Age-dependent prevalence of type 2 diabetes, cardiovascular risk profiles and use of diabetes drugs in Germany using health claims data.

AIMS: This study evaluates type 2 diabetes mellitus (T2DM) prevalence in Germany, focusing on patients at risk for, or with already established, cardiovascular disease (CVD), as well as their antidiabetic and cardiovascular treatments. MATERIALS AND METHODS: Using anonymized claims data from the WIG2 database, we calculated 2018 T2DM prevalence, extrapolating rates to the German statutory health insurance population. In the study period, 3 376 228 patients were eligible in the database. Forming antidiabetic medication groups, we evaluated treatment regimens of patients at risk for, or with already established CVD, based on the REWIND study criteria. We also evaluated their CVD medication prescriptions. RESULTS: Statutory health insurance extrapolated T2DM prevalence was estimated at 11.9%, with higher prevalence rates in older patients. When only patients with prescriptions of antidiabetic drugs were included, prevalence was 7.6%. At least 94% of patients with T2DM medication had at least one risk factor (without considering age) according to REWIND criteria, while 67%-80% had at least two risk factors depending on treatment received. Patients taking insulin combined with oral therapy comprised the largest proportion of patients with at least two REWIND risk factors. Approximately 85% of all patients with T2DM in the population were treated with antihypertensive medication. CONCLUSIONS: T2DM is widespread and affects older patients particularly. Most patients with T2DM had at least one CV risk factor, and about half already had established CVD. Early prevention of CVD, which disproportionately affects patients with T2DM, is necessary. Furthermore, the treatment of older patients with T2DM with insulin is still common and needs further evaluation.

Clinical characteristics, treatment patterns, and persistence in individuals with type 2 diabetes initiating a glucagon-like peptide-1 receptor agonist: A retrospective analysis of the Diabetes Prospective Follow-Up Registry.

AIMS: To describe clinical characteristics, treatment patterns and glucagon-like peptide-1 receptor agonist (GLP-1 RA) persistence in individuals with type 2 diabetes (T2D) initiating their first GLP-1 RA. MATERIALS AND METHODS: A real-world analysis of adults with T2D initiating GLP-1 RA therapy between 2007 and June 2020 from the multicentre Diabetes Prospective Follow-Up (DPV) Registry, stratified by antidiabetes therapy at the time of GLP-1 RA initiation: oral antidiabetic drugs (OAD), insulin ± OAD or lifestyle modification (LM). GLP-1 RA treatment persistence in individuals with ≥12 months follow-up was determined by Kaplan-Meier analysis. RESULTS: Overall, 15 111 individuals with T2D initiating GLP-1 RA therapy (55% men) were identified; median [interquartile range (IQR)] age [58.7 (50.6-66.7) years], diabetes duration [8.5 (3.6-14.7) years], glycated haemoglobin [HbA1c; 8.2 (7.1-9.8)%]. Median (95% confidence interval) GLP-1 RA persistence in eligible individuals (n = 5189) was 11 (10-12) months; OAD 12 (11-14) months (n = 2453); insulin ± OAD 11 (9-12) months (n = 2204); and LM 7 (5-9) months (n = 532). Median treatment persistence tended to increase from 2007-2012 to 2017-2020. Median (IQR) HbA1c decreased from baseline [8.2 (7.1-9.8)%] to discontinuation [7.5 (6.6-8.7)%], with a greater decrease observed in individuals with persistence >12 months versus ≤12 months. Individuals who discontinued GLP-1 RA therapy predominantly switched to insulin (if not already using) or dipeptidyl peptidase-4 inhibitors. CONCLUSION: Real-world registry data revealed improved outcomes with longer median GLP-1 RA persistence; ~50% of patients overall achieved HbA1c <7% at 12 months. Persistence was highest with baseline OAD and/or insulin, and tended to increase over the period 2007-2020.

The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients (TROPHIES): Final patient-reported outcomes at 24 months.

