Noninsulin Antidiabetic Medications Research Articles

Association between Diabetes Status and Long-term Outcomes Following Open and Endovascular Repair of Infrarenal Abdominal Aortic Aneurysms

Current literature reports conflicting findings regarding the effect of diabetes mellitus (DM) on outcomes of abdominal aortic aneurysm (AAA) repair. In this study we examined the effect of DM and its management on outcomes after open AAA repair (OAR) and endovascular AAA repair (EVAR). We identified all patients undergoing OAR or EVAR for infrarenal AAA between 2003 and 2018 in the Vascular Quality Initiative registry data linked with Medicare claims. We excluded patients with missing DM status. Patients were stratified by their preoperative DM status, and then further stratified by DM management: dietary, noninsulin antidiabetic medications (NIMs), or insulin. Outcomes of interest included 1-year aneurysm sac dynamics, 8-year aneurysm rupture, reintervention, and all-cause mortality. These outcomes were analyzed with the χ2 test, Kaplan-Meier methods, and multivariable Cox regression analyses. We identified 34,021 EVAR patients and 4127 OAR patients, of whom 20% and 16% had DM, respectively. Of all DM patients, 22% were managed by dietary management, 59% by NIM, and 19% by insulin. After EVAR, DM patients were more likely to have stable sacs, whereas non-DM patients were more likely to have sac regression at 1year. Compared with non-DM, DM was associated with a significantly lower risk for 8-year rupture in EVAR (EVAR hazard ratio [HR], 0.68; 95% confidence interval [CI], 0.51-0.92). Compared with non-DM, NIM was associated with lower risk of rupture within 8-years for both EVAR and OAR (EVAR HR, 0.64; 95% CI, 0.44-0.94; OAR HR, 0.29; 95% CI, 0.41-0.80), whereas dietary control and insulin had a similar rupture risk compared with non-DM. However, compared with non-DM, DM was associated with a higher risk of 8-year all-cause mortality after EVAR and OAR (DM vs non-DM: EVAR HR, 1.17; 95% CI, 1.11-1.23; OAR HR, 1.16; 95% CI, 1.00-1.36). After further DM management substratification, compared with non-DM, management with NIM and insulin were associated with a higher 8-year mortality in EVAR and OAR (EVAR: NIM HR, 1.12; 95% CI, 1.05-1.20; insulin: HR, 1.40; 95% CI, 1.26-1.55; OAR: NIM HR, 1.27; 95% CI, 1.06-1.54; and insulin: HR, 1.57; 95% CI, 1.15-2.13). Finally, there was a similar risk of reintervention across the DM and non-DM populations for EVAR and OAR. DM was associated with a lower adjusted risk of rupture after EVAR as well as OAR in patients managed with NIM. Nevertheless, just as in patients without AAA, preoperative DM was associated with a higher adjusted risk of all-cause mortality. Further study is needed to evaluate for differences in aneurysm-related mortality between DM and non-DM patients, and studies are planned to evaluate the independent effect of NIM on aneurysm-related outcomes.

Assessment of Cardiovascular Risk Categories and Achievement of Therapeutic Targets in European Patients with Type 2 Diabetes.

Background: Individuals diagnosed with type 2 diabetes mellitus (T2DM) are more prone to experiencing severe cardiovascular (CV) events, often occurring at a younger age, due to a complex interplay of risk factors. T2DM diagnosis inherently classifies patients as belonging to a higher CV risk group. In light of the increased susceptibility to severe CV outcomes, our study aims to assess the distribution of CV risk categories and the attainment of therapeutic targets among Romanian patients diagnosed with T2DM. Methods: A cross-sectional analysis was performed, including 885 patients diagnosed with T2DM who were consecutively admitted to a secondary care hospital unit between January and July 2019. Data collection included demographics, lipid profile, glycated hemoglobin (HbA1c), blood pressure (BP), estimated glomerular filtration rate (eGFR), and medication specifics for T2DM and associated conditions. Patients were stratified into CV risk categories based on the ESC/EAS guidelines, encompassing moderate, high, and very high risk categories. The rationale for selecting these guidelines for CV risk categories was that they were current and provided best practice recommendations for T2DM patients during the cross-sectional evaluation. We assessed therapeutic target achievement rates for LDL-C, HbA1C, and BP for each CV risk category. Additionally, we examined utilization rates of statins and novel cardio- and reno-protective, non-insulin antidiabetic medications. Results: The group's average age was 62.9 ± 7.7 years and comprised 53.7% females. An average HbA1c level of 7.1 ± 1.3% was observed in the group. Within the cohort, 83% had hypertension, with a mean systolic BP of 132 ± 16.2 mm Hg and mean diastolic BP of 80 ± 9.6 mm Hg. Additionally, 64.6% of patients were obese, with a mean body mass index of 32.3 ± 5.3 kg/m2. Mean LDL-C levels varied across the different CV risk categories: 106.6 ± 35.6 mg/dL in the very high risk category, 113 ± 39.3 mg/dL in the high risk category, and 124.3 ± 38.3 mg/dL in the moderate risk category. Most treatment schemes included metformin (87.0%) and statins (67.0%), with variable use rates for other glucose-lowering and CV risk-modifying therapies. The percentage of patients using GLP-1 RAs was 8.1%, while 3.9% used SGLT2 inhibitors. Conclusions: Most Romanian patients with T2DM are at very high or high CV risk. Despite reaching glycemic control targets, most patients are not achieving the composite target, which includes, besides glycemic control, BP values and lipid profile. Many patients with T2DM are not benefiting from DM therapies with additional cardiorenal benefits or statins.

