A short-term economic evaluation of early insulin therapy compared to oral anti-diabetic drugs in order to reduce the major adverse events in type 2 diabetes patients in Iran.

OBJECTIVE: While there are some recommendations about early insulin therapy in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, there is not sufficient evidence on this strategy's cost-effectiveness. This study compared early insulin therapy versus oral anti-diabetic drugs (OADs) for managing T2DMusing a cost-effectiveness analysis approach in Iran. METHODS: In this economic evaluation, a decision analytic model was designed. The target population was newly diagnosed type 2 diabetic patients, and the study was carried out from the perspective of Iran's healthcare system with a one-year time horizon. Basal insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, and Thiazolidinediones (TZDs) were compared in this evaluation. The main outcome for assessing the effectiveness of each intervention was the reduction in the occurrence of diabetes complications. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and deterministic and probabilistic sensitivity analyses were carried out. RESULTS: The DPP-4 inhibitors strategy was the dominant strategy with the highest effectiveness and the lowest cost. Early insulin therapy was dominated (ICER: $-53,703.18), meaning that it was not cost-effective. The sensitivity analyses consistently affirmed the robustness of the base case findings. The probabilistic sensitivity analysis indicated probabilities of 77%, 22%, and 1% for DPP-4 inhibitors, TZDs strategies, and early insulin therapy, respectively, in terms of being cost-effective. CONCLUSION: In terms of cost-effectiveness, early insulin therapy was not cost-effective compared to OADs for managing newly diagnosed T2DM patients. Future studies in this regard, utilizing more comprehensive evidence, can yield more accurate results.

Burden of Illness of Type 2 Diabetes Mellitus in the Kingdom of Saudi Arabia: A Five-Year Longitudinal Study.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is associated with huge clinical and economic burden in the Kingdom of Saudi Arabia (KSA) which can be curtailed by efficacious treatment. In order to achieve this, current treatment pathways for T2DM and associated costs need to be assessed. METHODS: A longitudinal cohort review was conducted to collect country-specific and patient-specific clinical data, over a minimum observation period of 5 years in the KSA. Patient demographics, clinical characteristics and treatment patterns were recorded. The IQVIA Core Diabetes Model (CDM) version 9.5 Plus was used to assess the burden of illness, which included long-term projections of clinical (life expectancy [LE], quality-adjusted life-years [QALYs], event rates of diabetes-related complications) and direct medical cost (per-patient annual or lifelong [50 years]) outcomes of the most commonly used first-line (1st-line) regimens for T2DM from a payer perspective in the KSA. RESULTS: Data were collected from a subpopulation of 638 patients from 15 participating centres. There was an equal gender representation with a majority of the patients belonging to Arabian/Saudi ethnicity (71.0%). Biguanides (81.5%), sulfonylureas (51.6%), dipeptidyl peptidase 4 (DPP4) inhibitors (26.2%) and fast-acting insulins (17.2%) were the most prescribed 1st-line agents. The most frequently used 1st-line regimens resulted in an estimated LE of 25-28 years, QALYs of 18-21 years and lifelong total cost of illness of 201,377-437,371 Saudi Arabian riyal (53,700-116,632 US dollars). CONCLUSION: Our study addresses gaps in the current research by providing a complete landscape of baseline demographic, clinical characteristics and treatment patterns from a heterogeneous group of patients with T2DM in the KSA. Additionally, the burden of illness analysis using CDM showed substantially higher cost of T2DM care from a payer perspective in the KSA.

Healthcare resource utilization and healthcare costs in patients with type 2 diabetes mellitus initiating sodium-glucose cotransporter 2 inhibitors vs dipeptidyl peptidase-4 inhibitors in Japan: A real-world administrative database analysis.

AIMS/INTRODUCTION: Healthcare resource utilization (HCRU) and healthcare costs are important factors to consider when selecting appropriate treatment for type 2 diabetes mellitus. We compared the HCRU and healthcare costs of sodium-glucose cotransporter 2 inhibitors (SGLT2i) vs dipeptidyl peptidase-4 inhibitors (DPP4i) in patients with type 2 diabetes mellitus in Japan. MATERIALS AND METHODS: This was a Japanese retrospective cohort study conducted using the JMDC Claims Database (January 1, 2015-December 31, 2021). Patients newly treated with an SGLT2i (31,872 patients) or a DPP4i (73,279 patients) were matched 1:1, using propensity score, after excluding patients without continuous SGLT2i or DPP4i prescriptions after the index date. HCRU and healthcare costs were compared between the treatment groups in the full cohort and subcohorts/subgroups of different baseline characteristics, including body mass index (BMI). RESULTS: After matching, patient characteristics were well balanced (17,767 patients each). Patients receiving an SGLT2i vs those receiving a DPP4i had significantly lower numbers of hospitalizations per person per month (PPPM) and outpatient visits PPPM, and had shorter lengths of stay per hospitalization. Healthcare costs, including all-cause overall healthcare costs PPPM and all-cause hospitalization costs PPPM, were generally lower in patients receiving an SGLT2i than those receiving a DPP4i. Similar results were observed among patients with a higher BMI but not among patients with a lower BMI. CONCLUSIONS: SGLT2i were associated with lower HCRU and healthcare costs than DPP4i, suggesting economic benefits with SGLT2i vs DPP4i in type 2 diabetes mellitus management.

