Kristy Iglay

Prevalence and co-prevalence of comorbidities among patients with type 2 diabetes mellitus

Abstract Objective: Patients with type 2 diabetes (T2DM) often have multiple comorbidities which may impact the selection of antihyperglycemic therapies. The purpose of this study was to quantify the prevalence and co-prevalence of common comorbidities. Research design and methods: A retrospective study was conducted using the Quintiles Electronic Medical Record database. Adult patients with T2DM who had ≥1 encounter from July 2014 to June 2015 (index period) with ≥1 year medical history available were included. The index date was defined as the most recent encounter date during the 1 year index period. Main outcome measures: Comorbid conditions were assessed using all data available prior to and including the index date. Patient characteristics, laboratory measures, and comorbidities were summarized via descriptive analyses, overall and by subgroups of age (<65, 65–74, 75+ years) and gender. Results: Of the 1,389,016 eligible patients, 53% were female and the median age was 65 years. 97.5% of patients had at least one comorbid condition in addition to T2DM and 88.5% had at least two. The comorbidity burden tended to increase in older age groups and was higher in men than women. The most common conditions in patients with T2DM included hypertension (HTN) in 82.1%; overweight/obesity in 78.2%; hyperlipidemia in 77.2%; chronic kidney disease (CKD) in 24.1%; and cardiovascular disease (CVD) in 21.6%. The highest co-prevalence was demonstrated for the combination of HTN and hyperlipidemia (67.5%), followed by overweight/obesity and HTN (66.0%), overweight/obesity and hyperlipidemia (62.5%), HTN and CKD (22.4%), hyperlipidemia and CKD (21.1%), HTN and CVD (20.2%), hyperlipidemia and CVD (20.1%), overweight/obesity and CKD (19.1%) and overweight/obesity and CVD (17.0%). Limitations: Limitations include the potential for misclassification/underreporting due to the use of diagnostic codes, drug codes, or laboratory measures for identification of medical conditions. Conclusions: The vast majority of patients with T2DM have multiple comorbidities. To ensure a comprehensive approach to patient management, the presence of multimorbidity should be considered in the context of clinical decision making.

Glycemic effectiveness and medication adherence with fixed-dose combination or coadministered dual therapy of antihyperglycemic regimens: a meta-analysis.

Abstract Objectives: To compare effects of fixed-dosed combinations (FDCs) and coadministered dual therapy (CDT) of antihyperglycemic agents on glycemic control (i.e., HbA1c) and medication adherence. Methods: A systematic literature review and meta-analysis were performed to compare the HbA1c 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 HbA1c results, which had a total of five cohort comparisons of FDC and CDT use. The meta-analysis revealed a significantly greater HbA1c 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 HbA1c and higher MPR values compared to CDT use in patients with type 2 diabetes.

Meta-analysis of studies examining medication adherence, persistence, and discontinuation of oral antihyperglycemic agents in type 2 diabetes

Abstract Objective: To estimate overall rates of adherence, persistence, and discontinuation for patients with type 2 diabetes mellitus (T2DM) prescribed oral antihyperglycemic agents (OAHAs) by combining results of published studies. Research design and methods: A systematic literature review was conducted to identify articles published in English over the last 10 years evaluating the use of OAHAs for the treatment of T2DM. Databases searched included PubMed/MEDLINE, EMBASE, and the Cochrane Library. Seventy studies reporting adherence, persistence or discontinuation were identified by two independent reviewers and 40 reported relevant endpoints for the analysis. Outcomes included: (1) mean adherence defined as the average medication possession ratio (MPR); (2) proportion of adherent patients (MPR ≥ 80%); (3) discontinuation; and (4) persistence. Adherence and persistence were reported in observational studies only. Discontinuation was examined separately in randomized controlled trials (RCTs) and observational studies. Meta-analyses were conducted using both fixed and random effects models. When meta-analysis was not appropriate for a given outcome, descriptive statistics were provided. Results: The pooled mean MPR (95% confidence interval [CI]) was 75.3% (68.8%–81.7%; n = 13) and the proportion of adherent patients (95% CI) was 67.9% (59.6%–76.3%; n = 12). The discontinuation rate (95% CI) in RCTs was 31.8% (17.0%–46.7%; n = 7). Persistence and discontinuation were not assessed via meta-analysis for observational studies due to the limited number of available studies and differences in outcome definitions. In these studies, persistence estimates ranged from 41.0% to 81.1%, with a mean (95% CI) of 56.2% (46.1%–66.3%; n = 6), while discontinuation estimates ranged from 9.9% to 60.1%, with a mean (95% CI) of 31.4% (17.6%–45.3%; n = 6). Limitations: Limitations include (1) the use of MPR as a proxy for adherence, (2) limited number of studies available, and (3) observed heterogeneity. Conclusion: The results of the analysis demonstrate that medication adherence, persistence, and discontinuation rates are suboptimal in patients with T2DM prescribed OAHAs.

