First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial.

BACKGROUND: Cemiplimab provided significant survival benefit to patients with advanced non-small-cell lung cancer with PD-L1 tumour expression of at least 50% and no actionable biomarkers at 1-year follow-up. In this exploratory analysis, we provide outcomes after 35 months' follow-up and the effect of adding chemotherapy to cemiplimab at the time of disease progression. METHODS: EMPOWER-Lung 1 was a multicentre, open-label, randomised, phase 3 trial. We enrolled patients (aged ≥18 years) with histologically confirmed squamous or non-squamous advanced non-small-cell lung cancer with PD-L1 tumour expression of 50% or more. We randomly assigned (1:1) patients to intravenous cemiplimab 350 mg every 3 weeks for up to 108 weeks, or until disease progression, or investigator's choice of chemotherapy. Central randomisation scheme generated by an interactive web response system governed the randomisation process that was stratified by histology and geographical region. Primary endpoints were overall survival and progression free survival, as assessed by a blinded independent central review (BICR) per Response Evaluation Criteria in Solid Tumours version 1.1. Patients with disease progression on cemiplimab could continue cemiplimab with the addition of up to four cycles of chemotherapy. We assessed response in these patients by BICR against a new baseline, defined as the last scan before chemotherapy initiation. The primary endpoints were assessed in all randomly assigned participants (ie, intention-to-treat population) and in those with a PD-L1 expression of at least 50%. We assessed adverse events in all patients who received at least one dose of their assigned treatment. This trial is registered with ClinicalTrials.gov, NCT03088540. FINDINGS: Between May 29, 2017, and March 4, 2020, we recruited 712 patients (607 [85%] were male and 105 [15%] were female). We randomly assigned 357 (50%) to cemiplimab and 355 (50%) to chemotherapy. 284 (50%) patients assigned to cemiplimab and 281 (50%) assigned to chemotherapy had verified PD-L1 expression of at least 50%. At 35 months' follow-up, among those with a verified PD-L1 expression of at least 50% median overall survival in the cemiplimab group was 26·1 months (95% CI 22·1-31·8; 149 [52%] of 284 died) versus 13·3 months (10·5-16·2; 188 [67%] of 281 died) in the chemotherapy group (hazard ratio [HR] 0·57, 95% CI 0·46-0·71; p<0·0001), median progression-free survival was 8·1 months (95% CI 6·2-8·8; 214 events occurred) in the cemiplimab group versus 5·3 months (4·3-6·1; 236 events occurred) in the chemotherapy group (HR 0·51, 95% CI 0·42-0·62; p<0·0001). Continued cemiplimab plus chemotherapy as second-line therapy (n=64) resulted in a median progression-free survival of 6·6 months (6·1-9·3) and overall survival of 15·1 months (11·3-18·7). The most common grade 3-4 treatment-emergent adverse events were anaemia (15 [4%] of 356 patients in the cemiplimab group vs 60 [17%] of 343 in the control group), neutropenia (three [1%] vs 35 [10%]), and pneumonia (18 [5%] vs 13 [4%]). Treatment-related deaths occurred in ten (3%) of 356 patients treated with cemiplimab (due to autoimmune myocarditis, cardiac failure, cardio-respiratory arrest, cardiopulmonary failure, septic shock, tumour hyperprogression, nephritis, respiratory failure, [n=1 each] and general disorders or unknown [n=2]) and in seven (2%) of 343 patients treated with chemotherapy (due to pneumonia and pulmonary embolism [n=2 each], and cardiac arrest, lung abscess, and myocardial infarction [n=1 each]). The safety profile of cemiplimab at 35 months, and of continued cemiplimab plus chemotherapy, was generally consistent with that previously observed for these treatments, with no new safety signals INTERPRETATION: At 35 months' follow-up, the survival benefit of cemiplimab for patients with advanced non-small-cell lung cancer was at least as pronounced as at 1 year, affirming its use as first-line monotherapy for this population. Adding chemotherapy to cemiplimab at progression might provide a new second-line treatment for patients with advanced non-small-cell lung cancer. FUNDING: Regeneron Pharmaceuticals and Sanofi.