Dipeptidyl peptidase-4 inhibitors alleviate cognitive dysfunction in type 2 diabetes mellitus.

BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) are commonly at high risk for developing cognitive dysfunction. Antidiabetic agents might be repurposed for targeting cognitive dysfunction in addition to modulation on glucose homeostasis. This study aimed to evaluate the impact of dipeptidyl peptidase-4 inhibitors (DPP-4i) on cognitive function in T2DM. METHODS: PubMed, Embase, Cochrane Library and Web of Science were systematically searched from inception to September 30, 2023. Weighted mean differences were calculated using the Mantel-Haenszel (M-H) fixed or random effects model based on the degree of heterogeneity among studies. Heterogeneity was evaluated using a Chi-squared test and quantified with Higgins I2. Sensitivity analysis was performed with the leave-one-out method, and publication bias was evaluated according to Begg's and Egger's tests. RESULTS: Six clinical trials involving 5,178 participants were included in the pooled analysis. Administration of DPP-4i generally correlated with an increase of Mini-Mental State Examination (MMSE) scores (1.09, 95% CI: 0.22 to 1.96). DPP-4i alleviated cognitive impairment in the copying skill subdomain of MMSE (0.26, 95% CI: 0.12 to 0.40). Treatment with DPP-4i also resulted in an increase of Instrumental Activities of Daily Living (IADL) scores (0.82, 95% CI: 0.30 to 1.34). However, DPP-4i produced no significant effects on Barthel Activities of Daily Living (BADL) scores (0.37, 95% CI: -1.26 to 1.99) or other test scores. CONCLUSIONS: DPP-4i treatment favourably improved cognitive function in patients with T2DM. Further trials with larger samples should be performed to confirm these estimates and investigate the association of different DPP-4i with cognitive function among diabetic patients. TRIAL REGISTRATION IN PROSPERO: CRD42023430873.

Cost-Effectiveness of Newer Antidiabetic Drugs as Second-Line Treatment for Type 2 Diabetes: A Systematic Review.

INTRODUCTION: Evidence from cardiovascular outcome trials (CVOTs) for newer antidiabetic drugs is increasingly influencing revised recommendations for second-line therapy in type 2 diabetes (T2D). This systematic review aimed to compare the cost-effectiveness of newer antidiabetic drugs specified as sodium-glucose cotransporter 2 inhibitor (SGLT2i), glucagon-like peptide 1 receptor agonist (GLP-1RA), and dipeptidyl peptidase 4 inhibitor (DPP-4i) for T2D in a second-line setting. METHODS: A systematic review was conducted following the Preferred Reporting Items for Systematic Reviews (PRISMA) guidelines, and all relevant published studies were searched comprehensively in electronic databases, including PubMed, Embase, Web of Science, and International Health Technology Assessment database published from April 2023. The quality of the included studies was evaluated using Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 reporting checklists. RESULTS: We included 28 studies that met the inclusion criteria. Overall reporting of the identified studies largely met CHEERS 2022 recommendations. The CORE and Cardiff models were the most frequently utilized for pharmacoeconomic evaluation in T2D. Four studies consistently discovered that SGLT2i was more cost-effective than GLP-1RA in T2D who were not adequately controlled by metformin monotherapy. Four studies compared GLP-1RA with DPP-4i, sufonylurea (SU), or insulin. Except for one that demonstrated SU was cost-effective, all were GLP-1RA. Five studies revealed that SGLT2i was more cost-effective than DPP-4i or SU. Eleven studies indicated that DPP-4i was more cost-effective than traditional antidiabetic drugs. Four additional studies explored the cost-effectiveness of various antidiabetic drugs as second-line options, indicating that SU, SGLT2i, or meglitinides were more economically advantageous. The most common driven factors were the cost of new antidiabetic drugs. CONCLUSION: Newer antidiabetic drugs as second line are the cost-effective option for T2D from the cost-effectiveness perspective, especially SGLT2i.

Finding the most cost-effective option from commonly used Dipeptidyl peptidase-4 inhibitors in India: a systematic study.

OBJECTIVE: To identify a preferred and cost-effective drug among Dipeptidyl peptidase-4 inhibitors (DPP4Is) for Indian patients with T2DM. METHODS: We performed a systematic literature search using standard databases for relevant literature. Original studies comparing the efficacy and/or safety of different DPP4Is were included. Two authors independently performed the literature search, screening, and collected relevant data from the selected studies. The costs of all brands of individual DPP4Is were noted and compared for lowest, highest, and average cost. Finally, we summarized the information with respect to Efficacy, safety, suitability, and cost to find the most cost-effective DPP4I. RESULTS: We found 13 eligible studies containing data on 15,720 subjects. These studies showed similar efficacy (or better) and safety with teneligliptin as compared to other DPP4Is. Teneligliptin also showed additional benefits other than the glycemic control. The average cost per tablet of teneligliptin 20 mg was markedly lower as compared to sitagliptin, vildagliptin, and other commonly used DPP4Is. Teneligliptin also outscored other commonly used DPP4Is in India in suitability and seems to have better patient compliance. CONCLUSIONS: Teneligliptin 20 mg could be considered as the preferred and most cost-effective agent among commonly used DPP4Is for the effective management of patients with T2DM in India.

Association of Sodium-Glucose Cotransporter-2 Inhibitors With Incident Atrial Fibrillation in Older Adults With Type 2 Diabetes.

