Durability of Effectiveness Between Users of Once-Weekly Semaglutide and Dipeptidyl Peptidase 4 Inhibitors (DPP-4i) in US Adults with Type 2 Diabetes.

INTRODUCTION: Long-term effectiveness and durability of glucose-lowering medications are important considerations in managing type 2 diabetes (T2D). This study aimed to compare durability of treatment efficacy of once-weekly (OW) semaglutide for T2D with that of the dipeptidyl peptidase 4 inhibitor (DPP-4i) class. METHODS: This observational cohort study used 2017-2022 data from the Optum® Clinformatics® Data Mart to compare long-term clinical outcomes associated with semaglutide or DPP-4i in US adults with T2D. The primary outcomes were HbA1c at 2-year follow-up, change in HbA1c from baseline, and the odds of achieving HbA1c targets. BMI at 2-year follow-up, change in BMI from baseline, odds of reducing BMI category, and the need for treatment augmentation were exploratory outcomes. Bivariate and multivariate analyses were conducted using inverse probability of treatment weighting (IPTW) weighted descriptive statistics. RESULTS: Weighted HbA1c and BMI cohorts included 865 and 642 semaglutide users and 779 and 537 DPP-4i users, respectively. In the weighted HbA1c cohort, semaglutide and DPP-4i users had an average age of 60 years and similar baseline characteristics including HbA1c level and comorbidity status. Two-year follow-up HbA1c with semaglutide was 0.56% lower than with DPP-4i; reduction in HbA1c from baseline was 0.61% greater. Odds of achieving HbA1c level < 7% were 2.16 times greater after covariate adjustment (all, p < 0.001). Semaglutide was associated with 1.03 kg/m2 greater reduction in BMI and 2.27 times greater odds of reducing BMI category vs DPP-4i (p < 0.001). Semaglutide users were less likely to add new glucose-lowering treatment (hazard ratio [HR] 0.57; p < 0.001) or initiate insulin (HR 0.49; p < 0.001) vs DPP-4i users. CONCLUSION: Compared with DPP-4i, semaglutide was associated with lower follow-up HbA1c and BMI, greater reduction in HbA1c and BMI from baseline, and reduced likelihood of requiring treatment augmentation or insulin initiation to manage T2D in US adults, suggesting better durability of semaglutide vs DPP-4i. INFOGRAPHIC.

Type 2 diabetes (T2D) is a progressive disease. Over time, many patients with T2D will need multiple drugs to manage their disease. Long-term efficacy is important for achieving treatment goals, such as blood sugar control and weight loss. The amount of time that different types of diabetes drugs remain effective varies. This study used real-world data to compare two distinct types of diabetes drugs, semaglutide and dipeptidyl peptidase 4 inhibitors (DPP­4is). We looked at how blood sugar control and body weight changed with each drug after 2 years of use. We also compared how many patients needed to start using new drugs to meet their treatment goals and the odds that a patient would need to start using new drugs. Semaglutide was better than DPP­4i in reducing both blood sugar levels and body weight. Patients had over two times the odds of meeting target blood sugar levels with semaglutide. Fewer patients needed to start using new drugs with semaglutide, and patients were 43% less likely to start using new drugs to lower blood sugar than patients taking DPP­4is.

Once-weekly glucagon-like peptide-1 receptor agonists vs dipeptidyl peptidase-4 inhibitors: cardiovascular effects in people with diabetes and cardiovascular disease.

BACKGROUND: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), which have proven cardiovascular benefits, are recommended in people with type 2 diabetes (T2D) and atherosclerotic cardiovascular disease (ASCVD). However, there is limited real-world evidence comparing the effects of once-weekly (OW) GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4is). This observational cohort study (1/1/2017-9/30/2021) used data from the Optum Clinformatics® Data Mart to compare time to incident clinical cardiovascular outcomes, health care resource utilization (HCRU), and medical costs in new adult users of OW GLP-1 RAs and DPP-4is with T2D and ASCVD. METHODS: Time to occurrence of ischemic stroke, myocardial infarction (MI), or their composite and ASCVD-related and all-cause HCRU and medical costs were investigated. Baseline characteristics were balanced using inverse probability of treatment weighting. Survival analyses were conducted to compare risks during exposure. RESULTS: OW GLP-1 RA users (weighted N = 25,287) had 26%, 22%, and 24% lower risk of ischemic stroke, MI, and their composite, respectively, compared with DPP-4i users (weighted N = 39,684; all P < 0.01). Compared with DPP-4i users, OW GLP-1 RA users had 25% and 26% lower ASCVD-related and all-cause hospitalization costs, 19% and 23% lower ASCVD-related and all-cause medical costs, 23% and 27% fewer ASCVD-related and all-cause hospitalizations, 13% and 8% fewer ASCVD-related and all-cause outpatient visits, and 8% fewer all-cause ER visits (all P < 0.01). CONCLUSIONS: In adults with T2D and ASCVD, OW GLP-1 RAs are associated with reduced stroke and MI risks and ASCVD-related and all-cause HCRU and costs vs DPP-4is.