AIM: To report health-related patient-reported outcomes (PROs) in people with type 2 diabetes (T2D) initiating their first injectable glucose-lowering medication (GLM) with two commonly prescribed glucagon-like peptide-1 receptor agonists (GLP-1RAs) from the prospective, observational TROPHIES study (The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Type 2 Diabetes Patients). MATERIALS AND METHODS: TROPHIES was a two-cohort, 24-month study conducted in France, Germany and Italy. Adults with a T2D diagnosis, naïve to injectable treatment for T2D and prescribed dulaglutide or liraglutide as their first injectable GLM, were eligible for inclusion. Study objectives included describing the following PROs associated with the treatment of T2D with GLP-1RAs: health-related quality of life; impact of weight on self-perception; life and work productivity; and patient satisfaction with treatment and injection device. Additional analyses formally compared PRO measures between the treatment cohorts. RESULTS: Overall, improvements from baseline in PRO scores were observed among people who started dulaglutide or liraglutide. A more pronounced trend of improvement was observed in the dulaglutide cohort for changes from baseline in treatment satisfaction and impact of weight on self-perception, supported by statistically significant differences between treatment cohorts in additional comparative analyses at 12, 18 and 24 months. More positive patient perceptions of the injection device were observed with dulaglutide than with liraglutide. CONCLUSIONS: Improvements in PROs observed in TROPHIES, which were more evident with dulaglutide than liraglutide, reflect a relevant clinical benefit. From the patients' perspective, satisfaction, and confidence in continuing treatment with GLP-1RAs is likely to contribute to long-term treatment persistence.

The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes (TROPHIES): Final, 24-month analysis of time to first significant treatment change, treatment persistence and clinical outcomes.

AIMS: To present the final results of the TROPHIES study (The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in patients with type 2 diabetes). MATERIALS AND METHODS: The prospective, real-world TROPHIES study included patients with type 2 diabetes initiating their first injectable glucose-lowering medication (GLM), dulaglutide or liraglutide, in France, Germany and Italy. The primary endpoint was the time spent on dulaglutide or liraglutide until a significant treatment change over 24 months. Other endpoints measured persistence with treatment, clinical outcomes (glycated haemoglobin [HbA1c] and weight) and treatment patterns. Kaplan-Meier estimates of time to first significant treatment change and persistence with treatment were generated. Propensity-score-based inverse probability of treatment weighting (IPTW) was used to adjust for baseline imbalances in the comparison between cohorts. RESULTS: The 286 of 1014 patients (28.2%) in the dulaglutide cohort and 448 of 991 patients (45.2%) in the liraglutide cohort had a significant treatment change over 24 months. By IPTW analysis, dulaglutide-initiating patients were less likely to have a significant treatment change (hazard ratio [HR] 0.54, 95% confidence interval [CI] 0.46-0.63) and more likely to be persistent with treatment (HR 0.69, 95% CI 0.56-0.86) over 24 months than liraglutide-initiating patients. Dulaglutide and liraglutide yielded similar HbA1c (-11.80 mmol/mol [1.08%] and -11.91 mmol/mol [1.09%]) and weight (-3.5 kg and -3.3 kg) reductions from baseline to 24 months. Few changes in patterns of treatment with other GLMs were observed in the two cohorts. CONCLUSIONS: Dulaglutide-initiating patients had a longer time spent without any significant treatment change and higher persistence than those initiating liraglutide. Treatment with either glucagon-like peptide-1 receptor agonist yielded similar and clinically meaningful reductions in HbA1c and body weight.

The Real-World Observational Prospective Study of Health Outcomes with Dulaglutide and Liraglutide in Patients with Type 2 Diabetes (TROPHIES): Patient disposition, clinical characteristics and treatment persistence at 12 months.