Use of Connected Pen as a Diagnostic Tool to Evaluate Missed Bolus Dosing Behavior in People with Type 1 and Type 2 Diabetes.

Objective: This study used connected pen to determine missed bolus dose (MBD) frequency during masked and unmasked continuous glucose monitoring (CGM) periods and examined its link with time-in-range (TIR), time-above-range (TAR), time-below-range (TBR), and key participant characteristics in people with diabetes. Methods: This was a 12-week, single-arm, exploratory, two-period study for people with type 1 diabetes (T1D) or type 2 diabetes (T2D). The primary objective was to estimate the average number of MBD during masked and real-time CGM use. The secondary objective was to estimate the average percent TIR and its relationship to MBD. An exploratory objective was to investigate the participant characteristics that were associated with MBD. Data were analyzed for differences in MBD by diabetes type and other participant characteristics, by CGM period, and by hypoglycemic fear scores. Results: Participants (n = 64; T1D, n = 38; T2D, n = 26) were 48 ± 11.9 years old and 44% were female. From the masked to the unmasked period, MBD, %TAR, %TBR, and glycated hemoglobin decreased significantly (0.74 MBD/day to 0.62 MBD/day, P = 0.008; 53.6%-48.1%, P = 0.004; 4.49%-2.93%, P < 0.001; mean 8.8%-8.4%, P < 0.001, respectively), while %TIR increased significantly (41.9%-49.0%, P < 0.001). MBD/day was negatively associated with TIR (P = 0.016) and positively associated with TAR (P = 0.015) for T1D and positively associated with TBR (P = 0.024) for T2D in the masked period only. MBD was significantly associated with fear of hypoglycemia for T2D, but not T1D. Conclusions: MBD is associated with reduced TIR when CGM is masked and tailored therapeutic approaches are needed for T1D and T2D populations.

Reasons for discontinuing insulin and factors associated with insulin discontinuation in patients with type 2 diabetes mellitus: a real-world evidence study.

BACKGROUND: Evidence suggests that insulin therapy of patients with type 2 diabetes mellitus (T2DM) is frequently discontinued. However, the reasons for discontinuing insulin and factors associated with insulin discontinuation in this patient population are not well understood. METHODS: We conducted a retrospective cohort study of adults with T2DM prescribed insulin between 2010 and 2017 at Partners HealthCare. Reasons for discontinuing insulin and factors associated with insulin discontinuation were studied using electronic medical records (EMR) data. Natural language processing (NLP) was applied to identify reasons from unstructured clinical notes. Factors associated with insulin discontinuation were extracted from structured EMR data and evaluated using multivariable logistic regression. RESULTS: Among 7009 study patients, 2957 (42.2%) discontinued insulin within 12 months after study entry. Most patients who discontinued insulin (2121 / 71.7%) had reasons for discontinuation documented. The most common reasons were improving blood glucose control (33.2%), achieved weight loss (18.5%) and initiation of non-insulin diabetes medications (16.7%). In multivariable analysis adjusted for demographics and comorbidities, patients were more likely to discontinue either basal or bolus insulin if they were on a basal-bolus regimen (OR 1.6, 95% CI 1.3 to 1.8; p <  0.001) or were being seen by an endocrinologist (OR 2.6; 95% CI 2.2 to 3.0; p <  0.001). CONCLUSIONS: In this large real-world evidence study conducted in an area with a high penetration of health insurance, insulin discontinuation countenanced by healthcare providers was common. In most cases it was linked to achievement of glycemic control, achieved weight loss and initiation of other diabetes medications. Factors associated with and stated reasons for insulin discontinuation were different from those previously described for non-adherence to insulin therapy, identifying it as a distinct clinical phenomenon.