Factors associated with adherence to oral antihyperglycemic monotherapy in patients with type 2 diabetes

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<0.05). Conclusion Patient characteristics, treatment regimens, and out-of-pocket expenses were associated with adherence to oral antihyperglycemic monotherapy in our study.

Risk characterization for urinary tract infections in subjects with newly diagnosed type 2 diabetes

AIM To evaluate the risk of urinary tract infections (UTI) in subjects with newly diagnosed type 2 diabetes mellitus (T2DM). METHODS Subjects aged ≥18years and diagnosed with T2DM between 1/1/10 and 12/31/10 were identified using the MarketScan® databases, which are representative of the commercially insured US population and those with both Medicare and supplemental coverage. The index date was the first T2DM diagnosis date in 2010 (date randomly selected for those without T2DM). Subjects without T2DM were matched (1:1) by index date, age, gender, urban/rural location, and region. All subjects had continuous enrollment for 12 months before (baseline) and after (follow-up) the index date. UTI diagnosis was defined using ICD-9-CM codes. Measurements of glycemic control and body weight were not available. An adjusted logistic regression model assessed the likelihood of UTI. RESULTS A total of 89,790 matched pairs were selected. During follow-up, a UTI diagnosis was more common in subjects with T2DM than without T2DM (9.4% vs. 5.7%; p<0.0001). Recurrence of UTI was also more likely with T2DM (1.6% vs. 0.6%; p<0.0001). In a logistic regression, subjects with T2DM had a greater likelihood of UTI during follow up (adjusted odds ratio [OR]=1.54 [95% CI: 1.47-1.60]). This relationship remained after stratifying by gender. CONCLUSION Subjects with T2DM were more likely to experience a UTI and recurrent UTIs than subjects without T2DM during follow-up.

Systematic Literature Review and Meta-analysis of Medication Adherence With Once-weekly Versus Once-daily Therapy.

PURPOSE To compare medication adherence rates for once-weekly (QW) versus once-daily (QD) dosing regimens in patients with chronic disease. METHODS A systematic literature review was conducted to identify articles published in English-language journals examining the rate of adherence to medications in patients with chronic disease. Relevant studies were identified from January 2002 through August 2013 using PubMed, EMBASE, and the Cochrane Library databases. Twenty-two published observational studies reporting adherence were identified by 2 independent reviewers, and 7 articles reported relevant measures for analysis. All studies were conducted in patients with osteoporosis. Meta-analyses estimated (1) mean difference (MD) in adherence (defined using the mean medication possession ratio [MPR]) between QW and QD dosing groups and (2) odds ratio (OR) for adherence (defined using an MPR cutoff of ≥80%) for QW versus QD dosing. Heterogeneity was assessed using Cochrans Q and I(2) values, and meta-analyses used both fixed- and random-effects models. FINDINGS The random-effects meta-analysis revealed a significantly greater MPR with QW compared with QD dosing (pooled MD = 12.29%; 95% CI, 10.76%-13.82%; n = 9 [data reported in 7 publications]). Because of the high level of heterogeneity (I(2) = 83.4%), the fixed-effects model results were not appropriate to report for the pooled MD. When examining the OR for adherence, both fixed- and random-effects models provided similar results due to the low level of heterogeneity (I(2) = 7.9%; n = 5 [data reported in 3 publications]). Using either model, the pooled odds of being adherent (MPR ≥80%) in the QW dosing group was approximately 1.9 times the odds in the QD dosing group (random-effects OR = 1.90; 95% CI, 1.81-2.00; fixed-effects OR = 1.92; 95% CI, 1.84-1.99). IMPLICATIONS In our meta-analysis, QW dosing was associated with better adherence levels and greater odds of being adherent compared with QD dosing in patients with osteoporosis.

Review of patient-reported outcome instruments measuring health-related quality of life and satisfaction in patients with type 2 diabetes treated with oral therapy.

Abstract Objective: Treatments and their mode of administration may represent a burden for patients and can therefore impact their health-related quality of life (HRQL) or treatment/health satisfaction. Patients with type 2 diabetes mellitus (T2DM) can be treated with oral hypoglycemic agents (OHAs), injectable medications (such as insulin), or a combination of agents. This review aimed to identify patient-reported outcome (PRO) instruments measuring HRQL and/or satisfaction that could differentiate between oral medications based on medication related attributes such as efficacy, tolerability, weight loss, dosing frequency and pill burden. Research design and Methods: Medline, Embase, PsycINFO, Cochrane Library and the Patient-Reported Outcome and Quality of Life Questionnaires (PROQOLID) biomedical databases were searched to identify instruments and document their development methodology, content and psychometric properties (i.e. validity, reliability), responsiveness and ability to detect changes between treatments. Results: Nineteen instruments were retained based on their potential to differentiate between OHAs. Ten instruments assessed HRQL, amongst which the Audit of Diabetes Dependent Quality of Life, Diabetes 39, Diabetes Health Profile and Impact of Weight on Quality of Life displayed good psychometric properties in T2DM populations and comprehensive HRQL content. Nine instruments assessed satisfaction. Both the Oral Hypoglycemic Agent Questionnaire (OHAQ) and Diabetes Medication Satisfaction (DiabMedSat) Questionnaire have highly relevant content regarding drug attributes. The OHAQ is specific to oral treatment and the DiabMedSat includes HRQL items. The Diabetes Treatment Satisfaction Questionnaire is a standard instrument that is extensively used and provides conclusive results in studies of patients with T2DM. Conclusions: Very few of the existing PRO instruments are specific to OHAs. Despite satisfaction instruments being recommended to differentiate between OHAs in studies of T2DM based on medication attributes, we find that none of the existing instruments appear to be useful in detecting differences between treatments, therefore limiting their use in clinical and observational research.