Increased Healthcare Resource Use and Costs After Discontinuation of Liraglutide in Patients with Type 2 Diabetes from a Commercial- and Medicaid-Insured Claims Database.

INTRODUCTION: Liraglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), is effective in patients with type 2 diabetes (T2D), but treatment discontinuation without new T2D therapy initiation may compromise outcomes. METHODS: This retrospective cohort study (July 1, 2012, to December 31, 2019) identified patients ≥ 18 years with T2D in the Optum® Clinformatics® Data Mart who discontinued liraglutide (index date). Patients with continuous enrollment for ≥ 12 months before and after discontinuation (baseline), ≥ 6 months liraglutide coverage pre-index, and no new T2D therapy start during follow-up were included. Changes from baseline in all-cause healthcare resource utilization (HCRU; outpatient visits, emergency room [ER] visits, and hospitalization events), costs, and glycated hemoglobin (HbA1c) over 12 months after discontinuation were evaluated. RESULTS: Overall, 625 of 186,630 patients who discontinued liraglutide during the baseline period (mean [standard deviation (SD)] age, 62.1 [10.1] years) were included in the 12-month analysis. A significant increase in the rate of ER visits (rate ratio [95% confidence interval (CI)]: 1.23 per 100 person-months [1.05, 1.43]; P = 0.0079), hospitalizations (1.36 [1.09, 1.70]; P = 0.0056), and outpatient visits (1.03 [1.01, 1.06]; P = 0.0075) was observed. Total HCRU costs significantly increased after discontinuation ($436.12 per patient per month [$90.07, $782.17]; P = 0.0136), driven by significantly higher outpatient costs ($238.70 [$34.16, $443.25]; P = 0.0223). HbA1c increased significantly by 12 months from mean (SD) 7.37 (1.53) at baseline to 7.63 (1.64; difference: + 0.25 [95% CI 0.14, 0.36]; P < 0.0001). CONCLUSIONS: Patients who discontinued liraglutide showed increases in HCRU; costs, mainly driven by outpatient cost; and HbA1c within 12 months, emphasizing the importance of treatment optimization on clinical and economic outcomes in patients with T2D.

Liraglutide is indicated in patients with type 2 diabetes and elevated cardiovascular risk or established cardiovascular disease. In this study, we observed that adults with type 2 diabetes who discontinued liraglutide showed increases in healthcare resource utilization; costs, which were mainly driven by increases in outpatient visits; and glycated hemoglobin within 12 months. In adults with type 2 diabetes, treatment discontinuation without restarting or initiating a new therapy impacts short-term healthcare resource utilization and economic outcomes, and future work may further investigate the long-term implications of sustained treatment discontinuation.

Impact of cardiovascular disease on health care economic burden and resource utilization: a retrospective cohort study in adults in the United States with type 2 diabetes with or without stroke, myocardial infarction, and peripheral arterial disease.

OBJECTIVES: To evaluate incidence of stroke, myocardial infarction (MI), and peripheral artery disease (PAD) in patients with type 2 diabetes mellitus (T2DM) and assess associated health care resource utilization (HCRU) and costs in the United States. METHODS: Patients ≥18 years of age with a T2DM diagnosis, with or without incident stroke/MI/PAD, were indexed between 1 January 2012 and 31 December 2020, from the deidentified Optum Clinformatics Data Mart claims database. Incidence of stroke, MI, and PAD was evaluated in the year following T2DM. HCRU and costs were measured in the 12 months following study entry in patients with T2DM + stroke, T2DM + MI, and T2DM + PAD (experimental cohorts) and compared to HCRU and costs in patients with T2DM alone (control cohorts). RESULTS: Incidence of stroke, MI, and PAD in patients with T2DM was 0.9% (n = 16,034), 0.7% (n = 13,681), and 4.1% (n = 68,479), respectively. Compared to matched patients with T2DM alone, patients with T2DM + stroke/MI/PAD had significantly higher total healthcare costs in the year post-index date (T2DM + stroke: +$5962 per patient per month [PPPM]; T2DM + MI: +$7932 PPPM; T2DM + PAD: +$2652 PPPM; p < .05). Patients with T2DM + stroke/MI/PAD had significantly higher mean HCRU than patients without stroke/MI/PAD in all categories measured. CONCLUSION: Having stroke, MI, or PAD was associated with increases in HCRU and costs in patients with T2DM. Although PAD was associated with smaller per patient increases in total healthcare costs than patients with T2DM + stroke/MI, the higher frequency of incident PAD may make it more costly than MI or stroke in a large population of patients with T2DM.