Safety of GLP-1 Receptor Agonists and Other Second-Line Antidiabetics in Early Pregnancy

Increasing use of second-line noninsulin antidiabetic medication (ADM) in pregnant individuals with type 2 diabetes (T2D) may result in fetal exposure, but their teratogenic risk is unknown. To evaluate periconceptional use of second-line noninsulin ADMs and whether it is associated with increased risk of major congenital malformations (MCMs) in the infant. This observational population-based cohort study used data from 4 Nordic countries (2009-2020), the US MarketScan Database (2012-2021), and the Israeli Maccabi Health Services database (2009-2020). Pregnant women with T2D were identified and their live-born infants were followed until up to 1 year after birth. Periconceptional exposure was defined as 1 or more prescription fill of sulfonylureas, dipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists, and sodium-glucose cotransporter 2 (SGLT2) inhibitors, or insulin (active comparator) from 90 days before pregnancy to end of first trimester. Relative risks (RRs) and 95% CIs for MCMs were estimated using log-binomial regression models, adjusting for key confounders in each cohort and meta-analyzed. Periconceptional exposure to second-line noninsulin ADMs differed between countries (32, 295, and 73 per 100 000 pregnancies in the Nordics, US, and Israel, respectively), and increased over the study period, especially in the US. The standardized prevalence of MCMs was 3.7% in all infants (n = 3 514 865), 5.3% in the infants born to women with T2D (n = 51 826), and among infants exposed to sulfonylureas was 9.7% (n = 1362); DPP-4 inhibitors, 6.1% (n = 687); GLP-1 receptor agonists, 8.3% (n = 938); SGLT2 inhibitors, 7.0% (n = 335); and insulin, 7.8% (n = 5078). Compared with insulin, adjusted RRs for MCMs were 1.18 (95% CI, 0.94-1.48), 0.83 (95% CI, 0.64-1.06), 0.95 (95% CI, 0.72-1.26), and 0.98 (95% CI, 0.65-1.46) for infants exposed to sulfonylureas, DPP-4 inhibitors, GLP-1 receptor agonists, and SGLT2 inhibitors, respectively. Use of second-line noninsulin ADMs is rapidly increasing for treatment of T2D and other indications, resulting in an increasing number of exposed pregnancies. Although some estimates were imprecise, results did not indicate a large increased risk of MCMs above the risk conferred by maternal T2D requiring second-line treatment. Although reassuring, confirmation from other studies is needed, and continuous monitoring will provide more precise estimates as data accumulate.

Evaluation of outpatient health services in diabetes mellitus in a middle-income setting: a retrospective cohort study involving secondary care

In Brazil, it is necessary to assess the different levels of health care in diabetes mellitus (DM) in order to integrate them. In this retrospective cohort study, we analyzed 1,122 medical records of patients with DM from specialized services with interdisciplinary health teams (IHT) in the city of Ourinhos, São Paulo state, Brazil, to assess the impact of secondary care on glycemic control in patients with DM in those places and to compare baseline and follow-up DM care indicators concerning clinical evaluation and drug treatment regimens in the aforementioned health services. The study covered consultations carried out from September/2013 to September/2017. Data were collected from initial and final appointments in medical records and revealed an increase of 31.21% in insulin introduction and of 73.53% in regimens with three or more non-insulin antidiabetic (NIA) medications. Among the 570 patients with at least two glycated hemoglobin (A1C) measurements in the aforementioned review, 146 did not require any therapeutic adjustment between initial and final appointments, 123 required a subtle adjustment, 95, a moderate adjustment, and 206, an intense adjustment. There was a noticeably higher A1C reduction between initial and final appointments when patients who required an intense drug adjustment were compared to those who did not need any different NIA drug (p-value < 0.0001). In addition to optimizing drug treatment, essential exams in DM were performed with higher frequency, with an increase of 63% in ophthalmology evaluation performed during secondary care approach and 60.65% more individuals being screened for diabetic chronic kidney disease. IHT secondary care considered in this study, therefore, not only improved glycemic control of patients with DM, especially by optimization of NIA regimens and timely prescription of insulin, but also increased the screening for microvascular complications.