Multicategory Outcome Weighted Margin-based Learning for Estimating Individualized Treatment Rules.

Due to heterogeneity for many chronic diseases, precise personalized medicine, also known as precision medicine, has drawn increasing attentions in the scientific community. One main goal of precision medicine is to develop the most effective tailored therapy for each individual patient. To that end, one needs to incorporate individual characteristics to detect a proper individual treatment rule (ITR), by which suitable decisions on treatment assignments can be made to optimize patients' clinical outcome. For binary treatment settings, outcome weighted learning (OWL) and several of its variations have been proposed recently to estimate the ITR by optimizing the conditional expected outcome given patients' information. However, for multiple treatment scenarios, it remains unclear how to use OWL effectively. It can be shown that some direct extensions of OWL for multiple treatments, such as one-versus-one and one-versus-rest methods, can yield suboptimal performance. In this paper, we propose a new learning method, named Multicategory Outcome weighted Margin-based Learning (MOML), for estimating ITR with multiple treatments. Our proposed method is very general and covers OWL as a special case. We show Fisher consistency for the estimated ITR, and establish convergence rate properties. Variable selection using the sparse l 1 penalty is also considered. Analysis of simulated examples and a type 2 diabetes mellitus observational study are used to demonstrate competitive performance of the proposed method.

Treatment Patterns, Adherence, and Persistence Associated With Human Regular U-500 Insulin: A Real-World Evidence Study.

OBJECTIVE | Human regular U-500 insulin (U-500R) is concentrated insulin with basal and prandial activity that can be used as insulin monotherapy. The goal of this study was to better understand treatment patterns (total daily dose [TDD] and concomitant medications), adherence, and persistence in real-world patients treated with U-500R. DESIGN AND METHODS | We selected patients from the Truven Health MarketScan database who initiated U-500R between 2010 and 2013. We collected data for three periods: pre-index (12 months before initiation), post-index (12 months after initiation or until a gap of ≥60 days in U-500R claims), and follow-up (12 months after post-index). Data were analyzed using descriptive statistics and a regression model as appropriate. RESULTS | We identified 1,582 patients who met the selection criteria. The median TDD of U-500R during the post-index period was 333 units/day, with 70.0% of patients using 300-400 units/day. During the post-index period, 74.1% of patients had U-500R claims that did not overlap with prescriptions for other insulins, interpreted as U-500R monotherapy. Among patients with ≥1 U-500R fill in the post-index period (n = 1,208), 54.4% had a medication possession ratio (MPR, a measure of adherence) ≥80%. Although 849 patients had a gap of ≥60 days in U-500R claims in the post-index period, 602 of those resumed U-500R in the follow-up period. Of the 733 patients who had no gap in U-500R claims in the post-index period, 286 had a gap of ≥60 days in claims in year 2, and 447 continued with U-500R treatment beyond 2 years. CONCLUSION | These results demonstrate that U-500R was commonly used as insulin monotherapy, with a median TDD >300 units/day. Compared with published, relevant studies of other insulins, U-500R showed similar or greater adherence and persistence rates. These new data may help guide clinical decision-making when choosing insulin therapy for patients requiring high doses of insulin.

Long-term effectiveness of the Diabetes Conversation Map™ Program on health outcomes: A case-control retrospective cohort study.

