A global study of the unmet need for glycemic control and predictor factors among patients with type 2 diabetes mellitus who have achieved optimal fasting plasma glucose control on basal insulin.

BACKGROUND: This study used data from different sources to identify the extent of the unmet need for postprandial glycemic control in patients with type 2 diabetes mellitus (T2DM) after the initiation of basal insulin therapy in Europe, Asia Pacific, the United States, and Latin America. METHODS: Different levels of evidence were used as available for each country/region, with data extracted from seven randomized controlled trials (RCTs), three clinical trial registries (CTRs), and three electronic medical record (EMR) databases. Glycemic status was categorized as "well controlled" (glycated hemoglobin [HbA1c ] at target [<7%]), "residual hyperglycemia" (fasting plasma glucose [FPG] but not HbA1c at target [FPG <7.2/7.8 mmol/L, <130/140 mg/dL, depending on country-specific recommendations]), or "uncontrolled" (both FPG and HbA1c above target). Predictor factors were identified from the RCT data set using logistic regression analysis. RESULTS: RCT data showed that 16.9% to 28.0%, 42.7% to 54.4%, and 16.9% to 38.1% of patients with T2DM had well-controlled glycemia, residual hyperglycemia, and uncontrolled hyperglycemia, respectively. In CTRs, respective ranges were 21.8% to 33.6%, 31.5% to 35.6%, and 30.7% to 46.8%, and in EMR databases were 4.4% to 21.0%, 23.9% to 31.8%, and 53.6% to 63.8%. Significant predictor factors of residual hyperglycemia identified from RCT data included high baseline HbA1c (all countries/regions except Brazil), high baseline FPG (United Kingdom/Japan), longer duration of diabetes (Brazil), and female sex (Europe/Latin America). CONCLUSIONS: Irrespective of intrinsic differences between data sources, 24% to 54% of patients with T2DM globally had residual hyperglycemia with HbA1c not at target, despite achieving FPG control, indicating a significant unmet need for postprandial glycemic control.

Update of Incidence, Prevalence, Survival, and Initial Treatment in Patients With Non-Small Cell Lung Cancer in the US.

IMPORTANCE: Updated estimates of non-small cell lung cancer (NSCLC) in the US are needed. OBJECTIVE: To calculate the most recent epidemiologic estimates of NSCLC in the US. DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional epidemiological analysis used the most recently released data from US cancer registries. The population-based US Cancer Statistics (USCS) database (2010-2017), comprised of the Surveillance, Epidemiology, and End Results (SEER) program and the National Program of Cancer Registries (NPCR) (collectively, SEER-NPCR) provided the NSCLC incidence estimate. The SEER-18 database provided data for incidence, prevalence, survival, and initial treatment by NSCLC stage. Adults aged 18 years or older diagnosed with NSCLC identified by International Classification of Diseases for Oncology, Third Edition, morphology codes were included. MAIN OUTCOMES AND MEASURES: Annual age-adjusted NSCLC incidence per 100 000 persons; annual prevalence per 100 000 persons; survival rate; initial treatment. Due to database release delays, incidence data were available through 2017, and other parameters through 2016. The analysis was conducted from June 2020 to July 2020. RESULTS: There were 1.28 million new NSCLC cases recorded during 2010 to 2017 in the US (SEER-NPCR: 53% male; 67% ≥ 65 years). From 2010 to 2017, NSCLC incidence per 100 000 decreased from 46.4 to 40.9 overall (age <65 years: 15.5 to 13.5; age ≥65 years: 259.9 to 230.0); the incidence of stage II, IIIA, and IIIB NSCLC was stable, and stage IV decreased slightly from 21.7 to 19.6, whereas stage I incidence increased from 10.8 to 13.2. From 2010 to 2016, NSCLC prevalence per 100 000 increased from 175.3 to 198.3 (nationwide projection of SEER-18); prevalence increased among younger patients (77.5 to 87.9) but decreased among older patients (825.1 to 812.4). Period survival analysis found that 26.4% of patients survived 5 years, which is higher than previously reported. The proportion of stage I NSCLC treated with radiation as single initial treatment rose markedly from 14.7% in 2010 to 25.7% in 2016. Patients with stage IV NSCLC aged 65 years or older were most likely to be untreated (38.3%). CONCLUSIONS AND RELEVANCE: The findings of this cross-sectional epidemiological analysis suggest that the increased incidence of stage I NSCLC at diagnosis likely reflected improved evaluation of incidental nodules. A smaller proportion of patients aged 65 years or older with stage IV NSCLC were treated. Earlier detection and availability of effective treatments may underlie increased overall NSCLC prevalence, and higher than previously reported survival.