88-LB: The Microvascular Effects of the Noninsulin Standard Antidiabetic Medications—A Literature Systemic Review of Randomised Controlled Clinical Studies

Backgrounds: As many advances have been made in recent decades in the understanding of the pathophysiology of diabetic macrovascular complications and novel pharmacological approach, few investigations on the importance and how the hypoglycemic medications that are currently available in reducing diabetic microvascular complications, though this amelioration can be achieved via intensive glycemic control such as insulin therapy. This study reviews the implications of diabetic microvascular complications by non-insulin antidiabetic medications. Methods: We searched and screened the literature of randomized clinical trials that reported the effects of drugs on diabetic microvascular complications, including diabetic nephropathy (DN), diabetic peripheral neuropathy (DPN), diabetic retinopathy (DR) from multiple clinical databases. We extracted the indices of estimated glomerular filtration rate (eGFR) and urinary albumin to creatinine ratio (UACR) or urinary albumin excretion rate (UAE), and indices for DPN or DR. Comparisons were made between certain classes of non-insulin antidiabetic medications. Main Results: The analyses showed the urinary albumin to creatinine ratio (UACR) or urinary albumin excretion rate (UAE) showed variations in both the effects and significance of the decline. In addition, due to the unavailable of a unified standard metric index on DPN or DR, we compiled different common measures on the DPN or DR, and also found disparities in both the effect and significance of each medication. Conclusions: Till now, all the reviewed non-insulin hypoglycemic medications showed different degrees of preventing diabetic microvascular complications. As emerging or ongoing trials will reveal the implications of diabetic microvascular prevention, more results with higher quality in comparative efficacy between different classes of non-insulin antidiabetic medications could serve as more powerful evidence for recommendation and utilized in clinical personalized treatment practices. Disclosure S. Wen: None. Funding Fudan Zhangjiang Clinical Medicine Innovation Fund Project (KP0202118)

Evaluating Pharmacist-Driven Interventions in a Primary Care Setting to Improve Proportion of Days Covered and Medication Adherence

Background: Medication nonadherence is the leading cause of poor health outcomes and increased risk of hospitalizations. Previous studies have shown that pharmacist interventions can help improve medication adherence and CMS quality measures. Objective: The purpose of this study was to examine the impact of clinical pharmacists’ interventions on medication adherence and PDC scores for ACEi/ARBs, statins, and noninsulin antidiabetic medications in the primary care setting. Methods: This observational study was conducted at four primary care clinics to evaluate PDC scores pre- and post-pharmacist interventions from April 2020 to December 2020. Eligible patients were Humana Part D beneficiaries with a baseline PDC score <85%. The primary outcome of this study was to evaluate the average change in final PDC scores, and 1-month change in PDC scores following a pharmacist intervention. Secondary outcomes were number and types of adherence barriers identified, interventions provided by the pharmacist, and barriers and interventions category (pharmacy, patient or physician-related). Results: A total of 89 barriers were identified and 208 interventions were completed. A statistically significant difference in the average change of final PDC score from baseline was seen among those on ACEi/ARBs (72.5 to 78.0, p = 0.004) and statins (73.3 to 76.6, p < 0.001). Similarly, a statistically significant change was observed from baseline to 1-month PDC among those on ACEi/ARBS (72.5 to 75.4, p = 0.001) and statins (73.3 to 74.9, p < 0.001). Conclusion: Pharmacists located in a primary care setting improved medication adherence and PDC score for patients on ACEIs/ARBs and statins.

Abstract TP133: Diabetes/hyperglycemia Is Associated With Poor Six-month Functional Outcomes, But Is Not Associated With The Development Of Microvascular Ischemic Lesions After Intracerebral Hemorrhage

Introduction: Ischemic lesions seen on diffusion weighted imaging (DWI) are associated with worsened outcomes after intracerebral hemorrhage (ICH) and are thought to arise due to microvascular damage. While hyperglycemia and diabetes mellitus contribute to small vessel disease, it is not known if these factors contribute to the development of DWI lesions and associated outcomes after ICH. Hypothesis: Indicators of diabetes/hyperglycemia will be associated with the development of DWI lesions and poor outcomes after ICH Methods: 1123 patients with MRI data from the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study were included. Predictors with p&lt;0.15 in univariate analyses were included in initial multivariable logistic regression models. Least absolute shrinkage and selection operator (LASSO) regression was used to identify final models. Results: In univariate analysis, no measure of diabetes or hyperglycemia (medical history of diabetes, insulin or non-insulin antidiabetic medication use, blood glucose obtained by emergency medical services, blood glucose on admission, fasting blood glucose, or hemoglobin A1c) was associated with the development of DWI lesions (p&gt;0.05). Blood glucose on admission was incorporated into the initial multivariable model (p&lt;0.15). Univariate analysis for poor six-month functional outcome (modified Rankin Score &gt;3) showed that history of diabetes (p&lt;0.001), blood glucose on admission (p=0.002), fasting blood glucose (p=0.049), and use of non-insulin antidiabetic medications (p=0.036) were associated with poor outcomes. Final multivariable logistic regression analyses are shown in Tables 1 and 2. Conclusions: While diabetes and hyperglycemia are associated with worsened outcomes after ICH, this relationship is unexpectedly not mediated by microinfarcts despite their association with cerebral small vessel disease.