AIM: To evaluate the clinical and health behavioural outcomes of a large sample of participants from the Diabetes Conversation Map™ Program. DESIGN: A matched-case-control study that was performed on a retrospective cohort study. METHODS: Participants were 11,053 Clalit Health Services members with type 2 diabetes who enrolled in the Diabetes Conversation Map™ Program between January 2010 - April 2016. The matched-control group was formulated using sequential matching, by matching cases to controls at a ratio of 1:3, based on age, sex, and HbA1c level. The associations between the programme group and annual clinical and health behaviours were assessed between cases and controls at five time points using linear and Poisson regression analyses. RESULTS: The intervention group had significantly lower HbA1c, glucose, and low-density lipoprotein levels and more frequent glucose blood testing each year up to 36 month post-enrolment compared with the matched controls. Other outcomes were significantly different for shorter time periods, including higher high-density lipoprotein and lower triglyceride levels at 6- and 12-month follow-up and lower diastolic blood pressure and greater medication adherence at 6-month follow-up. CONCLUSIONS: Enrolment in the programme was associated with improved clinical and health behaviour outcomes for at least 6 months and most outcomes persisted for up to 36 months. IMPACT: This is the first study to evaluate the Diabetes Conversation Map™ Program with a large sample over long period of time. This nurse-led group intervention evaluation adds to the literature on health outcomes on the lives of patients with type 2 diabetes. STUDY REGISTRATION: This study was registered retrospectively to the Open Science Framework, the registration form can be found at: https://osf.io/63cse.

Treatment Patterns and Characteristics of Individuals Initiating High-Dose Insulin for Type 2 Diabetes Mellitus.

BACKGROUND: Few studies have examined patient characteristics and treatment patterns of high-dose insulin therapy (> 200 units/day) among patients with type 2 diabetes mellitus (T2DM). OBJECTIVE: To understand patient characteristics, dosing, adherence, and persistence related to high-dose insulin therapy. METHODS: This was a retrospective observational study that used administrative claims from a large national health plan. Patients were identified who had been diagnosed with T2DM and who were aged 18-89 years, enrolled in a commercial or Medicare Advantage Prescription Drug plan, newly initiated on a total daily dose (TDD) > 200 units of insulin between January 2011 and August 2015. Patients were required to be enrolled 6 months before and 12 months after the index date. Patients were categorized to Regimen-100 if treated with U-100 insulin only or Regimen-500 if treated with U-500R with or without U-100. Baseline demographic and clinical characteristics were evaluated. An adjustment factor for the days supply was calculated as the ratio of median time between insulin claims, and median pharmacy reported days supply for each insulin prescription. Adjusted days supply, quantity, and concentration were used to calculate TDD for each quarter after the index date. Adherence was measured as the proportion of days covered (PDC) for each regimen. Persistence was measured in 2 ways: the percentage of patients remaining on index medications in each quarter and the proportion of patients who maintained TDD > 200 units during all 4 quarters of the 12-month post-index period. RESULTS: We identified 2,339 patients newly titrated up to TDD > 200 units on either Regimen-100 (2,062, 88.2%) or Regimen-500 (277, 11.8%). Patients on Regimen-500 were slightly younger with higher prevalence of comorbidities. The mean TDD (SD) for Regimen-100 decreased from 228.6 (36.0) units during the first quarter to 194.2 (181.4) units during the last quarter. The mean TDD (SD) for Regimen-500 increased from 294.2 (102.2) units in the first quarter to 304.8 (281.6) units in last quarter. The average adherence to the high-dose insulin regimen was 68.2% (30.7; median 72.6%) for the Regimen-100 cohort and 75.5% (27.0; median 85.2%) for the Regimen-500 cohort. In the Regimen-100 and Regimen-500 cohorts, 45.3% and 55.2% had a PDC ≥ 80%, respectively. Only 23.0% and 51.6% of patients maintained TDD > 200 units for the Regimen-100 and Regimen-500 cohorts, respectively, throughout the 4 quarters after the index date. CONCLUSIONS: We observed that many patients did not maintain high-dose insulin use over time, especially those on standard U-100 insulin only. This dosing pattern appears to reflect the differences in patient characteristics, insulin needs, and adherence/persistence behavior between those on Regimen-100 and those on Regimen-500. DISCLOSURES: This study was supported by funding from Eli Lilly and Company to Humana as a collaborative research project involving employees of both companies. Chen, Brown, Fan, Taylor, and He are employees of Eli Lilly and Company. Nair and Meah are employees of Humana, which received funding to complete this research. Siadaty was an employee of Humana at the time of this study.

