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Introduction Randomized controlled trials and real-world data from the USA have shown similar glycemic control with insulin glargine 300 U/ml (Gla-300) and insulin glargine 100 U/ml (Gla-100) and reduced hypoglycemia risk with Gla-300. This real-world study describes the efficacy and safety of Gla-300 and Gla-100 in patients with type 2 diabetes (T2D) in France, Spain, and Germany. Methods This retrospective chart review analysis used anonymized data for adults with T2D switching basal insulin analog (BIA) therapy to Gla-300 or Gla-100, or insulin-naïve patients initiating Gla-300 or Gla-100. Outcomes included change from baseline to 6-month follow-up in glycated hemoglobin A1c (A1C), total and severe hypoglycemia incidences and events, insulin dose, and reasons for BIA choice. Results Six hundred sixty-five physicians (33.8% Spain, 31.7% France, 34.4% Germany) provided chart data for patients switching to Gla-300 (n = 679) or Gla-100 (n = 429) or initiating Gla-300 (n = 719) or Gla-100 (n = 711). After adjustment for baseline characteristics, A1C reductions from baseline were similar for patients switching to Gla-300 or Gla-100 (− 0.87% vs. − 0.93%; p = 0.326) while those switched to Gla-300 vs. Gla-100 had a significantly greater mean reduction in hypoglycemic events (− 1.29 vs. − 0.81 events during 6 months; p = 0.012). Mean insulin doses after titration were 0.43 ± 0.36 and 0.40 ± 0.28 U/kg in Gla-300 and Gla-100 switchers, respectively. Factors that significantly influenced BIA choice included a lower risk of hypoglycemia (for Gla-300) and physician familiarity (for Gla-100). Outcomes for insulin-naïve patients were broadly similar to those of switchers. Conclusions In this real-world European study, patients with T2D who switched therapy to Gla-300 or Gla-100 had improved glycemic control and reduced hypoglycemia at 6 months, with significant hypoglycemia advantages with Gla-300. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01436-5) contains supplementary material, which is available to authorized users.

Aims To compare 12‐month clinical effectiveness of insulin glargine 300 units/mL (Gla‐300) versus first‐generation basal insulin analogues (BIAs) (insulin glargine 100 units/mL [Gla‐100] or insulin detemir [IDet]) in patients with type 2 diabetes (T2D) who were at high risk of hypoglycaemia and switched from one BIA to a different one (Gla‐300 or Gla‐100/IDet) in a real‐world setting. Methods DELIVER High Risk was a retrospective observational cohort study of 2550 patients with T2D who switched BIA to Gla‐300 (Gla‐300 switchers) and were propensity score‐matched (1:1) to patients who switched to Gla‐100 or IDet (Gla‐100/IDet switchers). Outcomes were change in glycated haemoglobin A1c (HbA1c), attainment of HbA1c goals (, In patients with type 2 diabetes at high risk of hypoglycaemia, risk of inpatient/emergency department‐related hypoglycaemia was significantly lower during 12 months after switching to insulin glargine 300 units/mL, compared with switching to insulin glargine 100 units/mL or insulin detemir.

Aims To estimate risk factors associated with early hypoglycaemia and its impact on adherence to and persistence with therapy in Medicare Part D beneficiaries with type 2 diabetes who are initiating basal insulin (BI). Materials and methods This retrospective analysis used a 5% sample of Medicare files from 2007-2013, identifying beneficiaries with type 2 diabetes initiating BI from 1 January 2008 to 31 December 2012. Early hypoglycaemia was defined as ≥1 hypoglycaemic event ≤6 months postindex. Outcomes included medication adherence and persistence over 12- and 36-month follow-up. Multivariable logistic and Cox regression analyses were conducted to examine factors associated with early hypoglycaemia and BI adherence/persistence. Results Of the 14 466 included patients, 1315 (9.1%) experienced hypoglycaemia ≤6 months after initiating BI. Factors associated with early hypoglycaemia were female sex (odds ratio [OR] 1.16 [95% confidence interval [CI] 1.02-1.32]), receipt of a low-income subsidy under Medicare Part D (OR 1.20 [95% CI 1.01-1.43]), high diabetes complication score index (OR 1.08 [95% CI 1.01-1.15]), and hypoglycaemia during the baseline period (OR 4.24 [95% CI 3.63-4.96]). At 12 months, patients with baseline hypoglycaemia were less likely to be adherent to (OR 0.81 [95% CI 0.70-0.93]) and more likely to discontinue (OR 1.33 [95% CI 1.07-1.66]) their insulin therapy. Results were similar at 36 months. Conclusions Within 6 months of BI initiation, almost 1 in 10 Medicare Part D beneficiaries experienced hypoglycaemia. Early hypoglycaemia was associated with decreased adherence to BI treatment over 12- and 36-month follow-up.