AIMS: The primary objective of the TROPHIES observational study is to estimate the duration of treatment on dulaglutide or liraglutide without a significant treatment change by 24 months in patients with type 2 diabetes (T2D) initiating their first injectable treatment with these glucagon-like peptide-1 receptor agonists (GLP-1 RAs). This manuscript presents 12-month interim data. MATERIALS AND METHODS: TROPHIES is a prospective, non-comparative, observational study of patients with T2D in Europe, naïve to injectable antihyperglycaemic treatments and initiating dulaglutide or liraglutide. Data on clinical characteristics, GLP-1 RA persistence and treatment patterns of glucose-lowering medication were collected at initiation of first injectable therapy and by 12 months. RESULTS: By 12 months, 1014 dulaglutide and 991 liraglutide patients were eligible across France, Germany and Italy. Both cohorts presented a high probability [95% confidence interval (CI)] of GLP-1 RA persistence [dulaglutide, 0.88 (0.86 to 0.90); liraglutide, 0.83 (0.80 to 0.85)] and reduction in mean glycated haemoglobin percentage (95% CI) from baseline [dulaglutide, -1.18 (-1.27 to -1.08); liraglutide, -1.15 (-1.26 to -1.05)] with 48.2% of dulaglutide and 41.2% of liraglutide patients reaching their individualized glycated haemoglobin percentage target set by the physician at baseline. Mean weight (95% CI) change from baseline was -3.2 kg (-3.6 to -2.8) for dulaglutide and -3.4 kg (-3.9 to -3.0) for liraglutide. Slight changes in concomitant medications were observed compared with baseline. CONCLUSIONS: In the real-world setting, dulaglutide and liraglutide cohorts achieved good persistence with similarly improved glycaemic control that was accompanied by weight loss at 12 months, consistent with previous clinical trial results.

Treatment persistence in patients with type 2 diabetes treated with glucagon-like peptide-1 receptor agonists in clinical practice in Sweden.

AIM: To compare treatment persistence in patients with type 2 diabetes initiating the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) dulaglutide, exenatide once-weekly (QW), liraglutide or lixisenatide in routine clinical practice in Sweden and assess clinical outcomes. MATERIALS AND METHODS: We performed a retrospective study using data from several nationwide Swedish health registries, including the National Diabetes Register and other mandatory and population-based registries. Individual level data were collected from 17 361 patients who initiated GLP-1 RA treatment from 23 May 2015 to 15 October 2017, up to 2.5 years postindex (treatment start date). Treatment persistence and modification, predictors of discontinuation, HbA1c and body weight were recorded. Non-persistence was defined as a treatment gap of more than 45 days. Treatment modification included switching and augmentation. Confounding was addressed through the use of propensity scores. RESULTS: Treatment persistence was higher and treatment modifications were lower in patients initiating dulaglutide compared with those on exenatide QW, liraglutide and lixisenatide. Patients who remained on the same treatment for 1-year postindex experienced greater HbA1c reductions and a steadier decrease in body weight. CONCLUSIONS: Our study suggests that in clinical practice in Sweden there is a greater persistence of treatment among patients initiating dulaglutide compared with those on exenatide QW, liraglutide and lixisenatide. Persistence with the index GLP-1 RA was closely correlated with positive clinical outcomes and thus should be considered a critical factor of patient-centric treatment in Sweden.

Dulaglutide treatment results in effective glycaemic control in latent autoimmune diabetes in adults (LADA): A post-hoc analysis of the AWARD-2, -4 and -5 Trials.

AIMS: Patients with a type-2-diabetes (T2D) phenotype positive for glutamic acid decarboxylase antibodies (GADA) represent the majority of cases of latent autoimmune diabetes of the adult (LADA). The GLP-1 receptor agonist dulaglutide, recently introduced for treatment of T2D, has yet to be evaluated in LADA patients. Our primary objective was to evaluate the effect of dulaglutide on glycaemic control (HbA1c) in GADA-positive LADA vs GADA-negative T2D patients. METHODS: A post-hoc analysis was performed using data from 3 randomized phase 3 trials (AWARD-2,-4,-5; patients with GADA assessment) which were part of the dulaglutide clinical development programme in T2D. LADA patients were identified by GADA ≥5 IU/mL (ELISA). Changes in HbA1c during 12 months of treatment with dulaglutide or comparator were analysed using mixed-effect model repeated measures. RESULTS: Of 2466 adults tested for GADA (dulaglutide, 1710; glargine, 298; sitagliptin, 294; placebo, 164), 2278 (92.4%) were GADA-negative and 188 (7.6%) were GADA-positive, including 58 GADA-high patients (> 200 IU/mL) and 130 GADA-low patients (≤200 and ≥5 IU/mL). Overall, baseline parameters were comparable between the groups. Dulaglutide resulted in comparable HbA1c reductions in GADA-negative (LS mean change [95%CI], -1.09% [-1.15, -1.03]) and GADA-positive patients (-0.94% [-1.15, -0.72]) at 12 months. HbA1c reductions were numerically, but not statistically, significantly larger in GADA-low patients (-1.02% [-1.26, -0.78]) vs GADA-high patients (-0.72% [-1.21,-0.24]) at 12 months. Similar outcomes were observed at 3 and 6 months. CONCLUSIONS: These data are the first to indicate that dulaglutide was effective in reducing HbA1c in LADA patients.

