0-$125 000/quality adjusted life years (QALYs) and is therefore a strain on valuable health care dollars. Metformin (Met) is inexpensive (~$8.00/month) and is thought to improve prostate cancer specific and overall survival compared to those not taking Met. We hypothesized that there must be an added effect Met could provide that would make Enza CE thereby alleviating this financial strain on government health care budgets. MATERIALS AND METHODS: We constructed a Markov model and performed a threshold analysis to narrow in on the added effect needed to make such a combination therapy cost-effective at various WTP thresholds. RESULTS: At a WTP threshold of $50 000/QALY Enza + Met is unlikely to be CE unless it increases Enza's efficacy by more than 30%. At a WTP threshold of $100 000, Enza + Met could be CE barring Met adds 18.73% to the efficacy of Enza. CONCLUSIONS: Enza + Met is unlikely to be CE at WTP thresholds less than $100 000/QALY; these results make sense because a therapy that is not CE at these WTP thresholds by itself is unlikely to be CE with an adjuvant therapy that keep a patient on such a treatment for even longer. Finally, our model suggests that the mCRPC setting is not the optimal place to trial adding Met as the relative costs are high and utility values low.

Drug price, dosage and safety: Real-world evidence of oral hypoglycemic agents.

OBJECTIVES: Drug price reduction is one of the major policies to restrain pharmaceutical expenses worldwide. This study explores whether there is a relationship between drug price and clinical quality using real-world data. METHODS: Patients with newly-diagnosed type 2 diabetes receiving metformin or sulfonylureas during 2001 and 2010 were identified using the claim database of the Taiwan universal health insurance system. Propensity score matching was performed to obtain comparable subjects for analysis. Pharmaceutical products were categorized as brand-name agents (BD), highpriced generics (HP) or low-priced generics (LP). Indicators of clinical quality were defined as the dosage of cumulative oral hypoglycemic agents (OHA), exposure to other pharmacological classes of OHA, hospitalization or urgent visit for hypoglycemia or hyperglycemia, insulin utilization and diagnosis of diabetic complications within 1 year after diagnosis. RESULTS: A total of 40,152 study subjects were identified. A generalized linear mix model showed that HP and BD users received similar OHA dosages with comparable clinical outcomes. By contrast, LP users had similar outcomes to BD users but received a 39% greater OHA dosage. A marginally higher risk of poor glycemic control in LP users was also observed. CONCLUSIONS: Drug price is related to indicators of clinical quality. Clinicians and health authorities should monitor the utilization, effectiveness and clinical safety indicators of generic drugs, especially those with remarkably low prices.

Investigating the exposure of Iranian households to catastrophic health expenditure due to the need to purchase medicines.

BACKGROUND: Catastrophic health expenditure (CHE) is an indicator used by the World Health Organization (WHO) to assess equity in households' payments to the health system. In this paper, we prospectively calculated the population at risk of facing catastrophic expenditure due to purchasing three selected medicines (metformin, atorvastatin and amoxicillin) in Iran. METHOD: This study draws on the data set of the Iranian National Household Survey of 38244 households in Iran. CHE was calculated based on "capacity to pay" using different thresholds. RESULTS: 20, 16 and 3 households had to spend more than 40% of their capacity to pay on amoxicillin, atorvastatin and metformin respectively. Lowest priced generic (LPG) medicines were found more affordable than the original brand (OB) medicines. Age, literacy and gender of head of household, economic status, settlement, size and number of breadwinners in the households share important association with CHE. CONCLUSION: Requirement of these specific medicines for long-term may subject the Iranian households to CHE. The study demonstrates important and specific insights for health policy makers in Iran to protect the households from healthcare catastrophes.

Cost-effectiveness of first-line versus delayed use of combination dapagliflozin and metformin in patients with type 2 diabetes.

The present study sought to evaluate the cost-effectiveness of first-line (immediate) versus delayed use of combination dapagliflozin and metformin in patients with type 2 diabetes, from the perspective of the Australian healthcare system. We developed a Markov model to simulate the progress of subjects with type 2 diabetes. Decision analysis was applied to assess the cost-effectiveness of first-line combination dapagliflozin and metformin versus first-line metformin monotherapy followed by gradual addition of dapagliflozin over time. Transition probabilities, costs (in Australian dollars) and utility data were derived from published sources. All costs, years of life lived and quality adjusted life years (QALYs) lived were discounted at an annual rate of 5%. Over a 20-year model period, first-line use of combination dapagliflozin and metformin was predicted to reduce the onset of hospitalisation of heart failure, cardiovascular deaths and all cause deaths by 5.5%, 57.6% and 29.6%, respectively. An additional 2.5 years of life (discounted) and 1.9 QALYs (discounted) would be gained per patient, at a cost of AUD $23,367 (discounted) per person. These figures equated to AUD $9,535 per years of life saved (YoLS) and AUD $12,477 per QALYs saved. Sensitivity analyses indicated the results to be robust. Compared to first-line metformin monotherapy followed by gradual addition of dapagliflozin, first-line use of combination dapagliflozin and metformin is likely to be a cost-effective approach to the management of Australians with type 2 diabetes mellitus.

Cost-effectiveness analysis of dapagliflozin treatment versus metformin treatment in Chinese population with type 2 diabetes.

