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Kaan Tunceli,1 Changgeng Zhao,1 Michael J Davies,2 Kimberly G Brodovicz,3 Charles M Alexander,4 Kristy Iglay,1 Larry Radican1 1Global Health Outcomes, Merck & Co, Inc, Whitehouse Station, NJ, USA; 2Global Scientific and Medical Publications, Merck & Co, Inc, Whitehouse Station, NJ, USA; 3Global Epidemiology, Merck & Co, Inc, Whitehouse Station, NJ, USA; 4Global Medical Affairs, Merck & Co, Inc, Whitehouse Station, NJ, USA Aim: To estimate the rate of adherence to oral antihyperglycemic monotherapy for patients with type 2 diabetes in the US and describe factors associated with adherence in these patients.Materials and methods: In this retrospective cohort analysis, patients aged 18 years or older with a type 2 diabetes diagnosis received between 1 January 2007 and 31 March 2010 were identified using a large US-based health care claims database. The index date was defined as the date of the first prescription for oral antihyperglycemic monotherapy during this period. Patients had to have continuous enrollment in the claims database for 12 months before and after the index date. Adherence was assessed using proportion of days covered (PDC) and an adjusted logistic regression analysis was performed to evaluate factors associated with adherence (PDC ≥80%).Results: Of the 133,449 eligible patients, the mean age was 61 years and 51% were men. Mean PDC was 75% and the proportion of patients adherent to oral antihyperglycemic monotherapy was 59%. Both mean PDC and PDC ≥80% increased with increasing age and the number of concomitant medications, and were slightly higher in men compared to women. Results from the logistic regression demonstrate an increased likelihood of non-adherence for patients who were younger, new to therapy, on a twice-daily dose, female, or on fewer than three concomitant medications compared to their reference groups. Higher average daily out-of-pocket pharmacy expense was also associated with an increased likelihood of non-adherence. All results were statistically significant (P

A Brett Hauber,1 Steven Han,2,3 Jui-Chen Yang,1 Ira Gantz,2 Kaan Tunceli,2 Juan Marcos Gonzalez,1 Kimberly Brodovicz,2 Charles M Alexander,2 Michael Davies,2 Kristy Iglay,2 Qiaoyi Zhang,2 Larry Radican2 1Health Preference Assessment, Research Triangle Institute (RTI) Health Solutions, Research Triangle Park, NC, USA; 2Merck Sharp and Dohme Corporation, Whitehouse Station, NJ, USA; 3Temple University, Philadelphia, PA, USA Purpose: To quantify willingness-to-pay (WTP) for reducing pill burden and dosing frequency among patients with type 2 diabetes mellitus (T2DM), and to examine the effect of dosing frequency and pill burden on likely medication adherence. Patients and methods: Participants were US adults with T2DM on oral antihyperglycemic therapy. Each patient completed an online discrete-choice experiment (DCE) with eight choice questions, each including a pair of hypothetical medication profiles. Each profile was defined by reduction in average glucose (AG), daily dosing, chance of mild-to-moderate stomach problems, frequency of hypoglycemia, weight change, incremental risk of congestive heart failure (CHF), and cost. Patients were asked to rate their likely adherence to the profiles presented in each question. Choice questions were based on a predetermined experimental design. Choice data were analyzed using random-parameters logit. Likely treatment adherence was analyzed using a Heckman two-stage model. Results: Of the 1,114 patients who completed the survey, 90 had lower dosing burden (

Abstract Objective: To assess the impact of hypoglycemia on clinical outcomes among hospitalized, insulin-treated patients. Methods: In a retrospective study, hospitalizations in 2005-2007 were identified from a US inpatient electronic medical records database. All encounters for insulin-treated patients with valid blood glucose measurement were included, except for those with a length of stay <24 hours or >30 days. In an encounter-based analysis, associations between hypoglycemic (glucose <=70 mg/dL) or severe hypoglycemic (glucose <=50 mg/dL) episodes and inpatient mortality, ischemic events, neurologic complications, and length of stay were evaluated. Results: Among 107,312 