Effects of a 6-month, low-carbohydrate diet on glycaemic control, body composition, and cardiovascular risk factors in patients with type 2 diabetes: An open-label randomized controlled trial.

To investigate the efficacy and safety of a non-calorie-restricted low-carbohydrate diet (LCD) on glycaemic control, body composition, and cardiovascular risk factors in patients with type 2 diabetes (T2D) instructed to maintain their non-insulin antidiabetic medication and physical activity. In an open-label randomized controlled trial, patients with T2D were randomized 2:1 to either a LCD with a maximum of 20 E% (percentage of total energy intake) from carbohydrates (n=49) or a control diet with 50-60 E% from carbohydrates (n=22) for 6 months. Examinations at enrolment and after 3 and 6 months included blood sample analyses, anthropometrics, blood pressure, accelerometer-based assessment of physical activity, and food diaries. Total fat mass and lean mass were determined by dual-energy x-ray absorptiometry scan. The mean difference in change between groups from baseline are reported. The LCD group decreased carbohydrate intake to 13.4 E% and increased fat intake to 63.2 E%, which was -30.5 ± 2.2 E% lower for carbohydrates and 30.6 ± 2.2 E% higher for fat, respectively, compared with the control group (all P < .001). The LCD reduced HbA1c after 3months (-8.9 ± 1.7 mmol/mol; P < .0001), and this was maintained after 6months (-7.5 ± 1.8 mmol/mol; P < .0001) compared with the control diet. The LCD also reduced weight (-3.9 ± 1.0kg), body mass index (-1.4 ± 0.4kg/m2 ), and waist circumference (-4.9 ± 1.3cm) compared with the control diet (all P < .01), accompanied by reductions in total fat mass (-2.2 ± 1.0kg; P=.027) and lean mass (-1.3 ± 0.6kg; P=.017). No changes in blood lipids or blood pressure were seen after 6months. The level of physical activity was maintained, and there were no episodes of severe hypoglycaemia. A non-calorie-restricted LCD high in fat has significant beneficial effects on glycaemic control and body composition, and does not adversely affect cardiovascular risk factors in patients with T2D. Reducing carbohydrate intake to 10-25 E% appears to be an effective and safe nutritional approach with respect to classical cardiovascular risk factors and hypoglycaemia.

Differences in Diabetic Prescription Drug Utilization and Costs Among Patients With Diabetes Enrolled in Colorado Marketplace and Medicaid Plans, 2014-2015

Increasing prices of antidiabetic medications in the US have raised substantial concerns about the effects of drug affordability on diabetes care. There has been little rigorous evidence comparing the experiences of patients with diabetes across different types of insurance coverage. To compare the utilization patterns and costs of prescription drugs to treat diabetes among low-income adults with Medicaid vs those with Marketplace insurance in Colorado during 2014 and 2015. This cross-sectional study included diabetic patients enrolled in Colorado Medicaid and Marketplace plans who were aged 19 to 64 years and had incomes between 75% and 200% of the federal poverty level during 2014 and 2015. Data analysis was conducted from September 2020 to April 2021. Health insurance through Colorado Medicaid or Colorado's state-based Marketplace. Primary outcomes were drug utilization (prescription drug fills) and drug costs (total costs and out-of-pocket costs). The secondary outcome was months with an active prescription for noninsulin antidiabetic medications. An all payer claims database was combined with income data, and linear models were used to adjust for clinical and demographic confounders. Of 22 788 diabetic patients included in the study, 20 245 were enrolled in Medicaid and 2543 in a Marketplace plan. Marketplace-eligible individuals were older (mean [SD] age, 52.12 [10.60] vs 47.70 [11.33] years), and Medicaid-eligible individuals were more likely to be female (12 429 [61.4%] vs 1413 [55.6%]). Medicaid-eligible patients were significantly more likely than Marketplace-eligible patients to fill prescriptions for dipeptidyl peptidase 4 inhibitors (adjusted difference, -3.7%; 95% CI, -5.3 to -2.1; P < .001) and sulfonylureas (adjusted difference, -6.6%; 95% CI, -8.9 to -4.3; P < .001). Overall rates of insulin use were similar in the 2 groups (adjusted difference, -2.3%; -5.1 to 0.5; P = .11). Out-of-pocket costs for noninsulin medications were 84.4% to 95.2% lower and total costs were 9.4% to 54.2% lower in Medicaid than in Marketplace plans. Out-of-pocket costs for insulin were 76.7% to 94.7% lower in Medicaid than in Marketplace plans, whereas differences in total insulin costs were mixed. The percentage of months of apparent active medication coverage was similar between the 2 groups for 4 of 5 drug classes examined, with Marketplace-eligible patients having a greater percentage of months than Medicaid-eligible patients for sulfonylureas (adjusted difference, 5.3%; 95% CI, 0.3%-10.4%; P = .04). In this cross-sectional study, drug utilization across multiple drug classes was higher and drug costs were significantly lower for adults with diabetes enrolled in Medicaid than for those with subsidized Marketplace plans. Patients with Marketplace coverage had a similar percentage of months with an active prescription as patients with Medicaid coverage.