Aim To compare the second‐generation basal insulin glargine 300 units/mL (Gla‐300) and first‐generation basal insulins on glycaemic control and hypoglycaemia risk in older adults with type 2 diabetes (T2D). Materials and methods DELIVER 3 was a retrospective observational cohort study of electronic medical records. A total of 1176 older adults (aged ≥ 65 years) with T2D and ≥1 HbA1c value during 6 month baseline and 3 to 6 month follow‐up who switched from basal insulin to Gla‐300 were propensity score‐matched to 1176 older adults who switched to a first‐generation basal insulin [insulin detemir (IDet) or insulin glargine 100 units/mL (Gla‐100)]. Outcomes were follow‐up HbA1c, achievement of HbA1c

Randomized controlled trial (RCT) populations often do not reflect those typically seen in clinical practice. This retrospective, observational cohort study analysed real-world data of people with type 2 diabetes (T2DM) prescribed basal insulin analogues from electronic medical records (EMRs) in the Explorys database, which includes data from 39 integrated healthcare systems in the USA, to determine how representative selected RCTs investigating insulin glargine 300 U/mL (Gla-300) are of T2DM populations in a real-world setting. Applying eligibility criteria derived from the EDITION 1, 2, and 3 (Gla-300 vs 100 U/mL [Gla-100]) and BRIGHT (Gla-300 vs insulin degludec) RCTs, we observed that only 17% (33,345/191,218) of people captured in the real-world database would have been eligible for such trials. Those who were ineligible tended to be older, had more comorbidities and a higher baseline hypoglycaemia rate than the eligible group. Using another large US EMR database (Optum Humedica) as corroboration, we found that 15% (36,285/235,697) would have been eligible to participate in the EDITION/BRIGHT RCTs. Furthermore, only 7% (1734/24,547) would have been eligible for the CONCLUDE (insulin degludec vs Gla-300) RCT. Our findings remind us of the value of real-world data studies, complementing the results of RCTs, and providing additional insights into groups who would typically be excluded from RCTs. This article is protected by copyright. All rights reserved.

DELIVER - High Risk study compared long-term clinical outcomes for patients with T2D and high hypoglycemia risk on first-generation BIs who were switched to Gla-300 or other first-generation BIs (other switchers). Electronic medical record data from the PHIE database were used. Eligible patients (age >18 years) had ≥1 criterion for high hypoglycemia risk (age >64 years; basal-bolus insulin use; renal impairment; uncontrolled baseline A1C; sulfonylurea use; atherosclerotic cardiovascular disease; history indicating high risk, including ≥1 severe hypoglycemic episode (prior 12 months). Endpoints were A1C reduction from baseline to 9-12 months, attainment of A1C goals ( Disclosure S.D. Sullivan: Research Support; Self; Sanofi. N. Freemantle: Advisory Panel; Self; Sanofi. Research Support; Self; Akcea Therapeutics, Allergan, AstraZeneca, Ipsen Biopharmaceuticals, Inc., Sanofi, Takeda Pharmaceutical Company Limited. Speaker’s Bureau; Self; Sanofi. A.A. Menon: None. R. Gupta: None. J. Wu: Employee; Self; Sanofi US. C. Nicholls: Employee; Self; Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker’s Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. Funding Sanofi