Assessing occurrence of hypoglycemia and its severity from electronic health records of patients with type 2 diabetes mellitus.

AIMS Accurate measures of hypoglycemia within electronic health records (EHR) can facilitate clinical population management and research. We quantify the occurrence of serious and mild-to-moderate hypoglycemia in a large EHR database in the US, comparing estimates based only on structured data to those from structured data and natural language processing (NLP) of clinical notes. METHODS This cohort study included patients with type 2 diabetes identified from January 2009 through March 2014. We compared estimates of occurrence of hypoglycemia derived from diagnostic codes to those recorded within clinical notes and classified via NLP. Measures of hypoglycemia from only structured data (ICD-9 Algorithm), only note mentions (NLP Algorithm), and either structured data or notes (Combined Algorithm) were compared with estimates of the period prevalence, incidence rate, and event rate of hypoglycemia, overall and by seriousness. RESULTS Of the 844,683 eligible patients, 119,695 had at least one recorded hypoglycemic event identified with ICD-9 or NLP. The period prevalence of hypoglycemia was 12.4%, 25.1%, and 32.2% for the ICD-9 Algorithm, NLP Algorithm, and Combined Algorithm, respectively. There were 6128 apparent non-serious events utilizing the ICD-9 Algorithm, which increased to 152,987 non-serious events within the Combined Algorithm. CONCLUSIONS Ascertainment of events from clinical notes more than doubled the completeness of hypoglycemia capture overall relative to measures from structured data, and increased capture of non-serious events more than 20-fold. The structured data and clinical notes are complementary within the EHR, and both need to be considered in order to fully assess the occurrence of hypoglycemia.

Hypoglycaemia seriousness and weight gain as determinants of cardiovascular disease outcomes among sulfonylurea users

Certain treatments for type 2 diabetes mellitus cause hypoglycaemia and weight gain, and thus might counteract the benefits of intensive glucose control. We quantify the association of cardiovascular disease (CVD) outcomes with hypoglycaemia and weight gain among patients with type 2 diabetes treated with sulfonylureas.

Risk factors associated with treatment discontinuation and down-titration in type 2 diabetes patients treated with sulfonylureas

Abstract Objectives: Sulfonylurea therapy among patients with type 2 diabetes mellitus (T2DM) can be disrupted due to adverse events, including hypoglycemia. A retrospective study using the MarketScan claims database quantified the frequency of sulfonylurea discontinuation or down-titration and identified associated risk factors. Research design and methods: Adult patients with an index sulfonylurea prescription between 2008 and 2012 and 1 year continuous enrollment pre- and post-index were included. Therapy changes assessed over 1 year post-index included discontinuation and down-titration. Discontinuation occurred if the date of a fill was >90 days from the end date of the preceding fill. Down-titration occurred when a fill had a lower equivalent dose than the fill on the index date. Kaplan–Meier methods estimated the probability of either discontinuation or down-titration over 12 months, and Cox regression models identified associated risk factors. Results: A total of 104,082 sulfonylurea users were included in the study and the probability of either discontinuation or down-titration at 3, 6 and 12 months was 23.2%, 38.9%, and 52.3%, respectively. Major risk factors associated with therapy changes included post-index hypoglycemia (discontinuation hazard ratio [HR] = 1.78 [1.68, 1.89]; down-titration HR =2.79 [2.40, 3.23]) and concomitant use of insulin (discontinuation HR =1.48 [1.40, 1.57]; down-titration HR =1.82 [1.56, 2.11]). Other risk factors included younger age, female gender, use of second generation sulfonylureas, prior cardiovascular comorbidity and liver disease. Limitations: The study was not able to assess unreported, potentially mild cases of hypoglycemia, nor was it able to evaluate the association between changes in therapy and HbA1c levels or body weight. Conclusions: More than half of T2DM patients who initiated sulfonylurea therapy discontinued or down-titrated within 1 year. Insulin use and hypoglycemia were associated with sulfonylurea therapy change.