Potential cost savings to be made by slowing cognitive decline in mild Alzheimer's disease dementia using a model derived from the UK GERAS observational study.

BACKGROUND: Given the high costs associated with the care of those with Alzheimer's disease (AD) dementia, we examined the likely impact of a reduction in the rate of cognitive decline upon cost outcomes associated with this disease. METHODS: Using the group of patients with mild AD dementia from the GERAS study, generalised linear modelling (GLM) was used to explore the relationship between change in cognition as measured using the Mini-Mental State Examination (MMSE) and UK overall costs (health care and social care costs, and total societal costs) associated with AD dementia. RESULTS: A total of 200 patients with mild AD dementia were identified. Least squares mean (LSM) ± standard error (SE) reduction in MMSE score was 3.6 ± 0.4 points over 18 months. Using GLM it was possible to calculate that this worsening in cognition was associated with an 8.7% increase in total societal costs, equating to an increase of approximately £2200 per patient over an 18-month period. If the rate of decline in cognition was reduced by 30% or 50%, the associated savings in total societal costs over 18 months would be approximately £670 and £1100, respectively, of which only £110 and £180, respectively, could be attributed to a saving of health care costs. CONCLUSION: This study demonstrates that there are potential savings to be made in the care of patients with AD dementia through reducing the rate of cognitive decline. A reduction in wider societal costs is likely to be the main contributor to these potential savings, and need to be further evaluated when intervention costs and cost offsets can be measured.

How useful is the EQ-5D in assessing the impact of caring for people with Alzheimer's disease?

BACKGROUND: The impact on informal caregivers of caring for people with Alzheimer's disease (AD) dementia can be substantial, but it remains unclear which measures(s) best assess such impact. Our objective was to use data from the GERAS study to assess the ability of the EuroQol 5-dimension questionnaire (EQ-5D) to measure the impact on caregivers of caring for people with AD dementia and to examine correlations between EQ-5D and caregiver burden. METHODS: GERAS was a prospective, non-interventional cohort study in community-dwelling patients with AD dementia and their informal caregivers. The EQ-5D and Zarit Burden Interview (ZBI) were used to measure health-related quality of life and caregiver burden, respectively. Resource-use data collected included caregiver time spent with the patient on activities of daily living (ADL). Spearman correlations were computed between EQ-5D scores, ZBI scores, and time spent on instrumental ADL (T-IADL) at baseline, 18 months, and for 18-month change scores. T-IADL and ZBI change scores were summarized by EQ-5D domain change category (better/stable/worse). RESULTS: At baseline, 1495 caregivers had mean EQ-5D index scores of 0.86, 0.85, and 0.82, and ZBI total scores of 24.6, 29.4, and 34.1 for patients with mild, moderate, and moderately severe/severe AD dementia, respectively. Change in T-IADL showed a stronger correlation with change in ZBI (0.12; P < 0.001) than with change in EQ-5D index score (0.02; P = 0.546) although both correlations were very weak. Worsening within EQ-5D domains was associated with increases in ZBI scores, although 68%-90% of caregivers remained stable within each EQ-5D domain. There was no clear pattern for change in T-IADL by change in EQ-5D domain. CONCLUSIONS: EQ-5D may not be the optimum measure of the impact of caring for people with AD dementia due to its focus on physical health. Alternative measures need further investigation.

