bluuebunny/crossref_metadata_2025_split huggingface dataset:
Software Price Modeling of Semaglutide
Authors: EILERMAN BRADLEY , TESTA LEONARD J. 
Published: June 2018

GlucosePATH is a clinically validated decision support system which creates drug regimens for patients with type 2 diabetes. Regimens are optimized for HbA1c, weight, side effect and benefit impact, adherence and cost using a composite score from 0 to 100. Used on a population level, GlucosePATH can model drug distribution for sets of clinical values, showing drug prescription frequency to that population. As new agents such as semaglutide become available, projected distribution of these options can be described at various prices. Among other things, this shows the maximum and optimal price for a new agent, given the cost and performance of existing agents.
A data set of 191 patients with HbA1c &gt;7 was drawn from a distribution of patients cared for by PCPs in a large health system. Total monthly cost of care was computed based on the mean retail cost drawn from the GoodRX API. Using scores drawn from GlucosePATH, drugs were redistributed to find the lowest total cost at which the population’s score was &gt;70 out of 100. Total retail cost of care averaged $475.03 per month per patient for the 191 patients. Redistributed medication at this price generated a mean composite score of 71.5 at a projected mean HbA1c of 6.9.
Two price points were established for semaglutide. The “maximal price” (MP) is the highest price at which use of the agent in the population does not exceed the control group’s retail cost of care and the composite score threshold is met. (That is, introducing the new agent does not increase cost or worsen results for the population.) The “maximal revenue” (MR) is the price at which the agent’s manufacturer maximizes their gross revenue for the agent in the population.
Price optimization for semaglutide showed a MP between $800 and $825 (retail price: $808). At its MP, semaglutide would be prescribed to approximately 17% of the population with mean composite score of 76.1 and mean HbA1c of 6.9. At semaglutide’s MR of $450 per month, it would be prescribed to approximately 49% of the population and generate a mean composite score of 77.8 with a mean HbA1c of 6.9.

Disclosure
B. Eilerman: Speaker's Bureau; Self; AbbVie Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Sanofi, Novo Nordisk Inc., Orexigen Therapeutics, Inc., Corcept Therapeutics, Eli Lilly and Company, Merck & Co., Inc., Janssen Pharmaceuticals, Inc.. Other Relationship; Self; PATH Decision Support Software LLC. L.J. Testa: Stock/Shareholder; Self; PATH Decision Support Software LLC.
Insulin Secretory Response Is Enhanced in Early Pregnancy
Authors: POWE CAMILLE E. , TANGREN JESSICA S. , LEONG AARON , PERCY SHANANSSA , KRINSKY SCOTT , ARENAS JULIANA , CAYFORD MELODY , FLOREZ JOSE C. , HIVERT MARIE-FRANCE , THADHANI RAVI 
Published: June 2018

Background: Emerging evidence links early pregnancy (EP) abnormalities in glucose tolerance to adverse outcomes, but glycemic physiology changes in EP are not well characterized. We hypothesized that EP insulin secretory response would be enhanced compared to postpartum (PP), independent of insulin sensitivity.
Methods: To date, 14 women without pre-existing diabetes have undergone 75-gram oral glucose tests with timed measurements of insulin and glucose at 10-15 weeks gestation (EP) and 5-15 weeks after delivery (PP). We tested for a difference in insulin secretory response (Stumvoll 1st phase estimate) in EP compared to PP with adjustment for insulin sensitivity (Matsuda index) using a linear mixed effects model. We explored associations between participant characteristics and the change in insulin secretion between EP and PP using simple linear regression.
Results: Participants had a mean (standard deviation) age of 32.3 (5.0) years and BMI of 27 (4.9) kg/m2; 43% were nulliparous and 43% were racial/ethnic minorities. In EP vs. PP, insulin secretory response (Stumvoll 1st phase estimate) was 1474 (706) vs. 1221 (398) pmol/L, while insulin sensitivity (Matsuda index) was 9.4 (7.2) vs. 9.7 (6.8). Insulin secretory response was significantly enhanced in EP as compared to PP before and after adjustment for insulin sensitivity (β=236, standard error=115, P=0.04 in adjusted model). Lower insulin sensitivity in EP was associated with a greater change in insulin secretory response between EP and PP (β=-42.2, standard error=14.0, P=0.01). There was no association between age, BMI in EP, or the change in BMI between EP and PP and the change in insulin secretory response.
Conclusion: We found evidence of enhancement of insulin secretory response early in pregnancy, in the absence of a change in insulin sensitivity. In light of evidence that identification and treatment of mild glucose intolerance early in pregnancy may be beneficial, larger studies of glycemic physiology in the 1st trimester are warranted.