admissions, hypoglycemia occurred in 21,561 (20%) and severe hypoglycemia in 7539 (7%). Inpatient mortality occurred in 6.5% of hospitalizations with hypoglycemia and 3.8% of those without (p < 0.001). Inpatient mortality occurred in 7.6% of hospitalizations with a severe hypoglycemic event. Ischemic events (8.1 vs. 8.0%) and neurologic complications (3.8 vs. 3.7%) were similar in hospitalizations with and without a hypoglycemic event, respectively. In multivariate logistic regression analyses adjusting for age, gender, and selected comorbidities, hypoglycemia was associated with a significant increase in inpatient mortality risk (adjusted odds ratio (OR) = 1.66 [95% CI: 1.55, 1.78]). Similar results were observed with severe hypoglycemia (adjusted OR = 1.44 [1.38, 1.52]). Length of stay was increased in hospitalizations with hypoglycemia (median [interquartile range]: 8.2 days [4.9, 13.9] vs. 5.2 days [3.1, 8.3]; p < 0.0001). Limitations: Due to the nature of the data source, some data of interest were not available, including insulin dose and dose regimen, outpatient medical histories (including diabetes history), pre-hospitalization medications, and cause of death. Conclusions: Hypoglycemia was common among hospitalized patients receiving insulin and, while a direct causal relationship cannot be assumed, was associated with an increased risk of inpatient mortality and increased length of hospital stay. Hypoglycemia is an undesirable event and efforts to minimize in-hospital hypoglycemic events are warranted across the spectrum of hospitalized patients. [ABSTRACT FROM AUTHOR]

Abstract Objective: To compare the incidence of symptomatic hypoglycemia between sitagliptin and sulfonylurea in Muslim patients with type 2 diabetes who fasted during Ramadan. Methods: In a multicenter, pragmatic, randomized study, patients with type 2 diabetes were recruited from clinical centers in India (n = 765) and Malaysia (n = 105). Eligible patients (age >= 18 yrs) expressed their intention to daytime fast during Ramadan, were treated with a stable dose of sulfonylurea with or without metformin for >=3 months prior to screening visit, and had an HbA(1c) <= 10%. Patients were randomized in a 1:1 ratio to either switch to sitagliptin 100 mg q.d. or remain on their pre-study sulfonylurea. Daily diary cards were completed to document information on hypoglycemic symptoms and complications. The primary endpoint was the overall incidence of symptomatic hypoglycemia during Ramadan. Results: Of the 870 patients randomized, 848 (n = 421 for sitagliptin and 427 for sulfonylurea) returned >=1 completed diary card and were included in the analysis. The proportion of patients who recorded >=1 symptomatic hypoglycemic event during Ramadan was lower with sitagliptin (3.8%) compared to sulfonylurea (7.3%). The risk of symptomatic hypoglycemia was significantly lower with sitagliptin (risk ratio [95% CI] = 0.52 [0.29, 0.94]; p = 0.028). By country, the proportions of patients who recorded >=1 symptomatic hypoglycemic event during Ramadan were 4.1% vs. 7.7% in India and 1.9% vs. 3.8% in Malaysia for sitagliptin and sulfonylurea, respectively. No patient discontinued treatment due to a hypoglycemic event. One patient on sitagliptin and seven on sulfonylurea had an event that required non-medical assistance. No events required medical assistance. Both treatments were generally well tolerated. Limitations: Symptomatic hypoglycemic events did not require a confirmatory blood glucose measurement, which may have overestimated hypoglycemic events. Measures of glycemic control and body weight were not assessed. Conclusion: Switching antihyperglycemic treatment to sitagliptin from a sulfonylurea reduced the risk of symptomatic hypoglycemia by approximately 50% for Muslim patients with type 2 diabetes who fasted during Ramadan. Clinical trial registration: Clinicaltrials.gov: NCT01340768. [ABSTRACT FROM AUTHOR]