Compared to patients without type 2 diabetes (T2D), patients with T2D have a greater chance of having a stroke, heart attack, and narrowing of blood vessels in the arms and legs (peripheral artery disease [PAD]). A stroke, heart attack, or PAD may lead to hospitalization or death. We sought to understand healthcare usage (hospital visits, emergency room visits, office visits, etc.) and costs associated with stroke, heart attack, and PAD in patients with T2D in the United States. Healthcare resource usage and costs were estimated by using data from health insurance claims to compare healthcare usage and costs among patients with T2D, some of whom had a stroke, heart attack, or PAD, and some who did not. Compared to patients with T2D without stroke/heart attack/PAD, patients with T2D and stroke/heart attack/PAD had more overnight hospital visits, doctors' office visits, and emergency room visits. Patients with T2D and stroke/heart attack/PAD also had longer hospital stays. Patients with T2D and stroke/heart attack/PAD all had higher total healthcare costs in the year following their diagnoses, compared to patients with T2D without stroke/heart attack/PAD. By highlighting the greater costs and use of healthcare associated with stroke, heart attack, and PAD in patients with T2D, we hope to encourage more preventative management of stroke, heart attack, and PAD in patients with T2D.

Semaglutide Once-Weekly Persistence and Adherence Versus Other GLP-1 RAs in Patients with Type 2 Diabetes in a US Real-World Setting.

INTRODUCTION: The superior efficacy and safety of semaglutide once-weekly (QW), compared with dulaglutide, liraglutide, or exenatide QW, have been demonstrated in the SUSTAIN trials. This study assessed treatment persistence and adherence to semaglutide QW versus dulaglutide, liraglutide, or exenatide QW in a real-world setting. METHODS: This retrospective, database study used Optum's de-identified Clinformatics® Data Mart Database to identify glucagon-like peptide 1 receptor agonist (GLP-1 RA) treatment-naïve adult patients with type 2 diabetes (T2D) initiating semaglutide QW, dulaglutide, liraglutide, or exenatide QW between January 1, 2018 and April 30, 2019. Persistence (time remaining on treatment) was assessed with Kaplan-Meier survival estimates and Cox proportional hazard models. Adherence was assessed using proportion of days covered (PDC) and proportion of patients with PDC > 80%. RESULTS: Of 56,715 patients included, 3279 received semaglutide QW, 27,891 dulaglutide, 17,186 liraglutide, and 8359 exenatide QW. Patients initiating semaglutide QW were younger and with lower percentage of Medicare coverage than patients initiating the comparators. Persistence at 360 days was significantly higher for semaglutide QW (67.0%) versus dulaglutide (56.0%), liraglutide (40.4%), and exenatide QW (35.5%); p < 0.001 for all comparisons. Compared with semaglutide QW, the discontinuation rate was significantly higher for dulaglutide (hazard ratio [HR] 1.22; 95% confidence interval [CI] 1.13, 1.32; p < 0.001), liraglutide (HR 1.80; 95% CI 1.66, 1.95; p < 0.001), and exenatide QW (HR 2.12; 95% CI 1.96, 2.30; p < 0.001). Adherence to semaglutide QW versus liraglutide at 360 days and to exenatide QW was 39.1% versus 30.0% [p = 0.07] and 27.7% [p = 0.02], respectively. Adherence to dulaglutide at 360 days was numerically higher than semaglutide QW (43.2% versus 39.1%; p = 0.45) but did not reach statistical significance. CONCLUSION: Persistence with semaglutide QW was significantly greater than comparators, while adherence was comparable or greater. Together with earlier results from double-blind clinical studies, these data support semaglutide QW use for treatment of patients with T2D.

Decreasing incidence of type 2 diabetes mellitus in the United States, 2007-2012: Epidemiologic findings from a large US claims database.