Disclosure
C.E. Powe: None. J.S. Tangren: None. A. Leong: None. S. Percy: None. S. Krinsky: None. J. Arenas: None. M. Cayford: None. J.C. Florez: Consultant; Self; Intarcia Therapeutics, Inc.. Consultant; Spouse/Partner; Santen. M. Hivert: None. R. Thadhani: None.
Failure of Maternal Glucose-Insulin Adjustments in Pregnancy Might Contribute to Poor Fetal Growth in India
Authors: DESHMUKH MADHURA KISHOR , DAMLE HEMANT , BHAT DATTATRAY , MEMANE NILAM S. , RAUT DEEPA A. , BHALERAO ABOLI A. , BONDARDE SOMNATH J. , YAJNIK CHITTARANJAN S. 
Published: June 2018

Background: In the well-nourished Western populations maternal insulin concentrations (and insulin resistance) progressively increase during gestation to support fetal growth. Information in undernourished women from LMICs is scarce. We investigated serial glucose-insulin and lipid concentrations from early to late pregnancy in rural and urban Indian women, and studied their association with offspring birth weight.
Methods: Women from antenatal clinics were enrolled in early pregnancy. Fasting glucose, insulin, cholesterol and triglyceride concentrations were measured at 16, 28 and 33 weeks gestation and a75gm OGTT was performed at 28 weeks gestation. GDM was diagnosed using the prevalent WHO 1999/ IADPSG 2011 criteria. Demographic and anthropometric measurements were obtained, and babies were measured at birth.
Results: A total of 256 (161 rural, 95 urban) women were enrolled: they were 23 y old, 153 cm tall, and had a BMI 20.7 kg/m2at ∼16 weeks gestation. Thirty nine GDM women (22 rural) were excluded from further analysis. In 217 normal glucose tolerant women, fasting plasma glucose progressively fell with increasing gestation, insulin concentrations and HOMA-IR remained similar (51% showed a fall); total and HDL cholesterol and triglyceride concentrations increased. Urban women were older, taller and heavier, and had significantly higher glucose, insulin and HOMA-IR compared to rural women; they gained 7kg and rural women 6kg between early and late visits. Mean birth weight was 2.8kg, 39% babies were SGA and 1% LGA (INTERGROWTH). Birth weight was positively associated with maternal size (height, weight, BMI) and fasting plasma glucose concentrations. HOMA-IR was not independently associated.
Conclusion: The short and undernourished women from India failed to increase their insulin resistance with increasing gestation. This may be a novel explanation for fetal growth restriction in India and for its short term and long term sequele, including risk of diabetes.