Broader conceptualization of remission assessed by the remission from depression questionnaire and its association with symptomatic remission: a prospective, multicenter, observational study.

BACKGROUND: Goals of treating major depressive disorder (MDD) include achieving remission and avoiding relapse. It is possible that patients may have a broader view of remission than what is captured via clinician-rated scales. This patient perspective may, in turn, have an impact on treatment outcomes. METHODS: The association between a broader conceptualization of remission, based on the Remission from Depression Questionnaire (RDQ) score at baseline, and being in symptomatic remission after 6 months was evaluated in subjects (N = 613) with MDD in symptomatic remission at baseline (17-item Hamilton Rating Scale for Depression [HAMD-17] ≤7). Specific aspects of depression were assessed from physician and patient perspectives as secondary endpoints. A backwards selection strategy was used to statistically model remission status and determine association of factors with potential to influence remission. RESULTS: At month 6, after adjustment for baseline HAMD-17 score, there was no association between baseline RDQ score and symptomatic remission status (HAMD-17), relapse, composite remission status, healthcare resource utilization, or quality of life. There was no association between functional impairment scores at baseline (Sheehan Disability Scale and Social and Occupational Functioning Assessment Scale) and symptomatic remission status (HAMD-17) at month 6. CONCLUSIONS: This study indicates that RDQ-constructs are independent from symptomatic remission. Symptom severity at study entry appeared to be the only significant predictor of eventual relapse during the 6-month follow-up period. However, our results also suggest that the current definition of remission that is based on symptom reduction should be further elaborated and that alternative or additional definitions should be considered in determining remission.

Resource utilisation, costs and clinical outcomes in non-institutionalised patients with Alzheimer's disease: 18-month UK results from the GERAS observational study.

BACKGROUND: Alzheimer's disease (AD), the commonest cause of dementia, represents a significant cost to UK society. This analysis describes resource utilisation, costs and clinical outcomes in non-institutionalised patients with AD in the UK. METHODS: The GERAS prospective observational study assessed societal costs associated with AD for patients and caregivers over 18 months, stratified according to baseline disease severity (mild, moderate, or moderately severe/severe [MS/S]). All patients enrolled had an informal caregiver willing to participate in the study. Healthcare resource utilisation was measured using the Resource Utilization in Dementia instrument, and 18-month costs estimated by applying unit costs of services and products (2010 values). Total societal costs were calculated using an opportunity cost approach. RESULTS: Overall, 526 patients (200 mild, 180 moderate and 146 MS/S at baseline) were recruited from 24 UK centres. Mini-Mental State Examination (MMSE) scores deteriorated most markedly in the MS/S patient group, with declines of 3.6 points in the mild group, 3.5 points in the moderate group and 4.7 points in the MS/S group; between-group differences did not reach statistical significance. Patients with MS/S AD dementia at baseline were more likely to be institutionalised (Kaplan-Meier probability 28% versus 9% in patients with mild AD dementia; p < 0.001 for difference across all severities) and had a greater probability of death (Kaplan-Meier probability 15% versus 5%; p = 0.013) at 18 months. Greater disease severity at baseline was also associated with concomitant increases in caregiver time and mean total societal costs. Total societal costs of £43,560 over 18 months were estimated for the MS/S group, versus £25,865 for the mild group and £30,905 for the moderate group (p < 0.001). Of these costs, over 50% were related to informal caregiver costs at each AD dementia severity level. CONCLUSIONS: This study demonstrated a mean deterioration in MMSE score over 18 months in patients with AD. It also showed that AD is a costly disease, with costs increasing with disease severity, even when managed in the community: informal caregiver costs represented the main contributor to societal costs.

Effect of diabetes on caregiver burden in an observational study of individuals with Alzheimer's disease.