Importance: Sodium-glucose cotransporter-2 inhibitors (SGLT-2is) have demonstrated many cardiovascular and kidney function benefits for patients with type 2 diabetes (T2D). However, the results of SGLT-2i use in primary prevention of atrial fibrillation (AF) were inconsistent in clinical trials, and incident AF was not a prespecified end point. Objective: To examine incident AF with initiation of an SGLT-2i compared with initiation of a dipeptidyl peptidase-4 inhibitor (DPP-4i) or a glucagonlike peptide-1 receptor agonist (GLP-1RA) among older adults (aged ≥66 years) with T2D in routine clinical practice. Design, Setting, and Participants: A population-based new-user cohort study included older adults with T2D who had no history of AF and were enrolled in Medicare fee-for-service from April 1, 2013, to December 31, 2018. Data analysis was performed from June 28 to December 1, 2021. Exposures: To control for potential confounding, new users of SGLT-2i were 1:1 propensity score (PS)-matched to new users of DPP-4is or GLP-1RAs in 2 pairwise comparisons based on 138 baseline covariates. Main Outcomes and Measures: The primary outcome was incident AF, defined as an inpatient diagnosis code for AF. Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years, with their 95% CIs, were estimated in the PS-matched groups. Results: New users of SGLT-2is were 1:1 PS-matched to new users of a DPP-4i (n = 74 868) or GLP-1RA (n = 80 475). Overall, the mean (SD) age of study participants was 72 (5) years, and 165 984 were women (53.4%). The risk of incident AF was lower in the SGLT-2i group than the matched DPP-4i group (HR, 0.82; 95% CI, 0.76 to 0.89; RD, -3.7; 95% CI, -5.2 to -2.2 per 1000 person-years) or the matched GLP-1RA group (HR, 0.90; 95% CI, 0.83 to 0.98; RD, -1.8; 95% CI, -3.2 to -0.3 per 1000 person-years). Results were consistent across several sensitivity and subgroup analyses. Conclusions and Relevance: The findings of this study suggest that the initiation of an SGLT-2i was associated with a reduced risk of incident AF compared with a DPP-4i or GLP-1RA. The results may be helpful when weighing the potential risks and benefits of various glucose level-lowering agents in older adults with T2D.

Trends in add-on medications following metformin monotherapy for type 2 diabetes.

BACKGROUND: Although metformin is generally universally recommended as a first-line pharmacologic therapy for most people living with type 2 diabetes, second-line and third-line choices can require a tailored approach to achieve optimal blood glucose and glycated hemoglobin levels. OBJECTIVE: To examine national trends in second- and third-line antihyperglycemic medications following metformin monotherapy, comparing 2015 and 2019. METHODS: This retrospective cohort analysis of deidentified pharmacy claims from a large national pharmacy benefits manager from January 1, 2015, to December 31, 2015, and again in January 1, 2019, to December 31, 2019, included adults (aged ≥ 18 years) continuously enrolled in commercial or Medicare insurance plans who filled an index metformin prescription in either year. Proportions of patients by second-line and third-line antihyperglycemic class were calculated. RESULTS: Second-line use of sulfonylureas (-10.1%; P < 0.001), combination drugs (-3.0%; P < 0.001), and dipeptidyl peptidase-4 inhibitors (-2.0%; P = 0.031) significantly declined, whereas second-line use of sodium-glucose cotransporter 2 inhibitors (SGLT2is) (+4.9%; P < 0.001) and glucagon-like peptide-1 receptor agonists (GLP-1Ras) (+10.0%; P < 0.001) significantly increased. Similarly, third-line use of sulfonylureas declined (-5.5%; P = 0.005), whereas third-line use of SGLT2is (+3.4%; P = 0.005) and GLP-1RAs (+8.3%; P < 0.001) increased. Similar trends between 2015 and 2019 were found in commercial and Medicare subgroups. Among all groups in 2015 compared with 2019, sulfonylureas were the most prescribed second-line class and insulins the most common third-line class. Although SGLT2i and GLP-1RA together represented more than one-third of second-line and third-line prescriptions for commercially insured patients in 2019 (34.3% and 35.0%, respectively), these classes were less frequently prescribed in the Medicare subgroup (18% and 25.6%, respectively). CONCLUSIONS: This report provides updated second-line and third-line antihyperglycemic medication prescribing trends in the United States, which suggests that evidence-based guidelines are being used in practice to prevent complications and individualize diabetes care. DISCLOSURES: Ms Swart and Drs Peasah and Good are employed by UPMC Health Plan. Dr Neilson was employed by UPMC Health Plan at the time of the study. Drs Munshi and Henderson were employed by Evernorth at the time of the study.

Cost-effectiveness of sodium-glucose cotransporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors among patients with type 2 diabetes with and without established cardiovascular diseases: A model-based simulation analysis using 10-year real-world data and targeted literature review.