Disclosure
M. Deshmukh: None. H. Damle: None. D. Bhat: None. N.S. Memane: None. D.A. Raut: None. A.A. Bhalerao: None. S.J. Bondarde: None. C.S. Yajnik: None.
Association between Glyburide Dose and Adverse Neonatal Outcomes in Women with Gestational Diabetes
Authors: FEGHALI MAISA N. , CARITIS STEVE , CATOV JANET M. , SCIFRES CHRISTINA M. 
Published: June 2018

Glyburide is used to treat women with gestational diabetes (GDM). However, recent data has demonstrated that it crosses the placenta, and concerns about the neonatal effects of glyburide treatment including fetal overgrowth and neonatal hypoglycemia persist.
We sought to assess if there are subsets of women treated with glyburide who are at increased risk for adverse neonatal outcomes compared to women treated with medical nutritional therapy (MNT) alone using a retrospective cohort of 1,012 women with GDM. We collected characteristics including glucose values and pregnancy outcomes. We used bivariate and multivariable logistic regression analyses to assess the association between GDM treatment and pregnancy outcomes.
Treatment was divided into categories of MNT (n=343), glyburide &lt;7.5 mg (n=495), and glyburide ≥7.5 mg/day (n=173). When compared to women treated with MNT or glyburide &lt;7.5 mg, those treated with glyburide ≥7.5 mg/day were more likely to be obese (28.5 vs. 48.3 vs. 63.2%, p&lt;0.001), gain excessive weight (35.2 vs. 42.9 vs. 56.4%, p&lt;0.0001), and had higher mean glucose (106.4 vs. 114.3 vs. 121.9, p&lt;0.001). Higher glyburide doses were associated with an increased risk for large for gestational age (LGA) and neonatal hypoglycemia. After adjusting for covariates including nulliparity, prepregnancy BMI, gestational weight gain, prematurity, and maternal glucose, women treated with ≥7.5 mg/day were 2.6-fold more likely to deliver an LGA infant, but there was no increased risk for hypoglycemia.
Our findings suggest that neonatal outcomes in women on lower glyburide doses are similar to those treated with MNT, but higher doses are associated with fetal overgrowth. Further studies are needed to determine optimal management of women receiving glyburide, specifically the maximal dose for use in pregnancy and identification of women who respond well to lower doses.

Disclosure
M.N. Feghali: None. S. Caritis: None. J.M. Catov: None. C.M. Scifres: None.
Effect of Preconceptional Care on Maternal and Fetal Outcomes in Type 1 Diabetes
Authors: DALAMA BELEN , DE URBINA ANA ORTIZ , GOYA MARIA , ARÉVALO SILVIA , RODÓ CARLOTA , MESA JORDI 
Published: June 2018

Introduction: Pregnancy in women with type 1 diabetes (T1D) is associated with increased risk of maternal complications and neonatal morbidity. Our aim is to describe and compare maternal metabolic control and maternal-fetal outcomes (MFO) among pregnant T1D patients optimized preconceptionally (OP) as compared to those with unplanned pregnancies (UP).
Design and methods: We carried out a retrospective study of 92 singleton pregnancies in 79 T1D Caucasian patients, 59 of them were OP and 33 UP who attended our Diabetes and Pregnancy Unit since 2013 to 2017. In each of the groups were evaluated the pre-pregnancy characteristics, in each trimester and the MFO. Preconception A1C goal was &lt;6% without exceeding 6.5% with a glycemic target of a fasting glucose between 70-95mg/dl and 1 hour postprandial 90 -140 mg/dl.
Results: Both groups did not differ by age: 34 (36-43) vs. 31 (21-42) years, T1D duration: 17 (2-35) vs. 14 (1-31) years and pregestational BMI. Pre-pregnancy A1C in OP vs. UP was 5.9% (5.1-6.0) vs. 7.4% (6.8-10.1) p&lt; 0.001. During the first trimester: 5.7% (5.2-6.5) vs. 6.6% (5.7-7.8) p&lt; 0.01, in the 2th: 5.8% (4.8-6.4) vs. 6.3% (5.3-7.0) and in the 3th: 5.9% (5.0-6.5) vs. 6.2% (5.2-6.9) without differences in weight gain and preeclampsia development. OP vs. UP patients had a 27.1% of cesarean delivery vs. 33.3% (p&lt;0.05) with no differences in preterm and instrumental delivery. Regarding fetal outcomes the neonatal birth weight was 3270 gr (2198-4280) vs. 3370 gr (1200-4870) with a higher percentage in the UP of larger for gestational age newborns (15.2% vs. 3.3% p&lt;0.05), malformations (1.6% vs. 15.1% p&lt;0.05) and hypoglycemia (6.7% vs. 27.2% p&lt;0.05). No differences in macrosomía, small for gestational age, shoulder dystocia, jaundice or respiratory distress.
Conclusion: In women with preexisting T1D preconceptional counseling and glycemic optimization represent a fundamental step towards improved pregnancy outcomes. Pre-pregnancy A1C &lt;6% and during the 1th trimester seems to decrease the risk of adverse outcomes.