BACKGROUND: The burden on caregivers of patients with Alzheimer's disease (AD) is associated with the patient's functional status and may also be influenced by chronic comorbid medical conditions, such as diabetes. This post-hoc exploratory analysis assessed whether comorbid diabetes in patients with AD affects caregiver burden, and whether caregivers with diabetes experience greater burden than caregivers without diabetes. Caregiver and patient healthcare resource use (HCRU) were also assessed. METHODS: Baseline data from the GERAS observational study of patients with AD and their caregivers (both n = 1495) in France, Germany and the UK were analyzed. Caregiver burden was assessed using the Zarit Burden Interview (ZBI). Caregiver time on activities of daily living (ADL: basic ADL; instrumental ADL, iADL) and supervision (hours/month), and caregiver and patient HCRU (outpatient visits, emergency room visits, nights hospitalized) were assessed using the Resource Utilization in Dementia instrument for the month before the baseline visit. Regression analyses were adjusted for relevant covariates. Time on supervision and basic ADL was analyzed using zero-inflated negative binomial regression. RESULTS: Caregivers of patients with diabetes (n = 188) were younger and more likely to be female (both p < 0.05), compared with caregivers of patients without diabetes (n = 1307). Analyses showed caregivers of patients with diabetes spent significantly more time on iADL (+16 %; p = 0.03; increases were also observed for basic ADL and total caregiver time but did not reach statistical significance) and had a trend towards increased ZBI score. Patients with diabetes had a 63 % increase in the odds of requiring supervision versus those without diabetes (p = 0.01). Caregiver and patient HCRU did not differ according to patient diabetes. Caregivers with diabetes (n = 127) did not differ from those without diabetes (n = 1367) regarding burden/time, but caregivers with diabetes had a 91 % increase in the odds of having outpatient visits (p = 0.01). CONCLUSIONS: This cross-sectional analysis found caregiver time on iADL and supervision was higher for caregivers of patients with AD and diabetes versus without diabetes, while HCRU was unaffected by patient diabetes. Longitudinal analyses assessing change in caregiver burden over time by patient diabetes status may help clarify the cumulative impact of diabetes and AD dementia on caregiver burden.

Prevalence of ADHD in nonpsychotic adult psychiatric care (ADPSYC): A multinational cross-sectional study in Europe.

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. This study was designed to estimate the prevalence of ADHD in adult psychiatric outpatients in several European countries. METHOD: ADHD diagnosis was made using the Diagnostic Interview for ADHD in Adults, version 2.0 (DIVA), according to criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR) and 5th Edition (DSM-5). RESULTS: Of 5662 patients present/approached, 2284 (40.3 %) consented, of whom 1986 patients (87.0 %) completed the study. Based on the DIVA, and applying DSM-IV-TR or DSM-5 criteria, 15.8 % (95 % confidence interval [CI] 14.2 %-17.4 %) or 17.4 % (95 % CI 15.7 %-19.0 %) of patients were diagnosed with ADHD, respectively. The prevalence of ADHD was 15.3 % when counting as non-ADHD those patients who screened positive but did not complete the DIVA (DSM-5). CONCLUSIONS: Estimates from this study indicate that a relevant part of the psychiatric outpatient care population suffers from ADHD.

The real-world observational prospective study of health outcomes with dulaglutide and liraglutide in type 2 diabetes patients (TROPHIES): resource use and costs of treatment in clinical practice in France, Germany, and Italy.