AIM: We conducted a model-based economic analysis of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus dipeptidyl peptidase-4 inhibitors (DPP4is) in patients with type 2 diabetes (T2D), with and without established cardiovascular diseases (CVDs), using 10-year real-world data. MATERIALS AND METHODS: A Markov model was utilized to estimate healthcare costs and quality-adjusted life-years (QALYs) over a 10-year simulation time horizon from a healthcare sector perspective, with both costs and QALYs discounted at 3% annually. Model inputs were derived from analyses of Taiwan's National Health Insurance Research Database or published studies of Taiwanese populations. The primary outcome measure was the incremental cost-effectiveness ratios (ICERs). Incorporated with our study findings, a targeted literature review was conducted to synthesize updated evidence on the cost-effectiveness of SGLT2is versus DPP4is. RESULTS: Over 10 years, use of SGLT2is versus DPP4is yielded ICERs of $3244 and $4186 per QALY gained for patients with T2D, with and without established CVDs, respectively. Results were robust across a series of sensitivity and scenario analyses, showing ICERs between $-1074 (cost-saving) and $8467 per QALY gained for patients with T2D with established CVDs and between $369 and $37 122 per QALY gained for patients with T2D without established CVDs. CONCLUSIONS: Use of SGLT2is versus DPP4is was highly cost-effective for patients with T2D regardless of their CVD history in real-world clinical practice. Our results extend current evidence by showing SGLT2is as an economically rational alternative over DPP4is for T2D treatment in routine care. Future research is warranted to explore the heterogeneous economic benefits of SGLT2is given diverse patient characteristics in clinical settings.

Dispensation Patterns of Glucose-Lowering Drugs in Newly Diagnosed Type 2 Diabetes: Routine Data Analysis of Insurance Claims in Germany.

AIMS: To describe dispensation patterns of glucose-lowering drugs in newly diagnosed type 2 diabetes in Germany. MATERIALS AND METHODS: Based on claims data from four statutory health insurances (German Pharmacoepidemiological Research Database,>25 million insurants), all individuals with newly diagnosed type 2 diabetes were identified. Eligible patients had a first diagnosis for type 2 diabetes between January 2012 and December 2016. We analyzed the dispensation patterns of first-line glucose-lowering therapies initiated in the year after diabetes diagnosis and patterns of second-line therapies dispensed one year after first-line treatment. RESULTS: A total of 356,647 individuals with newly diagnosed type 2 diabetes were included (average age [SD]: 63.5 [13.4] years; 49.3% males). Of the 31.6% of individuals who were pharmacologically treated in the year after diagnosis, metformin monotherapy was most frequently dispensed (73.1%), followed by dual therapy of metformin and dipeptidyl peptidase-4 inhibitors (DPP-4is) (6.4%), and monotherapy with DPP-4is (2.9%). From 2012 through 2016, sulfonylurea dispensations were reduced by more than 50%. Dispensations for combination therapies with DPP-4is increased up to 10.6%. Glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors contributed to 2% of all treatments. After a median of 5 months, 20.0% of individuals on pharmacological therapy initiated second-line glucose-lowering treatment. CONCLUSIONS: Data from German statutory health insurances (2012 to 2016) showed that most individuals with newly diagnosed type 2 diabetes were dispensed metformin monotherapy in line with diabetes care guidelines. A substantial decrease in the use of sulfonylureas was observed after the introduction of DPP-4i and GLP-1 receptor agonists.

Unmasking Fracture Risk in Type 2 Diabetes: The Association of Longitudinal Glycemic Hemoglobin Level and Medications.

CONTEXT: Fracture risk is underestimated in people with type 2 diabetes (T2D). OBJECTIVE: To investigate the longitudinal relationship of glycated hemoglobin (HbA1c) and common medications on fracture risk in people with T2D. METHODS: This retrospective population-based cohort study was conducted using de-identified claims and electronic health record data obtained from the OptumLabs Data Warehouse for the period January 1, 2007, to September 30, 2015. For each individual, the study was conducted within a 2-year HbA1c observation period and a 2-year fracture follow-up period. A cohort of 157 439 individuals with T2D [age ≥ 55 years with mean HbA1c value ≥ 6%] were selected from 4 018 250 US Medicare Advantage/Commercial enrollees with a T2D diagnosis. All fractures and fragility fractures were measured. RESULTS: With covariates adjusted, poor glycemic control in T2D individuals was associated with an 29% increase of all fracture risk, compared with T2D individuals who had adequate glycemic control (HR: 1.29; 95% CI, 1.22-1.36). Treatment with metformin (HR: 0.88; 95% CI, 0.85-0.92) and DPP4 inhibitors (HR: 0.93; 95% CI, 0.88-0.98) was associated with a reduced all fracture risk, while insulin (HR: 1.26; 95% CI, 1.21-1.32), thiazolidinediones (HR: 1.23; 95% CI, 1.18-1.29), and meglitinides (HR: 1.12; 95% CI, 1.00-1.26) were associated with an increased all fracture risk (All P value < 0.05). Bisphosphonates were associated similarly with increased fracture risk in the T2D and nondiabetic groups. CONCLUSION: Longitudinal 2-year HbA1c is independently associated with elevated all fracture risk in T2D individuals during a 2-year follow-up period. Metformin and DPP4 inhibitors can be used for management of T2D fracture risk.

The diminishing cost-effectiveness of the newer glucose-lowering drug classes in the United States: 2010-2018.