Disclosure
B. Dalama: None. A. Ortiz de Urbina: None. M. Goya: None. S. Arévalo: None. C. Rodó: None. J. Mesa: None.
Should We Perform an OGTT in All Latino Pregnant Women? The Negative Predictive Value of a Fasting Blood Glucose
Authors: MANCILLAS-ADAME LEONARDO G. , GONZALEZ CAMILO D. , VILLARREAL JOSE A. , SALDIVAR-RODRIGUEZ DONATO , LAVALLE-GONZALEZ FERNANDO J. , RODRIGUEZ-GUTIERREZ RENE , GONZALEZ-GONZALEZ JOSE G. 
Published: June 2018

Background: Latino women are considered a high-risk group, prone to develop GDM. Currently, according to the ADA Standard of Care Recommendations, these subjects should undergo screening with an OGTT, which is a time and resource consuming procedure. A better selection of the individual would favor a cost-effective diagnostic approach. Our hypothesis is that we could find a fasting blood glucose threshold able to predict a normal OGTT response.
Methods: We analyzed the results of 363 one-step, 75-g OGTT performed in our clinic during 2017. Patients with a previously known glucose tolerance abnormality were excluded from the study.
Results: The fasting glucose value was diagnostic of GDM in 83/363 cases. After selecting only those cases with fasting value lower than 92 mg/dL, 22 additional subjects were diagnosed with GDM. The one-hour post-load value criteria was met in 16/280 (5.71%) whilst the 2 hour value diagnosed 6 additional subjects (2.86%). Two patients had both one and two hour positive criteria. The area under the curve was 0.75, for fasting blood glucose as a predictor of an abnormal glucose response.
Conclusions: In our population from a Mexican University Hospital, the fasting blood glucose detected fourfold the cases of GDM vs. the OGTT. It might be cost effective to perform a fasting glucose prior to prescribe an OGTT in pregnant subjects.

Disclosure
L.G. Mancillas-Adame: None. C.D. Gonzalez: None. J.A. Villarreal: None. D. Saldivar-Rodriguez: None. F.J. Lavalle-Gonzalez: None. R. Rodriguez-Gutierrez: None. J.G. Gonzalez-Gonzalez: None.
Maternal Diabetes during Pregnancy and Early Childhood Obesity—A Population-Level Analysis
Authors: BOWKER SAMANTHA L. , SAVU ANAMARIA , YEUNG ROSEANNE O. , RYAN EDMOND A. , KAUL PADMA 
Published: June 2018

We examined the association between maternal diabetes status (preexisting diabetes mellitus (pre-DM), gestational diabetes mellitus (GDM), and no DM) during pregnancy and overweight or obesity status of the offspring in early childhood (4-6 years). Immunization records, containing height and weight at the time of preschool vaccination for children born between Jan 2005-Aug 2013 in Alberta, Canada were linked with the following: 1) maternal hospitalization and outpatient records prior to delivery; and 2) registry data containing birth weight, parity, and gestational age. World Health Organization (WHO) criteria were used to categorize children as overweight or obese. Our cohort had 91,382 live births from 68,457 mothers. Rates of pre-DM, GDM and no-DM were 0.8%, 6.2%, and 93.0%, respectively (Table). Childhood overweight/obesity rates were significantly higher among women with pre-DM or GDM, than with no-DM. After adjustment, both GDM and pre-DM were associated with a higher likelihood of having an overweight/obese child. Breast feeding data were available for 63,374 children. A higher proportion of GDM and pre-DM babies were not breast fed, which was also associated with a higher risk of childhood obesity. The impact of maternal diabetes on offspring weight continues beyond birth to early childhood. This association may be further exacerbated by breast feeding challenges in women with diabetes.