Effectiveness of Managing Diabetes During Ramadan Conversation Map intervention: A difference-in-differences (self-comparison) design.

BACKGROUND: Some individuals with diabetes fast during Ramadan despite medical concerns for risk of adverse outcomes. The Managing Diabetes During Ramadan Conversation Map is a self-management education group-based intervention for Muslim individuals with type 2 diabetes, specifically addressing diabetes management during Ramadan. OBJECTIVE: The aim of this study was to evaluate the effectiveness of the Managing Diabetes During Ramadan Conversation Map intervention in improving short-term clinical outcomes and reducing healthcare utilization following Ramadan. DESIGN: This was a retrospective rolling cohort study. SETTINGS: Participants were Clalit Health Services members with type 2 diabetes who participated in the intervention between 2014 and 2017 across Israel. PARTICIPANTS: This study included 1732 participants who enrolled in the intervention over the five-year study period. The cohort was mainly between the ages of 45 and 74 years (83.3%), female (71.9%), of lower socioeconomic status (92.1%), with a diabetes duration of 10 years or more (51.7%), obese (64.0%), and had never smoked (73.8%). METHODS: The data used in this study came from Clalit Health Services' electronic health records, which are integrated in a central data warehouse. We used a difference-in-differences (self-comparison) design to examine the effect of the intervention on changes in laboratory results and healthcare utilization over a six month baseline and follow-up. Mixed model linear regressions and Poisson regressions were used to estimate continuous and count outcomes, respectively. RESULTS: Post intervention, participants experienced a reduction of 8.61 mg/dL in their glucose levels (p = 0.005) and 0.34% in their HbA1c levels (p < 0.001). In a sub-group analysis of participants with HbA1c > 7%, larger reductions in glucose (17.02 mg/dL [p < 0.001]) and HbA1c (0.63% [p < 0.001]) levels were recorded. This sub-group also experienced a reduction of 4.83 mg/dL in LDL level (p = 0.007) and had 0.2 fewer primary care visits (p < 0.001). CONCLUSIONS: Participation in the Managing Diabetes During Ramadan Conversation Map improved patient glucose and HbA1c levels. A greater benefit was reported in those individuals with HbA1c > 7%. These findings hold important global health implications for the millions of individuals with type 2 diabetes for whom Ramadan can pose a challenge in disease control.

Reduced medical spending associated with increased use of a remote diabetes management program and lower mean blood glucose values.

Aims: Many new mobile technologies are available to assist people in managing chronic conditions, but data on the association between the use of these technologies and medical spending remains limited. As the available digital technology offerings to aid in diabetes management increase, it is important to understand their impact on medical spending. The aim of this study was to investigate the financial impact of a remote digital diabetes management program using medical claims and real-time blood glucose data. Materials and methods: A retrospective analysis of multivariate difference-in-difference and instrumental variables regression modeling was performed using data collected from a remote digital diabetes management program. All employees with diabetes were invited, in a phased introduction, to join the program. Data included blood glucose (BG) values captured remotely from members via connected BG meters and medical spending claims. Participants included members (those who accepted the invitation, n = 2,261) and non-members (n = 8,741) who received health insurance benefits from three self-insured employers. Medical spending was compared between people with well-controlled (BG ≤ 154 mg/dL) and poorly controlled (BG > 154 mg/dL) diabetes. Results: Program access was associated with a 21.9% (p < 0.01) decrease in medical spending, which translates into a $88 saving per member per month at 1 year. Compared to non-members, members experienced a 10.7% (p < 0.01) reduction in diabetes-related medical spending and a 24.6% (p < 0.01) reduction in spending on office-based services. Well-controlled BG values were associated with 21.4% (p = 0.03) lower medical spending. Limitations and conclusions: Remote digital diabetes management is associated with decreased medical spending at 1 year. Reductions in spending increased with active utilization. It will be beneficial for future studies to analyze the long-term effects of the remote diabetes management program and assess impacts on patient health and well-being.