BACKGROUND: The difference between the costs of the newer and older glucose-lowering drugs (GLMs) has been steadily increasing since 2010. In 2018, newer drugs cost 8-12 times more than older drugs (except for insulin). This study aimed to understand how the cost change influenced the cost-effectiveness of the newer GLMs. METHODS: Based on our previous literature review on US-based cost-effectiveness studies comparing newer (i.e. dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide 1 receptor agonists (GLP1-RA), and sodium-glucose transport protein 2 inhibitors) with older GLMs, we identified 12 studies that reported the cost-effectiveness of newer drugs based on drug costs estimated before 2010. We updated the corresponding cost-effectiveness of each study by replacing the old cost estimates with 2018 estimates from the 2018 IBM MarketScan Commercial Claims Databases. The time window and willingness to pay threshold were consistent with the original studies. RESULTS: Only 8% of the original studies suggested that the older drugs were cost-effective. However, 58% of studies were in favor of the older drugs after the cost update. Among the four studies comparing newer drugs with thiazolidinediones, all the original results favored newer drugs. However, all studies suggested thiazolidinedione to be cost-effective in the updated analysis. For the four studies comparing newer drugs with sulfonylureas, two studies suggested the sulfonylureas to be cost-effective after the cost update. All four studies suggested newer drugs to be cost-effective when compared with insulin in the original study. Only 1 flipped its conclusion when 2018 costs were used. Our sensitivity analysis shows that our results are robust under a 30% rebate. CONCLUSION: Significant changes in the cost of GLMs have impacted the economic value of different GLM classes substantially. More cost-effectiveness analyses are warranted to support the drug choice in T2DM management.

Cost-effectiveness of intensification with SGLT2 inhibitors for type 2 diabetes.

OBJECTIVES: Using a US payer perspective, this study aimed to compare the lifetime cost-effectiveness of adding sodium-glucose cotransporter 2 (SGLT2) inhibitors vs switching to glucagon-like peptide 1 receptor agonists (GLP-1 RAs) among patients with type 2 diabetes who were not at glycated hemoglobin A1c target after dual therapy with metformin and dipeptidyl peptidase-4 (DPP-4) inhibitors. STUDY DESIGN: The cost-effectiveness analysis was performed with the validated IQVIA Core Diabetes Model. Treatment effects were obtained from randomized clinical trials with economic data based on published literature. METHODS: Risk of treatment-emergent adverse events and complications were simulated using submodels informed by published risk equations adjusted for patient characteristics, physiological parameters, and history of complications. Outcomes included cumulative incidence of micro- and macrovascular complications, life-years (LYs), quality-adjusted life-years (QALYs), and total costs. Scenario analyses were performed to assess robustness of results to variations in clinical and cost inputs and assumptions. RESULTS: Over a lifetime time horizon, adding an SGLT2 inhibitor dominated the strategy of switching to a GLP-1 RA, improving survival by 0.049 LYs and 0.026 QALYs, and was associated with cost savings of $9511. The majority of the scenario analyses confirmed dominance of the DPP-4 inhibitor + SGLT2 inhibitor pathway vs the GLP-1 RA pathway. The probabilistic sensitivity analysis reinforced the base-case finding of cost savings while gaining QALYs. CONCLUSIONS: Intensification with an SGLT2 inhibitor on top of a DPP-4 inhibitor demonstrated slightly better efficacy and cost savings compared with switching to a GLP-1 RA in patients not at glycemic goal with metformin and a DPP-4 inhibitor.

Comparative safety of dipeptidyl peptidase-4 inhibitors and sulfonylureas among frail older adults.

BACKGROUND: Studies comparing dipeptidyl peptidase-4 inhibitors (DPP4Is) to sulfonylureas (SUs) are unavailable for frail older adults, especially nursing home (NH) residents. We examined the effects of DPP4Is versus SUs on severe adverse glycemic events, cardiovascular events, and death among NH residents. METHODS: We conducted a national retrospective cohort study of long-stay NH residents aged ≥65 years using 2008-2010 national US Minimum Data Set clinical assessment data and linked Medicare claims. Exposure was new DPP4I versus new SU use assessed via Medicare Part D drug claims. One-year outcomes were severe hypoglycemia, severe hyperglycemia, acute myocardial infarction (AMI), heart failure (HF), major adverse cardiovascular events plus HF (MACE+HF), and death. We compared outcomes after propensity score matching using Cox proportional hazards regression models. RESULTS: The cohort (N = 2016) had a mean (SD) age of 81 (8.1) years and was 72% female. Compared with SU users, DPP4I users had a lower 1-year rate of severe hypoglycemic events (HR = 0.57, 95% CI 0.34-0.94), but statistically similar rates of severe hyperglycemic events (HR = 0.94, 95% CI 0.52-1.72), AMI (HR = 0.76, 95% CI 0.44-1.30), HF (HR = 1.01, 95% CI 0.79-1.30), MACE+HF (HR = 0.90, 95% CI 0.72-1.12), and death (HR = 0.97, 95% CI 0.86-1.10). CONCLUSIONS: DPP4Is should be a preferred treatment option over SUs for NH residents and other frail older adults given the importance of avoiding hypoglycemia.

Cost and clinical impact of a nonmedical DPP-4 inhibitor switch in patients with diabetes.