Disclosure
S.L. Bowker: None. A. Savu: None. R.O. Yeung: Consultant; Self; Sanofi. Research Support; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. E.A. Ryan: None. P. Kaul: None.
History of Falls in the Previous Year Predicts Frailty among Community-Dwelling Older Patients with Diabetes Mellitus
Authors: VALENCIA WILLY MARCOS , MOGHADAM NIMA , BALDA-CANIZARES JAVIER , MINTZER MICHAEL J. , DANG STUTI , RUIZ JORGE G. 
Published: June 2018

Frailty is a state of vulnerability to stressors resulting in higher morbidity, mortality and healthcare utilization in older adults. Diabetes mellitus is considered a risk factor for both frailty and falls in older adults. The aim of this study was to determine in a community cohort of older patients (65 years and older) with type 2 diabetes mellitus (T2DM) whether a history of falls is associated with frailty. Community dwelling older Veterans with T2DM underwent frailty assessment with the validated 5-item FRAIL Scale (frail ≥ 3; pre-frail 1-2; robust 0 points) between January 2016 and December 2017. We aggregated data on patients with a least one fall in the previous year. Binomial logistic regression was used to examine the association between a history of falls in the previous year and frailty. Among 868 patients (mean age 74 ± 7 years, 98% men), 31% were robust, 36% prefrail, and 33% frail. Over the previous year, 164 falls occurred among 1older patients. The number of older individuals with at least one fall in the previous year was significantly higher in the frail as compared with prefrail and robust groups: 20%, 9%, and 9% respectively (p&lt;.0005). A history of falls in the previous year was associated with an increased risk for frailty (odds ratio: 2.54 95% CI: 1.60-4.03). The population-attributable risk associated with a history of falls was 44% for frailty.
In conclusion, a history of falls in the previous year is a strong predictor of frailty in older patients with T2DM. Falls should be a key component of the clinical evaluation of older patients with T2DM.

Disclosure
W. Valencia: None. N. Moghadam: None. J. Balda-Canizares: None. M.J. Mintzer: None. S. Dang: None. J.G. Ruiz: None.
Cost-Related Barriers to New Diabetes Medications—A National Physician Survey
Authors: HAM SANDRA A. , NATHAN AVIVA , LAITEERAPONG NEDA , SARGIS ROBERT M. , QUINN MICHAEL T. , HUANG ELBERT 
Published: June 2018

Background: In recent clinical trials, some SGLT2is and GLP-1 receptor agonists have been shown to reduce cardiovascular events, leading to their prioritization for patients with cardiovascular disease in diabetes care guidelines. However, because these medications are costly, oftentimes medication access is limited by insurance companies.
Objectives: To determine the frequency that physicians encounter cost-related barriers to prescribing new diabetes medications.
Methods: We mailed a survey to a national sample of 720 primary care physicians (PCPs) and 480 endocrinologists in 2016 (adjusted response rate, 41%). Physicians were asked how often their patients were unable to start a new diabetes medication in general, and, specifically, an SGLT2i, because it was too expensive. Physicians also reported the frequency of completing a prior authorization (PA) for a new diabetes medication.
Results: In 2016, 28% (N=101) and 37% (N=129) of physicians reported that their patients were unable to start medications in general, and specifically, SGLT2is, due to costs “most of the time”/“always.” More PCPs (45%, N=86) than endocrinologists (26%, N=43) were unable to start SGLT2is due to costs. Daily PA were reported by 43% of physicians (N=151); 62% (N=101) endocrinologists completed PAs daily. Adjusting for specialty and panel size, physicians with &gt;50% of patients age &gt;65 were more likely to report that patients were unable to start a new medication or SGLT2i due to costs (OR=2.25, 95% CI=1.38-3.67; p=0.001 and OR=1.63, CI=1.02-2.60, p=0.04). Endocrinologists (OR=5.03, CI=3.09-8.18; p&lt;0.001) and physicians with &gt;1000 patients in their panel (OR=2.69, CI=1.61-4.49; p&lt;0.001) were more likely to complete PAs daily.
Conclusions: U.S. physicians experience significant cost-related barriers to prescribing new diabetes medication classes. Pharmacy benefit management strategies will need to be updated to facilitate access to glucose-lowering medications with clear cardiovascular benefit.