The Trend of High-Dose Insulin Usage Among Patients with Diabetes in the UK: A Retrospective Study.

INTRODUCTION: Many patients with diabetes may require high-dose insulin treatment to achieve target HbA1c level, but the prevalence, disease burden, and patient characteristics of the population remain unclear. We therefore investigated people with insulin-treated diabetes in the UK from 2009 to 2013, who were prescribed high daily doses (> 200 units/day). METHODS: A retrospective analysis was conducted using the UK primary care electronic dataset from the Clinical Practice Research Datalink (CPRD). Trends of demographics, insulin dose, clinical characteristics, and annualized incidence rate of the insulin initiators were analyzed. Patients with type 1 (T1D) or type 2 diabetes (T2D) and who were prescribed insulin between 2009 and 2013 were categorized into either a low- or high-dose insulin user group. Two-sample t test and chi-square test were used for comparison of continuous variables and categorical variables, respectively. A multivariable negative binomial regression analysis with (log) person time as an offset was used to assess the impact of different covariates on incidence of high-dose insulin initiation. RESULTS: Between 2009 and 2013, 19,631 patients with diabetes were treated with insulin (T1DM, 7620; T2DM, 12,011). In 2013, 415 high-dose insulin initiators were identified (T1DM, N = 170; T2DM, N = 245). More than half were male (T1DM/T2DM, 62.4%/56.3%) and 94.1%/83.7% of T1DM/T2DM patients were prescribed an insulin analogue at high-dose insulin initiation. At 6 months, 43.6% of T1DM and 42.6% of T2DM remained to have suboptimal HbA1c level of ≥ 8% (64 mmol/mol). Overall, 15.9%/63.3% of high-dose insulin initiators (HDII) with T1DM/T2DM took oral antidiabetics. From 2009 to 2013, the estimated glomerular filtration rate worsened in both T1DM and T2DM HDII. CONCLUSION: Despite a number of patients requiring high doses of insulin in the UK, achievement of optimal HbA1c levels remains poor. Early identification of HDII is important in order to plan for alternative/adjuvant antidiabetic and lifestyle strategies to achieve optimal glycemic targets in this patient group. FUNDING: Eli Lilly and Company.

Which patients with Type 2 diabetes will have greater compliance to participation in the Diabetes Conversation Map™ program? A retrospective cohort study.

AIM: To investigate the characteristics of participants in the Diabetes Conversation Map™ (Map™) program who had higher vs. lower compliance to the program, to determine if program tailoring and monitoring is needed among these groups. METHODS: This was a retrospective cohort study of 8990 patients enrolled in the Map™ program (low compliance [attending 0-1 sessions, n = 2759] and high compliance [attending ≥2 sessions, n = 6231]). Socio-demographic, clinical, health behaviors, and healthcare utilization characteristics were extracted. Multivariable stepwise logistic regression was used as the analysis strategy. RESULTS: Those who were of higher socio-economic status (OR = 1.567, 95%CI:1.317-1.865), who lived in urban area (OR = 1.501, 95%CI:1.254-1.798), with greater frequency of primary care visits (OR = 1.012, 95%CI:1.002-1.021), with medium (OR = 1.176, 95%CI:1.013-1.365) or high oral medication adherence (OR = 1.198, 95%CI:1.059-1.356), and with a greater frequency of blood glucose tests (OR = 1.102, 95%CI:1.033-1.175) had greater odds of being in the high compliance group. Conversely, those aged 35-44 (OR = 0.538, 95%CI:0.402-0.721) and 45-54 years (OR = 0.763, 95%CI:0.622-0.937), with longer Type 2 diabetes duration (OR = 0.980, 95%CI:0.967-0.993), with higher blood glucose levels (OR = 0.999, 95%CI:0.998-1.000), and current (OR = 0.659, 95%CI:0.569-0.762) or former smokers (OR = 0.831, 95%CI:0.737-0.938) had reduced odds for being in the higher compliance group. CONCLUSIONS: Instructors in advance can target sub-groups to increase their attendance rates, and consequently improve their outcomes.