AIMS: To explore epidemiological trends in type 2 diabetes mellitus (T2D) in the US between 2007 and 2012 using a large US claims database, with a particular focus on demographics, prevalence, newly-diagnosed cases, and comorbidities. METHODS: Truven Health MarketScan® Databases were used to identify patients with claims evidence of T2D in the years 2007 and 2012. Newly-diagnosed T2D was characterized by an absence of any T2D claims or related drug claims for 6months preceding the index claim. Demographic and comorbidity characteristics of the prevalent and new-onset T2D groups were compared and analyzed descriptively for trends over time. RESULTS: The overall prevalence of T2D remained stable from 2007 (1.24 million cases/15.07 million enrolled; 8.2%) to 2012 (2.04 million cases/24.52 million enrolled; 8.3%), while the percentage of newly-diagnosed cases fell dramatically from 2007 (152,252 cases; 1.1%) to 2012 (147,011 cases; 0.65%). The mean age of patients with prevalent T2D was similar in 2007 (60.6y) and 2012 (60.0y), while the mean age of newly-diagnosed T2D patients decreased by 3years from 2007 (57.7y) to 2012 (54.8y). Hypertension and hyperlipidemia were the most common comorbidities, evident in 50-75% of T2D patients, and increased markedly from 2007 to 2012 in both prevalent and new-onset T2D populations. Cardiovascular disease decreased slightly in prevalent (-0.9%) and new-onset (-2.8%) cases. CONCLUSIONS: This large US health claims database analysis suggests stabilization in prevalence and declining incidence of T2D over a recent 5-year period, a downward shift in age at T2D diagnosis, but increases in several comorbidities.

Longitudinal Changes in Medical Services and Related Costs in a Single Cohort of Patients Newly Diagnosed With Type 2 Diabetes, 2006 to 2012.

PURPOSE: Documenting diabetes treatment patterns and associated costs over time is an important step in gauging the medical and economic impact of current treatment guidelines in a real-world setting. This study was designed to assess changes in medication treatment patterns, health care costs, and comorbidities over a 6-year period after a new diagnosis of type 2 diabetes mellitus (T2DM). This analysis is the first of its kind to observe, over time, a single US cohort of patients newly diagnosed with T2DM. METHODS: This study was a longitudinal assessment of changes in medical services and comorbidities for a single cohort (N = 35,017) of adults newly diagnosed with T2DM in 2006 using claims data from Truven Health Analytics MarketScan(®) databases. Prevalence of diabetes-related comorbidities and utilization/costs of inpatient/outpatient services and medications were analyzed annually for the index (diagnosis) year (Y1) through year 6 (Y6) postindex. Costs were adjusted to 2012 dollars. FINDINGS: From Y1 to Y6, increased prevalence was noted for several T2DM-associated comorbidities: cerebrovascular disease (13%-21%), peripheral vascular disease (3%-10%), nephropathy (3%-13%), and retinopathy (4%-14%). All-cause costs of inpatient and outpatient services and medications were analyzed for the index year (Y1) through Y6 postindex (adjusted to 2012 dollars). Total health care utilization costs (services plus drugs) increased by 33.3% from Y1 ($329.8 million) to Y6 ($439.5 million). Inpatient costs across the entire cohort increased 19.3% from Y1 ($49.8 million; $1421/patient) to Y6 ($59.4 million; $1695/patient) but increased 46.6% among utilizers, despite a decline in inpatient utilizers (7.3% to 5.9% of patients). The percentage of outpatient services utilizers remained stable (Y1, 98.2%; Y6, 97.2%), but total visits increased by 9.1%. Costs of outpatient services increased by 32.5%, from $145 million (Y1) to $192 million (Y6). Total drug costs increased from $101.5 million (Y1) to $114.7 million (Y6) but accounted for a smaller percentage of all health care costs in Y6 versus Y1 (26.1% vs 30.7%). Antidiabetes drugs accounted for a small percentage of overall costs in both Y1 (3.6%) and Y6 (5.3%). IMPLICATIONS: Overall, we found evidence of increasing comorbidities paralleled by large increases in costs for medical services but less for prescriptions. These findings confirm a need for aggressive diabetes management to slow disease progression and minimize comorbidity and economic burdens of the disease.

Trends in the incidence of diabetes, its clinical sequelae, and associated costs in pregnancy.