Outpatient management of endocrine conditions during the COVID-19 pandemic

Still very active COVID-19 pandemic demands continuous adjustment of our regular practices of delivering patient care. The aim of this manuscript is to provide practical suggestions for the management of the most common endocrinological conditions during ongoing COVID-19/SARS-CoV2 pandemic. We have conducted a literature review and present our own experience of treating endocrinology patients during the months of full COVID-19 lockdown and then phased partial reopening. The results of the literature review have demonstrated the utmost importance of excelling in a challenging task of maintaining the best possible control of such endocrinological conditions as diabetes mellitus and adrenal insufficiency, while also maintaining the universal social distancing and isolation. In the patients with diabetes mellitus Hemoglobin A1C level correlates with the risk of unfavorable outcomes of COVID-19 which makes optimization of diabetes mellitus control an even more significant during the pandemic. It is important to provide the patients with the specific instructions on self-titration of insulin and on the use of non-insulin antidiabetic medications, examples of which are shown in the manuscript. For the patients with adrenal insufficiency, it is essential to discuss the rules of dose increase of the glucocorticosteroids in case of development of COVID-19 or any other acute illness. The diagnosis and management of other endocrinological conditions as for example thyroid nodules and osteoporosis (with the exclusion of secondary osteoporosis associated with diseases requiring timely treatment) can be delayed for the sake of everybodys safety and partially also for prioritization of healthcare recourses utilization during these uneasy times. Since the beginning of the pandemic a considerable amount of new information regarding theoretical and practical aspects of connection of SARS-CoV2 and endocrinology is emerging almost weekly. In this manuscript, we have tried to gather the most clinically relevant data on the outpatient management of the patients with endocrine pathology.

Evaluating the relationship between quality measure adherence definitions and economic outcomes in commercial health plans: a retrospective diabetes cohort study.

BACKGROUND: Diabetes is a prevalent chronic condition in the United States that results in considerable morbidity and mortality, frequent use of the health care system, and high health care expenditures. Adherence to antidiabetic medications can help improve health outcomes and lower health care utilization and expenditures. The Pharmacy Quality Alliance (PQA) Proportion of Days Covered (PDC): Diabetes All Class medication adherence measure was developed and endorsed to improve adherence to noninsulin antidiabetic medications; however, it has not been assessed in a commercial population of diabetes patients over a 1-year time frame. OBJECTIVE: To determine the association between adherence, as defined in the PQA medication adherence measures, and health care utilization and expenditure among commercially insured individuals using antidiabetic medications. METHODS: This 1-year retrospective study evaluated a cohort of individuals from IBM MarketScan Research Databases (2009-2015) with noninsulin antidiabetic medications. Eligible study subjects included adults (aged ≥ 18 years at index date) with continuous enrollment in their health plans for 6 months before (i.e., baseline period) and 12 months after (i.e., study period) the index date and ≥ 2 prescriptions dispensed for any medication included in the PQA PDC Diabetes All Class medication adherence measure, with at least 150 days between the first and last fill during the study period. The index date was defined as the first fill for a medication included in the PQA PDC Diabetes All Class adherence measure after a 180-day baseline period. Generalized linear models with log link and gamma distribution (expenditure) or negative binomial distribution (utilization) assessed relationships between adherence (≥ 80% PDC) and health care utilization and expenditure while adjusting for potential confounders. Cost ratios (CR) and rate ratios (RR) were computed using beta coefficients. Cohort characteristics were compared using t-tests, Wilcoxon rank sum tests, or chi-square tests with an alpha level of 0.001 set a priori. RESULTS: A total of 1,576,112 individuals were eligible; of these, 1,028,176 (65.2%) were adherent. Significant differences in demographic characteristics were observed between adherent and nonadherent groups (P < 0.001). Multivariable analyses demonstrated that adherence was associated with the following: (a) 16.6% fewer inpatient (RR = 0.834, 95% CI = 0.819-0.850) and 3.6% more outpatient service visits (RR = 1.036, 95% CI = 1.032-1.039) and (b) 16.8% lower inpatient expenditures (CR = 0.833, 95% CI = 0.829-0.836); 2.6% lower outpatient expenditures (CR = 0.974, 95% CI = 0.970-0.978); 16.4% higher prescription drug expenditures (CR = 1.164, 95% CI = 1.159-1.169); and 4.2% lower total (CR = 0.958, 95% CI = 0.954-0.962) expenditures. Adherent subjects were associated with lower incremental per member per month expenditures for inpatient (-$31.74), outpatient (-$10.09), and total (-$30.82) expenditures, yet higher prescription drug expenditures ($25.60) compared with nonadherent subjects. CONCLUSIONS: Adherence to noninsulin antidiabetic medications was associated with more outpatient and fewer inpatient visits, as well as lower total expenditures compared with nonadherence. DISCLOSURES: Funding was provided by grants from Pharmacy Quality Alliance, Merck & Co. (Kenilworth, NJ), and SinfoniaRx. In addition, Chinthammit reports personal fees from Eli Lilly and Company, outside the submitted work. Axon reports grants from the American Association of Colleges of Pharmacy and the Arizona Department of Health Services, outside the submitted work. Taylor reports grants from the Arizona Department of Health Services, outside the submitted work. Warholak reports grants from Novartis and the Arizona Department of Health Services, outside the submitted work. Chinthammit and Campbell disclose that this work was completed during their employment at the University of Arizona. This research was presented as a poster at the AMCP Annual Meeting 2019; March 25-28, 2019; San Diego, CA.