BACKGROUND: Nonmedical formulary switches (NMFS) routinely occur in managed health care plans and involve changing preferred medications for reasons outside of clinical considerations. The cost implications of NMFS are infrequently published and the clinical outcomes rarely assessed. OBJECTIVE: To assess the real-world clinical and cost implications of an NMFS involving sitagliptin and linagliptin. METHODS: An NMFS was made to the Geisinger Health Plan (GHP) commercial, health care reform, and Medicaid formularies on February 1, 2018, involving a change in preferred medication from sitagliptin to linagliptin. Claims data from GHP and clinical information from electronic health records of the Geisinger Health System were used to evaluate the cost and clinical impact of this change. Patients aged 18 years or older who were continuously enrolled in a GHP commercial, health care reform, or Medicaid plan throughout the entire study period and had at least 1 fill for sitagliptin during the preswitch phase were included in the study. We investigated the differences in various clinical and economic outcomes from pre- to postswitch among those who switched and remained adherent to the new preferred therapy throughout the 12-month postperiod ("linagliptin switch" group) and patients who did not ("other switch" group). Clinical outcomes included all-cause hospitalization, diabetes-related hospitalization, and glycosylated hemoglobin (HbA1c), while economic measures included changes in per member per month (PMPM) spending. The negative binomial regression model was used to estimate utilization counts. A generalized linear model with a log link and gamma distribution was used to analyze cost data. RESULTS: 1,203 patients met the inclusion criteria. Of these, 501 (41.6%) individuals switched to and remained at least 80% adherent to linagliptin in the postperiod, while 702 (58.4%) did not. No difference between groups was found when comparing the pre- to postswitch change in all-cause hospitalization (incidence rate ratio (IRR) = 1.46, 95% CI = 0.66-3.23, P = 0.3436) or diabetes-related hospitalization (IRR = 1.39, 95% CI = 0.62-3.10, P = 0.4203). Additionally, no difference was found between groups regarding the change in HbA1c 12-month postswitch compared with baseline (difference between groups = -0.10%, 95% CI = -0.39%-0.19%, P = 0.4962). Total PMPM spending was 43% higher in the other switch group compared with the linagliptin switch group (IRR = 1.43, 95% CI = 1.25-1.63, P < 0.0001). This trend was driven by 92% higher medical PMPM spending in the other switch group compared with the linagliptin switch group (IRR = 1.92, 95% CI = 1.58-2.33, P < 0.0001) but was offset by 12% lower pharmacy PMPM spending in the other switch group (IRR = 0.88, 95% CI = 0.82-0.95, P = 0.0009). CONCLUSIONS: An NMFS from sitagliptin to linagliptin resulted in overall health plan savings with no significant changes in health outcomes. DISCLOSURES: Funding for this study was provided by Geisinger Health System, which had no role in the study outside of a final review of the submitted manuscript. Johns and Gionfriddo are Geisinger employees. The authors report no financial conflicts of interest.

Inhibidores de dipeptidil-peptidasa 4 en pacientes con prediabetes o síndrome metabólico / Dipeptidyl-peptidase 4 inhibitors in patients with prediabetes or metabolic syndrome