BACKGROUND: Increasing diabetes prevalence affects a substantial number of pregnant women in the United States. Our aims were to evaluate health outcomes, medical costs, risks and types of complications associated with diabetes in pregnancy for mothers and newborns. METHODS: In this retrospective claims analysis, patients were identified from the Truven Health MarketScan(®) database (2004-2011 inclusive). Participants were aged 18-45 years, with ascertainable diabetes status [Yes/No], date of birth event >2005 and continuous health plan enrolment ≥21 months before and 3 months after the birth. RESULTS: In total, 839 792 pregnancies were identified, and 66 041 (7.86%) were associated with diabetes mellitus [type 1 (T1DM), 0.13%; type 2 (T2DM), 1.21%; gestational (GDM), 6.29%; and GDM progressing to T2DM (patients without prior diabetes who had a T2DM diagnosis after the birth event), 0.23%]. Relative risk (RR) of stillbirth (2.51), miscarriage (1.28) and Caesarean section (C-section) (1.77) was significantly greater with T2DM versus non-diabetes. Risk of C-section was also significantly greater for other diabetes types [RR 1.92 (T1DM); 1.37 (GDM); 1.63 (GDM progressing to T2DM)]. Risk of overall major congenital (RR ≥ 1.17), major congenital circulatory (RR ≥ 1.19) or major congenital heart (RR ≥ 1.18) complications was greater in newborns of mothers with diabetes versus without. Mothers with T2DM had significantly higher risk (RR ≥ 1.36) of anaemia, depression, hypertension, infection, migraine, or cardiac, obstetrical or respiratory complications than non-diabetes patients. Mean medical costs were higher with all diabetes types, particularly T1DM ($27 531), than non-diabetes ($14 355). CONCLUSIONS: Complications and costs of healthcare were greater with diabetes, highlighting the need to optimize diabetes management in pregnancy.

Diabetes management in the real world and the impact of adherence to guideline recommendations.

OBJECTIVE: To evaluate diabetes management in the real world, examining adherence to the American Diabetic Association (ADA) guidelines on frequency of glycated hemoglobin A1c (A1C) testing and antidiabetic treatment modifications in patients with type 2 diabetes and measuring the impact of adherence to the guidelines for achieving an A1C target <7%. RESEARCH DESIGN AND METHODS: Retrospective analyses of claims data were conducted in three groups of patients aged ≥18 years with at least two diagnoses of type 2 diabetes in a large US health insurance claims database between January 2009 and December 2011 and with A1C ≥7% (≥53 mmol/mol). Descriptive analyses were performed on adherence to A1C testing frequency and adherence to antidiabetic treatment modification. Pearson's chi-square test and logistic regression were conducted to estimate the odds ratios. RESULTS: Of 42,837 patients evaluated for adherence to the ADA guideline for A1C testing frequency, only 7% were fully adherent for 1 year. Analysis of 95,330 patients for adherence to antidiabetic treatment modification revealed that drug therapy was modified in accordance with ADA guidelines for 39% of patients. Among 1337 treatment-naive patients meeting the selection criteria, only 3% met both testing frequency and treatment modification guidelines; the odds of achieving the A1C target of <7% were approximately five-fold higher in patients who met both guidelines versus those who did not (odds ratio 5.29; P < 0.0001). CONCLUSIONS: This study, based on real-world data from a large type 2 diabetes patient population, demonstrated that adherence to ADA guidelines for A1C testing frequency and drug treatment modifications was extremely low. Achievement of glycemic control (A1C <7%) was significantly associated with adherence to both A1C testing frequency and antidiabetic treatment modification guidelines. Limitations of this study include the retrospective nature, lack of important patient clinical information, and issues with incomplete source data.

Algae biodiesel - a feasibility report.

BACKGROUND: Algae biofuels have been studied numerous times including the Aquatic Species program in 1978 in the U.S., smaller laboratory research projects and private programs. RESULTS: Using Molina Grima 2003 and Department of Energy figures, captial costs and operating costs of the closed systems and open systems were estimated. Cost per gallon of conservative estimates yielded $1,292.05 and $114.94 for closed and open ponds respectively. Contingency scenarios were generated in which cost per gallon of closed system biofuels would reach $17.54 under the generous conditions of 60% yield, 50% reduction in the capital costs and 50% hexane recovery. Price per gallon of open system produced fuel could reach $1.94 under generous assumptions of 30% yield and $0.2/kg CO2. CONCLUSIONS: Current subsidies could allow biodiesel to be produced economically under the generous conditions specified by the model.