Disclosure
S.A. Ham: None. A. Nathan: None. N. Laiteerapong: None. R.M. Sargis: Advisory Panel; Self; CVS/Caremark. M.T. Quinn: None. E. Huang: None.
Understanding the Relationship between Primary Care Provider (PCP) Encounter Cadence, Medication Adherence, and Diabetes Control
Authors: WIXSON SARAH E. , DOBBINS JESSICA , CORDIER TRISTAN A. , HAUGH GIL , RENDA ANDREW , HAPPE LAURA E. , TURCHIN ALEXANDER 
Published: June 2018

Introduction: Regular PCP encounters are associated with wellbeing; there is limited evidence to support the ideal PCP encounter cadence to optimize patient outcomes. The aim of this study was to measure the association between PCP encounter cadence and medication adherence and diabetes control, among those newly diagnosed with T2DM.
Methods: A cohort of 7,106 persons enrolled in a Medicare Advantage health plan and newly diagnosed with T2DM between 7/1/12-6/30/13, was identified and followed for 36 months. Two methods measured PCP encounter cadence: total PCP encounters (frequency) and quarters with PCP encounter (regularity). Proportion of days covered (PDC) assessed noninsulin diabetes medication (NIDM) adherence (PDC ≥80.0%). Diabetes control was defined as A1c ≤ 8.0%. Logistic regression was used to measure the relationship between PCP encounter cadence and outcomes (NIDM adherence, diabetes control). Covariates included patient demographics, Charlson Comorbidity Index score, chronic conditions, healthcare utilization, insulin use, and prior NIDM adherence and diabetes control.
Results: Overall, 5,212 and 326 people met inclusion criteria for the NIDM adherence and diabetes control analyses, respectively. Adjusted models indicated that each additional PCP encounter was associated with a 12.3% increase in the likelihood of NIDM adherence (95% CI 1.10, 1.15), and each additional quarter with a PCP encounter was associated with a 27.4% increase in the likelihood of NIDM adherence (95% CI 1.22, 1.33). PCP encounters (OR 1.06; 95% CI 1.00, 1.12) and quarters with a PCP encounter (OR 1.13; 95% CI 0.98, 1.30) were directionally associated with diabetes control.
Conclusion: Our findings suggest that frequency and regularity of PCP encounters were associated with medication adherence. This study contributes to the data needed to establish evidence-based guidelines for PCP encounter cadence, for those newly diagnosed with T2DM.

Disclosure
S.E. Wixson: None. J. Dobbins: Employee; Self; Humana Inc. T.A. Cordier: Employee; Self; Humana Inc.. Stock/Shareholder; Self; Humana Inc.. G. Haugh: None. A. Renda: None. L.E. Happe: Employee; Self; Humana. Other Relationship; Self; Journal of Managed Care Pharmacy. A. Turchin: Research Support; Self; Sanofi-Aventis. Advisory Panel; Self; Merck Sharp & Dohme Corp., Monarch Medical Technologies. Stock/Shareholder; Self; Brio Systems. Research Support; Self; Eli Lilly and Company.