CONTEXTO CLÍNICO: La Diabetes Mellitus (DM) es un desorden metabólico de etiología múltiple que se caracteriza por hiperglucemia crónica con alteraciones en la secreción y/o en la acción de la insulina. Dentro de esta entidad, la DM tipo 2 representa alrededor del 90% de las personas con DM.2 Se estima que en Argentina la prevalencia de DM tipo 2 es de un 6,2%, generando 15.545 muertes por diabetes/año en personas entre 20 y 79 años. Dentro de los factores de riesgo para el desarrollo de DM tipo 2 se encuentran el síndrome metabólico y la prediabetes.3,4 El síndrome metabólico es una entidad con diferentes definiciones (ANEXO IV), pero la mayoría de estas considera como síndrome metabólico a la presencia de dos/tres o más de los siguientes criterios: aumento de glucosa en plasma, obesidad (particularmente abdominal), hipertensión, aumento de triglicéridos y una disminución de lipoproteínas de alta densidad (HDL). La presencia de síndrome metabólico representa un aumento en el riesgo relativo para el desarrollo de DM tipo 2 de entre 3,5 y 5,1 veces. Por otra parte, la prediabetes es una fase previa al desarrollo de diabetes caracterizado por una prueba de tolerancia a la glucosa alterada y/o glucosa en ayunas alterada, y se estima que aproximadamente el 70% de las personas con prediabetes llegan a desarrollar DM tipo 2. Estas dos entidades están muy relacionadas, tanto es así que la prediabetes es uno de los criterios de síndrome metabólico, y a su vez, el aumento de triglicéridos, la disminución del HDL, y el sobrepeso son factores de riesgo para desarrollar prediabetes. TECNOLOGÍA: Los inhibidores de dipeptidil peptidasa 4 (DPP4), entre los que se encuentran: vildagliptina, saxagliptina, linagliptina, sitagliptina, tenegliptina, alogliptina, son una clase de hipoglucemiantes orales cuyo control glucémico se basa en la inhibición del DPP4, enzima que degrada incretinas como el péptido similar al glucagón 1 (GLP-1) y el polipéptido insulinotrópico dependiente de la glucosa (GIP), los cuales se liberan por el intestino durante el día y tras la ingesta. Esto lleva a un aumento de la vida media de estas enzimas y por consiguiente aumenta la liberación de insulina reduciendo los niveles de glucagón con un comportamiento dependiente del nivel de glucemia. OBJETIVO: El objetivo del presente informe es evaluar la evidencia disponible acerca de la eficacia, seguridad y aspectos relacionados a las políticas de cobertura del uso de inhibidores de DPP4 para pacientes con prediabetes o síndrome metabólico sin diabetes mellitus. MÉTODOS: Se realizó una búsqueda en las principales bases de datos bibliográficas, en buscadores genéricos de internet, y financiadores de salud. Se priorizó la inclusión de revisiones sistemáticas (RS), ensayos clínicos controlados aleatorizados (ECAs), evaluaciones de tecnologías sanitarias (ETS), evaluaciones económicas, guías de práctica clínica (GPC) y políticas de cobertura de diferentes sistemas de salud. RESULTADOS: Se incluyeron cinco ECAs, una RS, cinco GPC, ocho informes de políticas de cobertura de inhibidores de DPP4 en prediabetes o enfermedades metabólicas sin diabetes mellitus. CONCLUSIONES: Evidencia de muy baja calidad no permite concluir sobre la eficacia y seguridad de los inhibidores de dipeptidil-peptidasa 4 (DPP4) en pacientes con prediabetes o síndrome metabólico sin diabetes mellitus (DM). Existen resultados promisorios sobre desenlaces importantes, como la reducción de la incidencia de DM tipo 2 o la vuelta a la normoglucemia asociado al uso de inhibidores de DPP4 combinado con metformina, en comparación a metformina sola en pacientes prediabéticos. Sin embargo, actualmente las limitaciones metodológicas de la evidencia encontrada no permiten formular una recomendación con relación al uso de los inhibidores de dipeptidil-peptidasa 4 en esta indicación. La guía de Práctica Clínica Nacional sobre Prevención, Diagnóstico y Tratamiento de la Diabetes Mellitus Tipo 2 de la Argentina, y sociedades científicas como la Asociación Estadounidense de Endocrinólogos Clínicos, Asociación Estadounidense de Diabetes y la Asociación Canadiense de Diabetes, recomiendan la metformina en caso de utilizar algún fármaco para pacientes con prediabetes y no mencionan el uso de inhibidores de DPP4 en esta población. La Asociación Latinoamericana de Diabetes establece tanto metformina como inhibidores de DPP4, entre otros fármacos, como tratamientos posibles en pacientes con prediabetes. La Administración Nacional de Medicamentos, Alimentos y Tecnología Médica de Argentina, la Administración de Medicamentos y Alimentos de los Estados Unidos y la Agencia Europea de Medicamentos, no aprobaron su uso en pacientes con prediabetes o síndrome metabólico. A su vez, diversos financiadores de salud de países de Europa y Estados Unidos cubren este fármaco en pacientes con DM tipo 2, pero no contemplan su uso en otras poblaciones, mientras que las entidades oficiales de la mayoría de los países de Latinoamérica no mencionan su cobertura para ninguna de estas indicaciones. No se encontraron estudios que evaluaran la costo-efectividad de los inhibidores de DPP4 en pacientes con prediabetes o síndrome metabólico sin diabetes mellitus. No se encontraron estudios que evaluaran la costo-efectividad de los inhibidores de DPP4 en pacientes con prediabetes o síndrome metabólico sin diabetes mellitus.

Healthcare resource utilization after initiation of sodium-glucose co-transporter-2 inhibitors versus dipeptidyl peptidase-4 inhibitors or other glucose-lowering drugs in Japanese patients with type 2 diabetes.

AIM: To examine healthcare resource utilization in type 2 diabetes (T2D) patients after initiation of sodium-glucose co-transporter-2 inhibitors (SGLT-2is) versus dipeptidyl peptidase-4 inhibitors (DPP-4is) or other glucose-lowering drugs (oGLDs). MATERIALS AND METHODS: A cost-utilization analysis was performed using a nationwide hospital-based administrative claims database (Medical Data Vision) during 2014-2018 in Japan, where universal healthcare coverage is maintained under a single-payer system. Data on T2D patients initiated on either SGLT-2is or oGLDs during the study period (228 514 patients) were extracted and subjected to a 1:1 propensity score-matching analysis (7626 patient pairs for DPP-4is and 28 484 for oGLDs). Direct healthcare resource utilizations and inpatient and outpatient costs were compared. RESULTS: After matching, baseline characteristics were well balanced, including healthcare costs within 3 and 12 months before the index date (standardized difference <5% for all variables), with a mean age of 61.6-64.1 years. While diabetes medication costs were higher in patients initiated with SGLT-2is than in those initiated with DPP-4is or oGLDs, further breakdown of individual cost components showed that SGLT-2is were associated with a lower hospitalization frequency and a shorter total hospital stay (by 213.0 or 204.6 days/100 patient-years compared with DPP-4is or oGLDs, respectively; P < .001). Accordingly, overall mean cumulative cost per patient at the 2.5-year postindex date was lower in patients with SGLT-2is than in those with DPP-4is or oGLDs by $2545 (1384.6-3759.7) and $2330 (1793.1-2882.9), respectively (P < .001). CONCLUSIONS: Our results show the benefits in healthcare resource utilization associated with SGLT-2i use in Japanese T2D patients.

Association of antidiabetic therapies with lower extremity amputation, mortality and healthcare cost from a nationwide retrospective cohort study in Taiwan.