RCTs are the gold standard for comparing therapies’ efficacy and safety but can have strict eligibility criteria and may not reflect real-life clinical practice. Electronic medical records such as those from the Predictive Health Intelligence Environment (PHIE) database may be used to assess clinical effectiveness in real-world populations missed by clinical trials. We describe here the proportion and characteristics of patients with T2DM who would have been excluded from RCTs using eligibility criteria adapted from the EDITION 1-3 and BRIGHT trials. Records from people with T2DM, with a basal insulin prescription on the index date (1 March 2015) and ≥1 HbA1c value in the previous 12 months, were evaluated. Exclusion criteria included HbA1c 10.0 %, systolic blood pressure >180 mmHg and/or diastolic blood pressure >95 mmHg, or key comorbidities (e.g., heart failure or stroke) in the previous 12 months. Of 191,218 evaluated records, 157,873 (83%) met ≥1 exclusion criterion; only 33,345 (17%) could have been included in RCTs (Table). Excluded patients were older, with more previous hypoglycemia vs. included patients and were less likely to have HbA1c between 7 and 9 %. This divergence in clinical characteristics and patient numbers highlights the need for real-world studies assessing clinical effectiveness in populations of interest typically excluded from RCTs. Disclosure D. Mauricio: Advisory Panel; Self; Merck Sharp & Dohme Corp., Sanofi. Speaker’s Bureau; Self; Almirall, S.A., Boehringer Ingelheim International GmbH, Lilly Diabetes, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Urgo Medical. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. C. Nicholls: Employee; Self; Sanofi. J. Wu: Employee; Self; Sanofi US. R. Gupta: None. A.A. Menon: None. B. Eliasson: Advisory Panel; Self; Amgen Inc., AstraZeneca, Merck Sharp & Dohme Corp. Speaker’s Bureau; Self; Boehringer Ingelheim International GmbH. Other Relationship; Self; Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Funding Sanofi

Aim To compare glycaemic control, hypoglycaemia and treatment discontinuation of insulin glargine 300 units/mL (Gla‐300) and insulin degludec (IDeg) in a real‐world study of insulin‐naïve adults with type 2 diabetes (T2D). Materials and methods DELIVER Naive D was a retrospective observational study that used electronic medical record data from the IBM Watson Health Explorys database. Insulin‐naïve adults with T2D who started Gla‐300 or IDeg between March 2015 and September 2017 were identified. Patients were active in the system for ≥12 months before and ≥6 months after starting Gla‐300 or IDeg and had HbA1c measurements during 6‐month baseline and 3‐ to 6‐month follow‐up. Outcomes were compared among 1:1 propensity score‐matched cohorts. Results In the matched cohorts (n = 638 each), the mean age was 59 years, approximately 53% were male, and mean HbA1c was 9.67% (82 mmol/mol). Mean (SD) HbA1c decreases were comparable in the Gla‐300 and IDeg cohorts (−1.67% [2.22] and −1.58% [2.20]; P = 0.51), as were HbA1c target attainment [

Hepatocellular carcinoma (HCC) is a major disease worldwide. There were 782,000 estimated new cases globallyin 2012 with the majority (76%) occurring in Asia, especially China. Although the etiologies are similar, the prevalence ofeach HCC risk factor varies in different geographic regions. In China, hepatitis B virus (HBV) infection is the major causeof HCC, whereas in Japan, US and Europe, hepatitis C virus (HCV) infection predominates. With the epidemic of obesityand diabetes, non-alcoholic fatty liver disease (NAFLD), especially its more aggressive form non-alcoholic steatohepatitis(NASH), has now become a major contributor to HCC. It is anticipated that NAFLD/NASH is likely to overtake viralhepatitis as the leading contributor to HCC in the future. Prior success in reducing HCC cases through hepatitis Bimmunization program and effective HBV treatments is likely to be offset by rising significance of NASH-associated HCC.In view of this, appropriate measures such as aggressive monitoring clinical course and prognoses of patients with HCCfrom NASH, studying pathogenesis and mechanism by which NASH promotes HCC, and developing novel intervention andtreatment strategy for these patients would be important to address this important public health challenge.