Health Care Utilization and Expenditures Following Diagnosis of Nontuberculous Mycobacterial Lung Disease in the United States.

BACKGROUND: Nontuberculous mycobacterial lung disease (NTMLD) is an important public health concern that has been increasing in prevalence. OBJECTIVES: To (a) describe hospitalizations and health care expenditures among patients with newly diagnosed NTMLD and (b) estimate attributable hospitalizations and expenditures to NTMLD in the United States. METHODS: In this matched cohort study, patients and controls were identified from a large U.S. national managed care insurance database containing aggregated health claims of up to 18 million fully covered members annually. NTMLD was defined based on diagnostic claims for NTMLD on ≥ 2 separate occasions ≥ 30 days apart between 2007 and 2016. Thirty-six months of continuous enrollment (12 months before and 24 months after the first diagnostic claim) was required. Health care utilization and standardized health care expenditures were summarized over 12 months before NTMLD diagnosis and for 2 subsequent years. The percentage of patients that were hospitalized in years 1 and 2 was evaluated using a generalized mixed effects model with adjustment for baseline hospitalizations, Charlson Comorbidity Index, and baseline diseases. A general estimating equation model was used to evaluate health care expenditures. RESULTS: There were 1,039 patients in the NTMLD cohort and 2,078 in the control cohort. NTMLD patients had a 55.0% risk of hospitalization in year 1 (95% CI = 45.4-64.3) and a 38.8% risk in year 2 (95% CI = 30.0-48.4). The adjusted risk of hospitalization was significantly higher in the NTMLD group compared with the control group in year 1 (OR = 4.64; 95% CI = 3.74-5.76; P < 0.001) and year 2 (OR = 2.26; 95% CI = 1.78-2.87; P < 0.001). Year 1 adjusted mean health care expenditures for the total NTMLD patient population were $72,475 (95% CI = $58,510-$86,440) and for the matched control population were $28,405 (95% CI = $8,859-$47,950), with a difference of $44,070 (95% CI = $27,132-$61,008; P < 0.001). Year 2 adjusted mean expenditures for the overall NTMLD patient group were $48,114 (95% CI = $31,722-$64,507) and for the matched control group were $28,990 (95% CI = $9,429-$48,552), with a difference of $19,124 (95% CI = $7,865-$30,383; P < 0.001). CONCLUSIONS: Patients with NTMLD have a significantly greater risk of hospitalization and higher total health care expenditures than matched control patients without NTMLD. DISCLOSURES: This study was financially sponsored by Insmed. Marras reports fees from Insmed, Astra Zeneca, RedHill, and Horizon, all outside the current work. Mirsaeidi has nothing to disclose. Eagle, Q. Zhang, Chou, and Leuchars are employees of Insmed. R. Zhang is a contracted consultant at Insmed. The views expressed here are those of the authors and are not to be attributed to their respective affiliations.

Relative risk of all-cause mortality in patients with nontuberculous mycobacterial lung disease in a US managed care population.