Antidiabetic medication use in commercially insured children and adolescents in the United States from 2004 to 2019.

To describe the patterns of non-insulin antidiabetic medication use, initiation and adherence in the paediatric population. We conducted a descriptive study of non-insulin antidiabetic medication use in children and adolescents (aged 10-18 years) using real-world data from a nationwide US commercial claims database (January 2004-September 2019). Trends in the prevalence of non-insulin antidiabetic medication use overall and by class were evaluated. Among new users of non-insulin antidiabetic agents, medication adherence was examined using group-based trajectory models. In a cohort of more than 1 million paediatric patients, the prevalence of any non-insulin antidiabetic medication use was 75.7 per 100 000 patients in 2004 and more than doubled to 162.0 per 100 000 in 2019. Biguanides (metformin) was by far the most widely used medication class. The use of newer classes was low (<10 per 100 000), but there was an uptake in the use of glucagon-like peptide-1 receptor agonists after liraglutide received paediatric approval in 2019. Medication adherence was poor during the 18 months after treatment initiation: 79.6% of initiators experienced an early treatment interruption (median time to interruption: 90 days among metformin monotherapy initiators) and 21% of initiators did not return for a prescription refill after the first month. There was a substantial increase in non-insulin antidiabetic medication use among commercially insured paediatric patients from 2004 to 2019. Nearly all patients were treated with metformin, while the use of newer agents remained low. Despite the increase in medication use, short treatment episodes were observed, even among patients with a diagnosis of type 2 diabetes, raising concern over poor adherence.

Use of biologic or targeted-synthetic disease-modifying anti-rheumatic drugs and risk of diabetes treatment intensification in patients with rheumatoid arthritis and diabetes mellitus.

ObjectivesGiven that RA treatment might affect the severity of diabetes mellitus (DM), we compared the risk of DM treatment intensification in patients with both RA and DM newly initiating a biologic DMARD or tofacitinib.MethodsUsing claims data from the IBM MarketScan database (2005–2016), we identified patients aged ≥18 years with RA who initiated abatacept, a TNF inhibitor (TNFi), rituximab, tocilizumab or tofacitinib. Patients were required to have type 1 or type 2 DM and to use at least one antidiabetic drug at baseline. We assessed DM treatment intensification (i.e. addition of a new insulin or non-insulin antidiabetic medication). We also assessed non-insulin antidiabetic medication switching events.ResultsWe included 10 019 patients with RA and DM initiating a biologic DMARD or tofacitinib. Baseline insulin use was the highest in rituximab initiators (44%) and lowest in tofacitinib initiators (35%). The incidence rate per 1000 person-years for DM treatment intensification ranged from 148.2 (tofacitinib) to 198.0 (rituximab). The risk of DM treatment intensification was similar between abatacept and TNFi [hazard ratio (HR) 0.97, 95% CI: 0.82, 1.15], rituximab (HR 0.99, 95% CI: 0.79, 1.23) and tocilizumab (HR 0.94, 95% CI: 0.74, 1.19), but lower for tofacitinib compared with abatacept (HR 0.67, 95% CI: 0.50, 0.90). The risk of non-insulin DM treatment switching was not different between abatacept and other biologic DMARDs.ConclusionIn patients with both RA and DM, we found no difference in the risk of DM treatment switching or intensification after initiating abatacept vs TNFi, rituximab and tocilizumab, whereas the risk appeared to be lower for tofacitinib.