AIMS: To describe healthcare resource utilization (HCRU) and associated costs after initiation of injectable glucagon-like peptide-1 receptor agonist (GLP-1 RA) therapy by adult patients with type 2 diabetes (T2D) in the prospective, observational, 24-month TROPHIES study in France, Germany, and Italy. MATERIALS AND METHODS: HCRU data for cost calculations were collected by treating physicians during patient interviews at baseline and follow-up visits approximately 6, 12, 18, and 24 months after GLP-1 RA initiation with once-weekly dulaglutide or once-daily liraglutide. Costs were evaluated from the national healthcare system (third-party payer) perspective and updated to 2018 prices. RESULTS: In total, 2,005 patients were eligible for the HCRU analysis (1,014 dulaglutide; 991 liraglutide). Baseline patient characteristics were generally similar between treatment groups and countries. The largest proportions of patients using ≥2 oral glucose-lowering medications (GLMs) at baseline (42.9-43.4%) and month 24 (44.0-45.1%) and using another injectable GLM at month 24 (15.3-23.2%) were in France. Mean numbers of primary and secondary healthcare contacts during each assessment period were highest in France (range = 4.0-10.7) and Germany (range = 2.9-5.7), respectively. The greatest proportions (≥60%) of mean annualized costs per patient comprised medication costs. Mean annualized HCRU costs per patient varied by treatment cohort and country: the highest levels were in the liraglutide cohort in France (€909) and the dulaglutide cohort in Germany (€883). LIMITATIONS: Limitations included exclusion of patients using insulin at GLP-1 RA initiation and collection of HCRU data by physician, not via patient-completed diaries. CONCLUSIONS: Real-world HCRU and costs associated with the treatment of adults with T2D with two GLP-1 RAs in TROPHIES emphasize the need to avoid generalization with respect to HCRU and costs associated with a particular therapy when estimating the impact of a new treatment in a country-specific setting.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have become frequent treatments of hyperglycemia in type-2 diabetes (T2D). Not all types of clinical study provide information about the cost of these treatments or the effects they might have on use of other medicines and equipment to control T2D or the need for visits to a doctor or nurse and different types of treatment in hospital. This study collected this information during the regular care of adults in France, Germany, or Italy who were prescribed either dulaglutide or liraglutide (both types of GLP-1 RAs) by their family doctor or a specialist in T2D. There were differences in costs and the need for other medicines and medical services between people using either dulaglutide or liraglutide and for people who were using the same GLP-1 RA in each of the three countries. The information from this study could be used to more accurately understand the overall costs and medical care needed when patients use dulaglutide or liraglutide in France, Germany, or Italy.

Dealing with heterogeneity between cohorts in genomewide SNP association studies.

In Genomewide association (GWA) studies investigating thousands of SNPs, large sample sizes are needed to obtain a reasonable power after correction for multiple testing. To obtain the necessary sample sizes, data from different populations/cohorts are combined. The problem of pooling evidence across cohorts bears some resemblance with meta-analysis of clinical trials, and in fact classical meta-analytic methodologies from that field are typically used in GWAs. However, in genetics, it can be expected that the cohorts show some amount of heterogeneity in the association measures that are used for significance testing. In this paper, we demonstrate how it is possible to exploit this heterogeneity to improve our ability to detect influential genetic variants. We also discuss how pathway analysis based on summary data can help resolve heterogeneity. The current standard method for testing SNPs across cohorts in GWAs will miss heterogeneous but important genetic variants affecting complex diseases. Our new testing strategy has the potential to detect them while maintaining sensitivity to variants with homogeneous effects.

Glucagon-Like Peptide 1 Receptor Agonists in Type 2 Diabetes Mellitus: Data from a Real-World Study in Spain.

INTRODUCTION: This study aimed to describe utilization patterns, persistence, resource utilization and costs in patients with type 2 diabetes mellitus initiating treatment with glucagon-like peptide 1 receptor agonists in routine clinical practice in Spain. METHODS: This retrospective study of medical records in the Big-Pac database identified adults starting treatment with once-weekly (QW) dulaglutide, exenatide-QW or once-daily liraglutide between 1 November 2015 and 30 June 2017. Patients were followed for up to 18 months from treatment initiation. Data on clinical characteristics of patients, treatment patterns, average daily dose and costs were obtained for the three cohorts. Persistence over the 18-month period was evaluated using Kaplan-Meier curves. All analyses were descriptive. RESULTS: A total of 1402 patients were included in this study (dulaglutide [n = 492], exenatide-QW [n = 438] or liraglutide [n = 472]); 52.8% were men, and the mean (SD) age was 62 (11) years, glycated haemoglobin (HbA1c) was 8.1% (1.2) and body mass index was 35.5 (3.2) kg/m2 at treatment initiation. Persistence at 18 months was 59.1% (95% confidence interval [CI] 54.8-63.4) for dulaglutide, 45.7% (95% CI 41.0-50.4) for exenatide-QW and 46.6% (95% CI 42.1-51.1) for liraglutide. The average (SD) dose was 1.2 (0.4) mg/week for dulaglutide, 1.9 (0.3) mg/week for exenatide-QW and 1.1 (0.3) mg/day for liraglutide. The average reduction in HbA1c levels at 1 year was - 0.68% for patients who initiated dulaglutide, - 0.54% for patients who initiated exenatide-QW and - 0.50% for patients who initiated liraglutide. The mean (SD) total annual health care costs were €4072 (1946) for dulaglutide, €4418 (2382) for exenatide-QW and €4382 (2389) for liraglutide. CONCLUSION: Results suggest that patients who started treatment with dulaglutide had higher persistence over 18 months, presented lower HbA1c levels at 12 months and incurred lower annual total healthcare costs than patients who initiated exenatide-QW or liraglutide.