RATIONALE: The risk of all-cause mortality of nontuberculous mycobacterial lung disease (NTMLD) in the United States (US) population is not well established. OBJECTIVES: This study aims to assess the public health burden of NTMLD in the US by comparing the relative risk of all-cause mortality in the NTMLD population with an age- and sex-matched cohort from the general population. METHODS: Patients with physician claims for NTMLD (ICD-9 0.031; ICD-10 A31.0) were identified between 2007 and 2016 from a large US national managed care insurance plan covering approximately 15-18 million members annually. A control group with no NTMLD ICD-9 or 10 codes was randomly selected from the general population and matched 3:1 to the NTMLD sample according to birth year, gender, and insurance benefit coverage. The date of first NTMLD diagnosis of each patient was assigned to the matched controls as the index date. The Cox proportional hazard method compared survival between cohorts, adjusting for demographic factors and baseline comorbidities. RESULTS: A total of 2005 patients with NTMLD and 6014 controls were identified, with a mean follow-up duration of 3.4 years and 3.7 years, respectively. The NTMLD group had substantially higher proportions of patients with asthma (23.3% versus 3.5%), bronchiectasis (36.5% versus 0.1%), COPD (52.0% versus 5.9%), arrhythmia (22.6% versus 6.5%), coronary artery disease (18.5% versus 6.6%), heart failure (11.9% versus 4.1%), and cancer (18.5% versus 5.0%). The unadjusted rate of all-cause mortality from the index date was 20.7 per 1000 person-years in the NTMLD group vs 5.6 per 1000 person-years in the control group (rate ratio = 3.73; 95% CI: 2.93-4.75). Multivariable Cox regression, adjusted for the above variables as well as all other important baseline covariates, showed a doubling risk of all-cause mortality (hazard ratio [HR] = 2.06; CI: 1.52-2.79; P < 0.001) in the NTMLD vs control group. CONCLUSIONS: All-cause mortality, adjusted for other factors, more than doubled with NTMLD compared with an age-sex-matched control group in a large US national managed care insurance plan.

Economic burden of hypoglycemia with basal insulin in type 2 diabetes.

OBJECTIVES: To assess the impact of hypoglycemia and potential underlying factors of economic burden in patients with type 2 diabetes (T2D) who are initiating basal insulin therapy. STUDY DESIGN: This retrospective cohort study combined commercial insurance and Medicare Advantage data from the Clinformatics Data Mart. METHODS: Adults with T2D on oral antidiabetes drugs initiating basal insulin (n = 18,918) were assessed at baseline (12 months prior to insulin initiation) and follow-up (1 and 2 years). The population was stratified by whether or not patients experienced hypoglycemia during year 1 after insulin initiation. Outcomes included hypoglycemia rate, complications, comorbidities, and adjusted economic burden (primary). RESULTS: There were 1683 (8.9%) patients in the hypoglycemia group and 17,235 (91.1%) in the no-hypoglycemia group. During year 1, the estimated rate of hypoglycemia events was 0.412 per member per year. Baseline hypoglycemia was the strongest predictor of subsequent hypoglycemia. The hypoglycemia group was older, with a significantly greater clinical and economic burden at baseline; these differences persisted during follow-up. In the hypoglycemia group, for every 100 members per year, 463 hypoglycemia episodes were recorded, with a mean cost per episode of $986. Hypoglycemia-related medical expenses accounted for 12.6% ($4563/$36,272) of total healthcare expenditure, with hypoglycemia-related hospitalizations accounting for 19.7% ($2602/$13,191) of total hospitalization expenditure. CONCLUSIONS: Compared with patients with no hypoglycemia-related claims in year 1 after basal insulin initiation, patients with a hypoglycemia-related claim had a greater burden of complications and comorbidity associated with significantly higher healthcare utilization and cost at baseline; these persisted during follow-up.

Safety and efficacy of insulin glargine 300 u/mL compared with other basal insulin therapies in patients with type 2 diabetes mellitus: a network meta-analysis.