Factors Affecting Non-Insulin Antidiabetic Drug Adherence in Patients with Type 2 Diabetes: A Systematic Review

Objective To identify factors associated with medication non-adherence in patients with type 2 diabetes using non-insulin anti-diabetic medication.

A population-based analysis of antidiabetic medications in four Canadian provinces: Secular trends and prescribing patterns.

To use the Canadian Network for Observational Drug Effect Studies (CNODES) to describe drug utilization of antidiabetic medications in four Canadian provinces. With the use of data from CNODES, we constructed cohorts of patients with type 2 diabetes in four Canadian provinces (Manitoba, Ontario, Quebec, and Saskatchewan) who received their first-ever prescription for a noninsulin antidiabetic medication during the study period, defined as the earliest date of data availability in each province (range: 1993-1998) to the latest date of the data extraction in each province (range: 2013-2014). Prescriptions rates were calculated for all prescriptions by class and described over time. Across provinces, we identified 650 830 patients who initiated antidiabetic medications during the study period. In most provinces, the overall prescription rate of antidiabetic medications increased during the last two decades. Metformin particularly increased in popularity, surpassing sulfonylureas in all provinces as the most widely prescribed antidiabetic medication by the early 2000s. Thiazolidinediones grew in popularity from the onset of their availability until 2006 to 2007, at which point they rapidly declined. Dipeptidyl peptidase-4 inhibitors saw substantial growth in several provinces following their addition to provincial formularies in 2008 to 2012, while glucagon-like peptide-1 agonists experienced modest growth. Insulin prescription rates remained constant or steadily increased over the last two decades. CNODES can be used for cross-jurisdictional drug utilization studies. In Canada, trends in antidiabetic medication prescriptions followed changing guidelines reflecting up-to-date knowledge of drug effectiveness and safety.

National ambulatory care non-insulin antidiabetic medication prescribing trends in the United States from 2009 to 2015.

ObjectiveDespite their efficacy in lowering hemoglobin A1c, recent data suggest that sulfonylureas are associated with cardiovascular risk and hypoglycemia. The objective of this study was to determine whether prescribers decreased sulfonylurea use in favor of newer medications in the United States over seven years.Research design and methodsThis cross-sectional study utilized data from the Centers for Disease Control and Prevention’s National Ambulatory Medical Care Survey. Patient visits between 2009 and 2015 were included for patients who were at least 18 years old, had a documented prescription for a non-insulin antidiabetic medication, and a diagnosis of type 2 diabetes. Sample survey data were extrapolated to national estimates using data weights. Prescribing rates were calculated as the number of visits with a documented medication class divided by the total number of visits with a prescription for any diabetes medication class, times 100%.ResultsA total of 303 million patient visits were included in this study. The median (IQR) patient age was 64 (55–73) years old and 49.8% were male. Sulfonylurea prescribing rates decreased from 43% in 2009 to 36.5% in 2015. Prescribing of GLP-1 receptor agonists increased from 2009 to 2014 (3.95% to 5.30%), but then decreased to 4.19% in 2015. SGLT-2 inhibitor prescribing began in 2013 and increased to 7.3% by 2015. Metformin prescribing remained relatively stable over the study period (range 70% to 72%).ConclusionsNational ambulatory sulfonylurea prescribing decreased from 2009 to 2015 with a corresponding increase in newer non-insulin antidiabetic agent prescribing.

Mechanisms of cardiovascular protection of non-insulin antidiabetic medications

Patients with type 2 diabetes mellitus die most frequently from cardiovascular disease (CVD). Metabolic control is a cornerstone of both primary and secondary prevention of CVD: its important is two-fold since the normalization of HbA1c not only counteracts the onset, and the progression of microvascular complication, but has also important and positive role in reducing the risk of major adverse cardiovascular events (MACE). However, among the available glucose-lowering medications, some exert a direct CV protection independently from their ability to normalize metabolic control. In this review I will highlight the pathophysiological mechanisms underlying the claimed cardiovascular protection of the different glucose-lowering drugs, the available evidence-based data for their protection, the potential adverse effects, and the different phenotypes of patients eligible for a specific treatment. The knowledge of pathophysiological mechanisms for CV protection of each glucose-lowering medication, and the constraints of their use supports the health care professionals to individualize the normalization of metabolic control in patients with type 2 diabetes mellitus.