BACKGROUND AND OBJECTIVE: Dapagliflozin is the first SGLT2 inhibitor available in China, where the disease burden of diabetes and its complications is very heavy. Because a new diabetes treatment strategy for diabetes should consider its cost-effectiveness, compared with an existing treatment, this study aimed to examine the cost-effectiveness between dapagliflozin and metformin treatment in China. METHODS: The Cardiff Diabetes Model (CDM) was used to estimate cost effectiveness and macro- and micro-vascular outcomes of dapagliflozin vs metformin. The CDM effectiveness inputs were derived from indirect comparative efficacy data from meta-analysis of 71 studies comparing monotherapy and add-on therapy of dapagliflozin vs metformin: dapagliflozin or metformin monotherapy, add-on therapy with other oral hypoglycemic agents, and add-on therapy with insulin. Direct medication costs and medical costs on treating diabetes were calculated based on published and local sources. A discount rate of 3% was applied to both costs and health effects. Univariate and probabilistic sensitivity analyses (PSA) were performed to assess uncertainties. RESULTS: The total healthcare costs accumulated over the lifetime on dapagliflozin treatment arm was 8,626 Chinese yuan higher than the metformin treatment arm for an individual patient, and the quality adjusted life years (QALYs) gained with dapagliflozin treatment was 0.8 more than metformin treatment. Therefore, an incremental cost-effectiveness ratio was 10,729 yuan per QALY gained for dapagliflozin treatment arm vs metformin treatment arm. The cost-effectiveness results were robust to various sensitivity analyses. CONCLUSION: Dapagliflozin treatment was more cost-effective compared with metformin treatment for Chinese type 2 diabetes patients. However, the findings of favorable cost-effectiveness results for dapagliflozin are largely driven by the effects of favorable weight profile on clinical, utility, and costs in the Cardiff model.

Comparison of healthcare resource utilization and costs in patients with type 2 diabetes initiating dapagliflozin versus sitagliptin.

AIMS: To compare healthcare costs and utilization in patients with type 2 diabetes (T2D) who initiated dapagliflozin (DAPA) with costs and utilization in those who initiated sitagliptin (SITA) in a real-world setting. MATERIALS AND METHODS: This was a retrospective study of health plan enrollees in two US commercial claims databases or Medicare Part D. The study population comprised adult patients with T2D who initiated DAPA or SITA between January 1, 2014 and April 30, 2015. DAPA and SITA initiators were propensity-score-matched, and healthcare utilization and costs during the 1-year follow-up period were compared. Analyses were conducted separately for patients with evidence of oral antidiabetic drug (OAD) monotherapy use at baseline. RESULTS: A total of 2722 patients were included in each matched cohort. Follow-up unadjusted all-cause costs ($16 065 and $17 281; P = 0.135) and diabetes-related costs ($9697 and $9354; P = 0.539) were similar in the DAPA and SITA cohorts. Higher office and outpatient visit costs in the SITA group were offset by higher pharmacy costs in the DAPA group. In the subgroup of 1804 patients with OAD monotherapy use at baseline, patients in the SITA group had higher total all-cause costs compared with those in the DAPA group ($14 884 vs. $12 353; P = 0.026). CONCLUSION: Patients who initiated DAPA or SITA had similar all-cause and diabetes-related healthcare costs over 1 year of follow-up. In the subgroup of patients treated with OAD monotherapy at baseline (84% metformin monotherapy), those who initiated DAPA as add-on therapy had lower costs than patients who added SITA.

Availability and affordability of essential medicines for diabetes across high-income, middle-income, and low-income countries: a prospective epidemiological study.

BACKGROUND: Data are scarce on the availability and affordability of essential medicines for diabetes. Our aim was to examine the availability and affordability of metformin, sulfonylureas, and insulin across multiple regions of the world and explore the effect of these on medicine use. METHODS: In the Prospective Urban Rural Epidemiology (PURE) study, participants aged 35-70 years (n=156 625) were recruited from 110 803 households, in 604 communities and 22 countries; availability (presence of any dose of medication in the pharmacy on the day of audit) and medicine cost data were collected from pharmacies with the Environmental Profile of a Community's Health audit tool. Our primary analysis was to describe the availability and affordability of metformin and insulin and also commonly used and prescribed combinations of two medicines for diabetes management (two oral drugs, metformin plus a sulphonylurea [either glibenclamide (also known as glyburide) or gliclazide] and one oral drug plus insulin [metformin plus insulin]). Medicines were defined as affordable if the cost of medicines was less than 20% of capacity-to-pay (the household income minus food expenditure). Our analyses included data collected in pharmacies and data from representative samples of households. Data on availability were ascertained during the pharmacy audit, as were data on cost of medications. These cost data were used to estimate the cost of a month's supply of essential medicines for diabetes. We estimated affordability of medicines using income data from household surveys. FINDINGS: Metformin was available in 113 (100%) of 113 pharmacies from high-income countries, 112 (88·2%) of 127 pharmacies in upper-middle-income countries, 179 (86·1%) of 208 pharmacies in lower-middle-income countries, 44 (64·7%) of 68 pharmacies in low-income countries (excluding India), and 88 (100%) of 88 pharmacies in India. Insulin was available in 106 (93·8%) pharmacies in high-income countries, 51 (40·2%) pharmacies in upper-middle-income countries, 61 (29·3%) pharmacies in lower-middle-income countries, seven (10·3%) pharmacies in lower-income countries, and 67 (76·1%) of 88 pharmacies in India. We estimated 0·7% of households in high-income countries and 26·9% of households in low-income countries could not afford metformin and 2·8% of households in high-income countries and 63·0% of households in low-income countries could not afford insulin. Among the 13 569 (8·6% of PURE participants) that reported a diagnosis of diabetes, 1222 (74·0%) participants reported diabetes medicine use in high-income countries compared with 143 (29·6%) participants in low-income countries. In multilevel models, availability and affordability were significantly associated with use of diabetes medicines. INTERPRETATION: Availability and affordability of essential diabetes medicines are poor in low-income and middle-income countries. Awareness of these global differences might importantly drive change in access for patients with diabetes. FUNDING: Full funding sources listed at the end of the paper (see Acknowledgments).