OBJECTIVE: To compare the efficacy and safety of a concentrated formulation of insulin glargine (Gla-300) with other basal insulin therapies in patients with type 2 diabetes mellitus (T2DM). DESIGN: This was a network meta-analysis (NMA) of randomised clinical trials of basal insulin therapy in T2DM identified via a systematic literature review of Cochrane library databases, MEDLINE and MEDLINE In-Process, EMBASE and PsycINFO. OUTCOME MEASURES: Changes in HbA1c (%) and body weight, and rates of nocturnal and documented symptomatic hypoglycaemia were assessed. RESULTS: 41 studies were included; 25 studies comprised the main analysis population: patients on basal insulin-supported oral therapy (BOT). Change in glycated haemoglobin (HbA1c) was comparable between Gla-300 and detemir (difference: -0.08; 95% credible interval (CrI): -0.40 to 0.24), neutral protamine Hagedorn (NPH; 0.01; -0.28 to 0.32), degludec (-0.12; -0.42 to 0.20) and premixed insulin (0.26; -0.04 to 0.58). Change in body weight was comparable between Gla-300 and detemir (0.69; -0.31 to 1.71), NPH (-0.76; -1.75 to 0.21) and degludec (-0.63; -1.63 to 0.35), but significantly lower compared with premixed insulin (-1.83; -2.85 to -0.75). Gla-300 was associated with a significantly lower nocturnal hypoglycaemia rate versus NPH (risk ratio: 0.18; 95% CrI: 0.05 to 0.55) and premixed insulin (0.36; 0.14 to 0.94); no significant differences were noted in Gla-300 versus detemir (0.52; 0.19 to 1.36) and degludec (0.66; 0.28 to 1.50). Differences in documented symptomatic hypoglycaemia rates of Gla-300 versus detemir (0.63; 0.19 to 2.00), NPH (0.66; 0.27 to 1.49) and degludec (0.55; 0.23 to 1.34) were not significant. Extensive sensitivity analyses supported the robustness of these findings. CONCLUSIONS: NMA comparisons are useful in the absence of direct randomised controlled data. This NMA suggests that Gla-300 is also associated with a significantly lower risk of nocturnal hypoglycaemia compared with NPH and premixed insulin, with glycaemic control comparable to available basal insulin comparators.

Treatment persistence after initiating basal insulin in type 2 diabetes patients: A primary care database analysis.

AIMS: To compare persistence and its predictors in type 2 diabetes patients in primary care, initiating either basal supported oral therapy (BOT) or intensified conventional therapy (ICT) with glargine, detemir, or NPH insulin. METHODS: In the BOT cohort, 1398 glargine (mean age: 68 years), 292 detemir (66 years), and 874 NPH (65 years) users from 918 practices were retrospectively analyzed (Disease Analyzer, Germany: 2008-2012). The ICT group incorporated 866 glargine (64 years), 512 detemir (60 years), and 1794 NPH (64 years) new users. Persistence was defined as proportion of patients remaining on the initial basal insulin (glargine, detemir and NPH insulin) over 2 years. Persistence was evaluated by Kaplan-Meier curves (log-rank tests) and Cox regression adjusting for age, sex, diabetes duration, antidiabetic co-therapy, comorbidities, specialist care, and private health insurance. RESULTS: In BOT, two-year persistence was 65%, 53%, and 59% in glargine, detemir, and NPH users, respectively (p<0.001). In ICT, persistence was higher without differences between groups: 84%, 85%, 86% in glargine, detemir, and NPH, respectively (p=0.536). In BOT, detemir and NPH users were more likely to discontinue basal insulin compared with glargine (detemir vs. glargine: adjusted Hazard Ratio; 95% CI: 1.56; 1.31-1.87; NPH vs. glargine: 1.22; 1.07-1.38). Heart failure (1.39; 1.16-1.67) was another predictor of non-persistence, whereas higher age (per year: 0.99; 0.98-0.99), metformin (0.61; 0.54-0.69), and sulfonylurea co-medication (0.86; 0.77-0.97) were associated with lower discontinuation. CONCLUSIONS: In BOT, treatment persistence among type 2 diabetes patients initiating basal insulin is influenced by type of insulin, antidiabetic co-medication, and patient characteristics.