Abstract Objectives: To compare effects of fixed-dosed combinations (FDCs) and coadministered dual therapy (CDT) of antihyperglycemic agents on glycemic control (i.e., HbA(1c)) and medication adherence. Methods: A systematic literature review and meta-analysis were performed to compare the HbA(1c) response and medication adherence between the two drug regimens. Selected articles were limited to studies that compared equivalent drug components within FDC and CDT. Searches used PubMed, Embase, Web of Knowledge, and Cochrane databases. The search results were independently screened and reviewed by two authors (SH, KI). Of the 1246 identified abstracts, 152 articles were reviewed, and ten met the inclusion criteria. Results were extracted and pooled in a meta-analysis, using a random-effects model. Cohort comparisons were described as mean differences (MDs) with 95% confidence intervals (CIs). Results: The ten articles that met the inclusion criteria had a total study size of 70,573 patients. Four articles reported HbA(1c) results, which had a total of five cohort comparisons of FDC and CDT use. The meta-analysis revealed a significantly greater HbA(1c) reduction with FDC (MD = -0.53% [95% CI: -0.78, -0.28]; p < 0.0001). Eight studies evaluated medication adherence (measured as medication possession ratio [MPR]). Of the eight studies reporting MPR results, a total of 12 cohort comparisons were made and were further divided into three subgroups based on comparison types. Five comparisons described MPR for FDC versus CDT cohorts, with significantly higher MPR with FDC (MD = 8.6% [95% CI: 1.6, 15.6]; p = 0.0162]). Four comparisons examined patients who switched from monotherapy to FDC or CDT, with higher MPR for patients who switched to FDC (MD = 7.7% [95% CI: 5.7, 9.6]; p < 0.0001). Three comparisons described results for patients who switched from CDT to FDC or stayed on CDT, with higher MPR for patients who switched to FDC (MD = 5.0% [95% CI: 3.1, 6.8]; p < 0.0001). Limitations: A limited number of published studies were available for this meta-analysis and all of those included were observational studies. There was heterogeneity between studies in the statistical methods used to control for confounding variables and differing population characteristics. Conclusions: In a meta-analysis, use of FDCs with antihyperglycemic agents was associated with lower HbA(1c) and higher MPR values compared to CDT use in patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Objective: To extend follow-up of 14,455 workers from 1990 to 2000, and evaluate mortality risk from exposure to trichloroethylene (TCE) and other chemicals.Methods: Multivariable Cox models were used to estimate relative risk (RR) for exposed versus unexposed workers based on previously developed exposure surrogates.Results: Among TCE-exposed workers, there was no statistically significant increased risk of all-cause mortality (RR = 1.04) or death from all cancers (RR = 1.03). Exposure-response gradients for TCE were relatively flat and did not materially change since 1990. Statistically significant excesses were found for several chemical exposure subgroups and causes and were generally consistent with the previous follow-up.Conclusions: Patterns of mortality have not changed substantially since 1990. Although positive associations with several cancers were observed, and are consistent with the published literature, interpretation is limited due to the small numbers of events for specific exposures. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Case-control studies suggest hydrocarbons increase end-stage renal disease (ESRD) risk. No cohort studies have been conducted. METHODS: An occupational database was matched to the U.S. Renal Data System, and the outcome of all-cause ESRD was examined using multivariable Cox regression. Sixteen individual hydrocarbons were studied, although exposures were not mutually exclusive. RESULTS: For the 1973-2000 period, there was an approximate twofold increased risk of ESRD among workers exposed to trichloroethylene, 1,1,1-trichloroethane, and JP4 gasoline compared with unexposed subjects (all P < 0.05). Relative risk was greater than unity (P > 0.05) for several other hydrocarbons. Associations attenuated (all P > 0.05) when 2001-2002 data were included in the analyses. CONCLUSIONS: Certain hydrocarbons may increase all-cause ESRD risk. Uncertainty regarding the mechanism for increased risk and the observed attenuation in risk in 2001-2002, as well as the overlap of exposures, complicates interpretation. Additional research is needed. [ABSTRACT FROM AUTHOR]