Impact of Appointment-Based Medication Synchronization on Proportion of Days Covered for Chronic Medications

Appointment-based medication synchronization (ABMS) programs have been associated with increased adherence and persistence to chronic medications. Adherence to statin therapy, angiotensin-converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), and non-insulin antidiabetic medications (NIDM) are used to determine a health plan’s Centers for Medicare and Medicaid Services (CMS) Star Rating under a pay-for-performance model. The objective of this study was to evaluate the impact of implementing an ABMS program on overall pharmacy adherence measures for statins, ACEI/ARBs, and NIDM, as presented through the Electronic Quality Improvement Platform for Plans and Pharmacies (EQuIPP©) platform. This retrospective, pre-post ABMS program study evaluated EQuIPP© generated adherence performance measures, represented as proportion of days covered (PDC), 6-months before and 6- and 12-months after the ABMS service for statin therapy, ACEIs/ARBs, and NIDM. All adherence measures showed statistically significant improvement in PDC percentage post ABMS implementation, except for NIDM percentage in 6-months post-ABMS service. This study shows that a comprehensive medication synchronization program can enhance adherence measures that are important to health plans to increase CMS Star Rating under a pay-for-performance model.

Real world management of pregestational diabetes not achieving glycemic control for many patients in the UK.

Our goal was to describe the management of pregestational diabetes in pregnant women in the United Kingdom. We used electronic medical records from The Health Improvement Network database between January 1995 and June 2012 to identify the first pregnancy in women 15 to 45years of age with pregestational diabetes type 1 or type 2. Information on lifestyle factors, demographic characteristics, prescription of specific antidiabetic medications, and glycemic control measures (HbA1c) was obtained from primary care provider records. We evaluated treatment patterns and HbA1c levels within 90days before the last menstrual period (prepregnancy period) and within each trimester of pregnancy. In a cohort of 1511 pregnant women with pregestational diabetes, 60% had type 1 and 40% type 2 diabetes. Among women with type 1 diabetes, 90% received antidiabetic medication (primarily insulin) prepregnancy and 92% during the first trimester. Among women with type 2 diabetes, 54% received antidiabetic medication (primarily metformin) during the prepregnancy period and 60% during the first trimester. Among women with nontreated diabetes type 2 before pregnancy, 22% initiated treatment by the first trimester (primarily insulin); those on noninsulin antidiabetic medications often switched to insulin. The proportion of women with at least 1 HbA1c value recorded within the prepregnancy period was 33% for type 1 (n=299) and 31% for type 2 diabetes (n=189); the corresponding proportions within the first trimester were 48% and 40%, respectively. Among women with recorded HbA1c, the prevalence of HbA1c>7% prepregnancy was 70% for type 1 and 52% for type 2 diabetes; the proportions within the first trimester were 73% and 46%, respectively. Management of pregnant women with diabetes seems to follow recommendations for pharmacological treatment. However, there is substantial room for improvement in HbA1c control, that is, in the planning of pregnancy in women with diabetes, in the initiation of antidiabetic medication among women with diabetes type 2 who may need it, and likely in the compliance with treatments in women with type 2 and type 1 diabetes.

Positive Impact of Continuous-Flow Left Ventricular Assist Device Implantation on Glycemic Control in Patients with Type 2 Diabetes Mellitus and Advanced Chronic Systolic Heart Failure.

To evaluate the impact of continuous-flow left ventricular assist device (LVAD) implantation on glycemic control in patients with type 2 diabetes mellitus and advanced chronic systolic heart failure. Retrospective medical record review. Large academic tertiary and quaternary care hospital. Eighty-three adults with type 2 diabetes mellitus and advanced chronic systolic heart failure who underwent implantation of a continuous-flow LVAD between July 1, 2008, and June 30, 2013. Baseline demographic data and laboratory values pertinent to glycemic control (hemoglobin A1c [A1C], total daily insulin requirements, noninsulin antidiabetic medication use, and body mass index [BMI]) were collected for each patient. Pre-LVAD data were compared with data obtained during the 24 months after LVAD implantation. The mean age of the study population was 61.3 years, 70% were men, and 63% had ischemic cardiomyopathy. The first available mean ± SD A1C after LVAD implantation was 6.21 ± 1.5% at a median of 4.8 months (interquartile range 3.3-8.9), which represented a significant decrease from the pre-LVAD A1C of 7.46 ± 1.5% (p<0.001). Average daily insulin requirements decreased by 22.9 units at the end of 24 months (p<0.001). Over half of patients with prescriptions for noninsulin antidiabetic medications were able to discontinue therapy by the end of the study. Of note, BMI increased in the second year after LVAD implantation from a baseline of 32.3 kg/m2 to 34.9 kg/m2 (p=0.004). Regression analysis revealed that baseline A1C was the only independent predictor of change in A1C. LVAD implantation was associated with a significant improvement in glycemic control. Further prospective studies are needed to evaluate the long-term impact of LVAD implantation on the clinical course of diabetes.