Background: When using inpatient claims data to identify hospitalizations in supplemental Medicare beneficiaries, e.g., in the MarketScan database, there is a concern that the coverage of hospitalizations in such inpatient claims may be incomplete. However, whether hospitalizations are covered by inpatient claims or not, they incur professional charges that are recorded in the professional claims data in the MarketScan Medicare database. In the context of identifying hospitalizations that might be related to heart failure (HF) in dronedarone users, we compared different approaches to identify such hospitalizations. Objective: To assess the impact of using professional claims in addition to inpatient claims on identifying hospitalizations that might be related to HF. Methods: A total of 20,834 dronedarone users who were supplemental Medicare beneficiaries between July 2009 (launch date in US) and December 2012 were identified in the MarketScan database. The hospitalizations that might be related to HF within 30 days prior to initiating dronedarone were identified by searching (1) inpatient claims and (2) both inpatient and professional claims using related ICD-9-CM diagnosis codes for HF and Current Procedural Terminology codes for hospitalizations. Results: A total of 1,162 patients who had HF hospitalizations within 30 days prior to initiating dronedarone were identified by searching inpatient claims between July 2009 and December 2012. Supplementing with professional claims identified an additional 177 patients who had HF hospitalizations, increasing the total number to 1,339. Therefore, 13.2% (177/1,399) of the patients who had HF hospitalizations could only be identified in professional claims. Thus, the prevalence of hospitalizations that might be related to HF within 30 days prior to initiating dronedarone was 5.6% (1,162/20,834; 95% confidence interval (CI): 5.3 - 5.9%) when hospitalizations were identified using inpatient claims alone. Adding professional claims in the search algorithm, the prevalence of HF hospitalizations was 6.4% (1,339/20,834, 95% CI: 6.1 - 6.8%). Conclusions: Using professional claims, in addition to inpatient claims, can improve the identification of hospitalizations that might be related to HF.

Antipsychotic drug therapy is the cornerstone of treatment of persons with schizophrenia. Because most antipsychotics are metabolized by the hepatic cytochrome P450 system, concomitant use of an antipsychotic and medications that are competitively metabolized by the same system may cause a potentially harmful drug-drug interaction. This study used a large state's Medicaid claims database to examine the proportion of patients exposed to such interactions and the risk factors associated with exposure.Claims from January 2000 through December 2003 for adult patients with a diagnosis of schizophrenia and at least one prescription for an antipsychotic (N=27,909) were examined for pairs of medications identified as potentially causing moderate or severe adverse drug effects. Logistic regression models were estimated to determine potential risk factors associated with exposure to the interaction pairs.A total of 6,417 (23%) patients were exposed to 14,213 potentially harmful interactions; 4,725 patients had at least one exposure from the same pharmacy, and 4,032 patients were exposed by the same physician. The greatest number of exposures (N=1,353) to potentially harmful combinations involved olanzapine and haloperidol. Patients prescribed risperidone were most likely to be exposed to an interaction (13.1%), followed by patients prescribed olanzapine (10.3%), quetiapine (3.3%), and clozapine (3.2%). A higher risk of exposure was associated with being female (odds ratio [OR]=.94), being white (OR=1.43), having depression (OR=1.21), or having impulse-control disorder (OR=1.98).Interventions by physicians and pharmacies to reduce the prescribing and dispensing of potentially harmful pairs of medications to patients with schizophrenia are recommended.