We compared risks of clinical outcomes, mortality and healthcare costs among new users of different classes of anti-diabetic medications. This is a population-based, retrospective, new-user design cohort study using the Taiwan National Health Insurance Database between May 2, 2015 and September 30, 2017. An individual was assigned to a medication group based on the first anti-diabetic prescription on or after May 1, 2016: SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists or older agents (metformin, etc.). Clinical outcomes included lower extremity amputation, peripheral vascular disease, critical limb ischemia, osteomyelitis, and ulcer. We built three Cox proportional hazards models for clinical outcomes and mortality, and three regression models with a log-link function and gamma distribution for healthcare costs, all with propensity-score weighting and covariates. We identified 1,222,436 eligible individuals. After adjustment, new users of SGLT-2 inhibitors were associated with 73% lower mortality compared to those of DPP-4 inhibitors or users of older agents, while 36% lower total costs against those of GLP-1 agonists. However, there was no statistically significant difference in the risk of lower extremity amputation across medication groups. Our study suggested that SGLT-2 inhibitors is associated with lower mortality compared to DPP 4 inhibitors and lower costs compared to GLP-1 agonists.

Health care utilization and costs associated with switching from DPP-4i to GLP-1RA or SGLT2i: an observational cohort study.

BACKGROUND: Because of improved clinical outcomes, recent American Diabetes Association guidelines recommend the use of newer antidiabetic agents-glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i)-by those with cardiovascular disease. It is unclear, however, how switching to these newer agents affects health care utilization and costs. OBJECTIVE: To compare health care utilization and costs between users of dipeptidyl peptidase-4 inhibitors (DPP-4i) who switch to GLP-1RA or SGLT2i and nonswitchers. METHODS: We used claims data from a large pharmacy benefit manager. Patients included were commercially insured adults with type 2 diabetes and a prescription claim for DPP-4i in 2016 or 2017. Using propensity score methods, we matched patients who switched to SGLT2i or GLP-1RA with those who remained on DPP-4i. Among matched samples, we conducted multivariable negative binomial regression to examine differences in the incidence of inpatient and emergency room (ER) visits and generalized linear regression to examine differences in health care costs. RESULTS: Among 47,953 patients who used DPP-4i in 2016 and 2017, 507 switched to SGLT2i and 808 switched to GLP-1RA. Propensity score matching of 1:6 resulted in 3,042 nonswitchers/507 switchers for the SGLT2i cohort and 4,848 nonswitchers/808 switchers for the GLP-1RA cohort. Switchers to SGLT2i experienced a 39% reduction (incidence rate ratio [IRR] = 0.61, 95% CI = 0.38-0.96), and GLP-1RA switchers experienced a 29% reduction (IRR = 0.71, 95% CI = 0.52-0.97) in inpatient hospitalizations. ER visit rates did not differ significantly between switchers and nonswitchers. Switchers to SGLT2i did not have statistically significant differences in medical or pharmacy costs compared with DPP-4i users, while switchers to GLP-1RA had significantly higher total pharmacy costs (adjusted difference of $2,453.10, 95% CI = $1,837.20-$3,069.00). CONCLUSIONS: Switching from DPP-4i to GLP-1RA or SGLT2i was associated with fewer hospitalizations; however, higher pharmacy costs may outweigh savings from reduced hospitalizations, especially for GLP-1RAs. As newer diabetes guidelines steer specific populations to these drug classes, it is important to optimize drug pricing to realize their true value. DISCLOSURES: No outside funding supported this study. Neilson, Good, Swart, and Huang are employees of UPMC Center for Value-Based Pharmacy Initiatives and High-Value Care. Parekh reports employment at UPMC until July 2019. Munshi and Henderson are employed by Express Scripts. Newman has no disclosures to report.

Costs for commercially insured adults prescribed second-line diabetes medications.

OBJECTIVES: To examine differences in health care costs associated with choice of second-line antidiabetes medication (ADM) for commercially insured adults with type 2 diabetes. STUDY DESIGN: Retrospective cohort study with multiple pretests and posttests. METHODS: Included patients initiated second-line ADM therapy between 2011 and 2015, with variable follow-up through 2017. The 6 index medication classes were sulfonylureas, dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1 RAs), basal insulin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, and thiazolidinediones (TZDs). Multivariable regression models compared between-class changes in adjusted quarterly costs after second-line ADM initiation. RESULTS: The study cohort included 34,963 adults. Most were prescribed a sulfonylurea (46.0%) or DPP-4 inhibitor (30.4%). Adjusted quarterly index medication costs were significantly higher for all patients receiving nonsulfonylurea medications, ranging from $108 (95% CI, $99-$118) for TZDs to $742 (95% CI, $720-$765) for GLP-1 RAs. Changes in quarterly total health care costs were significantly higher for all nonsulfonylurea classes. Conversely, changes in quarterly nonpharmacy medical costs were significantly lower for patients receiving DPP-4 inhibitors (-$67; 95% CI, -$92 to -$43), GLP-1 RAs (-$43; 95% CI, -$85 to -$1), and SGLT-2 inhibitors (-$46; 95% CI, -$87 to -$6); changes in all other quarterly costs besides the index medication were significantly lower for patients receiving DPP-4 inhibitors (-$60; 95% CI, -$94 to -$26) and SGLT-2 inhibitors (-$113; 95% CI, -$169 to -$57). CONCLUSIONS: The higher cost of nonsulfonylurea medications was the main driver of relative increases in total costs. Relative decreases in nonpharmacy medical costs among patients receiving newer ADM classes reflect these medications' potential value.