GLUCAGON PRESCRIPTIONS FOR DIABETES PATIENTS AFTER EMERGENCY DEPARTMENT VISITS FOR HYPOGLYCEMIA.

OBJECTIVE: To determine the proportion of prescription fills for glucagon within 90 days of an emergency department (ED) visit for hypoglycemia. METHODS: This was a retrospective research study of glucagon prescriptions filled after an ED visit for hypoglycemia (from January 2011 to June 2014) by people with type 1 diabetes (T1D) or type 2 diabetes (T2D) taking insulin who did not already have an unexpired glucagon prescription within the Truven Health MarketScan® Research Database. RESULTS: Less than 10% (T1D: 10.9%; T2D: 3.5%) filled a glucagon prescription after the ED visit. CONCLUSION: A substantial opportunity exists to improve care for at-risk patients with diabetes through a more consistent provision of glucagon, perhaps through the implementation of a quality metric. ABBREVIATIONS: DM = diabetes mellitus; ED = emergency department; IQR = interquartile range; T1D = type 1 diabetes; T2D = type 2 diabetes.

Estimating individualized treatment rules for ordinal treatments.

Precision medicine is an emerging scientific topic for disease treatment and prevention that takes into account individual patient characteristics. It is an important direction for clinical research, and many statistical methods have been proposed recently. One of the primary goals of precision medicine is to obtain an optimal individual treatment rule (ITR), which can help make decisions on treatment selection according to each patient's specific characteristics. Recently, outcome weighted learning (OWL) has been proposed to estimate such an optimal ITR in a binary treatment setting by maximizing the expected clinical outcome. However, for ordinal treatment settings, such as individualized dose finding, it is unclear how to use OWL. In this article, we propose a new technique for estimating ITR with ordinal treatments. In particular, we propose a data duplication technique with a piecewise convex loss function. We establish Fisher consistency for the resulting estimated ITR under certain conditions, and obtain the convergence and risk bound properties. Simulated examples and an application to a dataset from a type 2 diabetes mellitus observational study demonstrate the highly competitive performance of the proposed method compared to existing alternatives.

GLUCAGON PRESCRIPTION PATTERNS IN PATIENTS WITH EITHER TYPE 1 OR 2 DIABETES WITH NEWLY PRESCRIBED INSULIN.

OBJECTIVE: To describe glucagon prescription patterns in patients with type 1 (T1DM) or type 2 diabetes (T2DM) who received an initial insulin prescription. METHODS: Retrospective analyses were conducted with data from Truven Health MarketScan databases to assess time to glucagon prescriptions: filled within 1.5 months after index date (early) or after 1.5 months postindex (nonearly). The index date was the date of first insulin prescription between January 1, 2009 and December 31, 2011; for T2DM, without an insulin prescription in the previous 6 months; for T1DM, diabetes diagnosis preindex or within 3 months postindex. RESULTS: Analysis included 8,814 patients with T1DM and 47,051 with T2DM (49.3% and 2.4%, respectively) who had glucagon prescriptions filled. The median times to first glucagon prescription were 196 days (T1DM) and 288 days (T2DM). The rates of filling glucagon were highest in the first 1.5 months. The times to first hypoglycemia-related emergency room (ER) visit for T1DM and T2DM cohorts were initially similar for those with early glucagon versus nonearly glucagon prescriptions. After 10.8 and 2.5 months postindex, respectively, the percentage of hypoglycemia-related ER visits was lower for those with early glucagon prescriptions. CONCLUSION: Glucagon prescriptions filled for patients with diabetes who are initiating insulin are low. Patients with T1DM who were younger and healthier filled glucagon prescriptions more often; patients with T2DM who were younger and sicker and had a higher percentage of hypoglycemia-related ER visit history filled glucagon prescriptions more often. Glucagon filled early was associated with a lower incidence of hypoglycemia-related ER visits.