Background A reporting association of risperidone with pituitary tumors has been observed. Because such tumors are highly prevalent, there may be other reasons why they were revealed in association with risperidone treatment. We assessed two potential explanations: disproportionately more prolactin assessment and head/brain imaging in risperidone-treated patients vs patients treated with other antipsychotics. Methods Treatment episodes with risperidone, clozapine, olanzapine, quetiapine, ziprasidone, aripiprazole, haloperidol, perphenazine and 'other typical' antipsychotics were identified in two databases (large commercial, Medicaid). Comparisons used proportional hazards regression to determine whether prolactin testing was disproportionate with risperidone, regardless of prior potentially prolactin-related adverse events (PPAEs). Logistic regression determined whether magnetic resonance imaging (MRI)/computed tomography (CT) were disproportionate in risperidone-treated patients vs other patients, regardless of hyperprolactinemia or PPAEs. In each regression, the 'other typical' antipsychotic category served as the comparator. Regression models controlled for age, gender, and other factors. Results Altogether, 197,926 treatment episodes were analyzed (63,878 risperidone). Among patients with or without preceding PPAEs, risperidone treatment was associated with a significantly greater likelihood of prolactin assessment (hazard ratio (HR) 1.34, 95% confidence interval (CI) = 1.09 to 1.66, p = 0.007). Among patients with hyperprolactinemia or PPAEs, those treated with risperidone (odds ratio (OR) 1.66, 95% CI 1.23 to 2.23, p = 0.001) or ziprasidone (OR 1.66, 95% CI 1.06 to 2.62, p = 0.028) had a higher likelihood of MRI/CT. Conclusion Risperidone-treated patients are more likely to undergo prolactin assessment regardless of prior PPAEs, and more likely to undergo MRI/CT in association with hyperprolactinemia or PPAEs. Thus, a predisposition for more evaluations in risperidone-treated patients may contribute to disproportionate identification and reporting of prevalent pituitary adenoma.

Background :Wernicke’s encephalopathy (WE) is an acute neuropsychiatric syndrome resulting from thiamine deficiency. This neurological deterioration is potentially dangerous because it predisposes the patient to hypothermia and decreased immunity. Cancer patients are at high risk of WE due to chronic malnutrition, chemotherapy-induced nausea and vomiting, and consumption of thiamine by rapidly growing tumors. Very little published research addresses the risk of WE in patients with myeloproliferative neoplasm (MPN). Objectives: To estimate the incidence of WE among patients with MPN, and compare it with those without MPN. Methods: Patients with a diagnosis of MPN, including polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF) were identified from 1/1/2003 to 03/31/2013 using the US MarketScan database. The control cohort consisted of a random sample matched to the MPN cohort by age and gender in a 1:1 ratio. Diagnosis of WE was ascertained using ICD-9-CM 265.0, 265.1, 291.1, 294.0 or J code J3411. The two study cohorts were followed for WE from the index date. Cox proportional hazards modeling was used to compare the rates between two cohorts and also control for confounding variables. Results: A total of 39,761 MPN patients, including PV (51%), ET (42%), post-PV MF (0.2%), post-ET MF (1%), and PMF (2.8%) were identified. Approximately 27% of them were > 65 years of age, and 51% were male. Patients with MPN had higher rates of WE, compared to those without MPN (MPN vs. non-MPN: 1.09 vs. 0.39/1000 person-year, hazard ratio = 2.19, 95% confidence interval 1.43-3.34). The incidence rate of WE was higher in males (male vs. female: 0.93 vs. 0.55/1000 person-year). No specific pattern was observed in age subgroups for both cohorts (e.g. MPN: age 70 = 0 vs. 0.85 vs. 1.09 vs. 1.16 vs. 0.72 vs. 0.86/1000 person-year). Conclusions: Patients with MPN had higher incidence rates of WE, compared to those without MPN. Given the potentially dangerous outcomes associated with WE, physicians who care for patients with MPN should be aware of the risk of WE in this population. Disclosures Wu: Sanofi: Employment. Mirza:Sanofi: Employment. Partisano:Sanofi: Employment. Gallagher:Sanofi: Postdoctoral Fellow Other. Vaze:Sanofi: Employment. Zhang:Sanofi: Employment. Gallagher:Sanofi: Employment. Lin:Sanofi: Employment. Juhaeri:Sanofi: Employment.