Type 2 diabetes has a major impact on patients psychologically and socially, as well as on healthcare costs. The glucagon-like peptide 1 receptor agonists (GLP-1 RAs) are drugs that help maintain blood sugar at healthy levels. They are often used as the first injectable drugs if oral treatments are no longer effective. This study aimed to analyse the use of GLP-1 RAs, and the costs involved, among patients with type 2 diabetes who started treatment with once-weekly dulaglutide, once-weekly exenatide or liraglutide in routine clinical practice in Spain. An electronic database of medical records was used to obtain data from 1402 patients who started treatment with these drugs and were followed for a 1.5-year period. Results of this study suggest that patients who were prescribed dulaglutide stayed on their treatment longer and could reduce their blood sugar levels more efficiently, and at a lower cost, than those who received once-weekly exenatide or liraglutide. These findings could be helpful to physicians prescribing these drugs when considering how to improve the management of type 2 diabetes.

Treatment Patterns and Persistence With GLP-1 RA Treatments Among Patients With Type 2 Diabetes in France: A Retrospective Cohort Analysis.

INTRODUCTION: In type 2 diabetes (T2D), persistence with injectable glucose-lowering therapy is associated with better outcomes. This study used real-world pharmacy data to report on persistence with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D in France. METHODS: This retrospective cohort analysis presents longitudinal data from approximately 7500 French retail pharmacies that filled GLP-1-RA prescriptions for GLP-1 RA-naïve patients with T2D ('index therapy': dulaglutide; once-weekly exenatide [exenatide QW]; twice-daily exenatide [exenatide BID]; liraglutide) between January 2015 and December 2016 (follow-up ≥ 12 months). The main outcome was treatment persistence (absence of discontinuation [gap following index therapy prescription ≥ 2-fold the expected duration of that prescription] or switch [new non-index glucose-lowering prescription issued ≤ 30 days before/after index therapy discontinuation]). Persistence was calculated as the median duration through Kaplan-Meier survival analysis over the variable follow-up period and as the proportion of patients persistent at 12 months. In addition to persistence outcomes (discontinuation/switch), three other treatment modifications were assessed: augmentation/intensification with a new non-index glucose-lowering therapy; off-label dose increase (daily dose > 20 µg for exenatide BID; two consecutive prescriptions with daily dose > 1.8 mg for liraglutide); and off-label dose decrease (two consecutive prescriptions with average daily dose lower than the index dose). Off-label dose changes were not assessed for dulaglutide or exenatide QW (as single-dose, prefilled pens). RESULTS: Median persistence was longest for dulaglutide (373 days) versus liraglutide (205 days), exenatide QW (184 days) and exenatide BID (93 days). Twelve months after treatment initiation, the percentage of persistent patients ranged from 51% (dulaglutide) to 21% (exenatide BID). Overall, treatment modification occurred less commonly for dulaglutide than for the other index GLP-1 RAs. CONCLUSION: This analysis revealed marked differences in persistence among GLP-1 RAs, which was highest for dulaglutide and lowest for exenatide BID. The prospective TROPHIES study will provide additional information about persistence with dulaglutide and liraglutide, including reasons for treatment modifications.

Patients with type 2 diabetes (T2D) who continue to take injectable glucose-lowering therapy for the duration of time recommended by their physician (i.e. those who are 'persistent') usually have better outcomes than those who do not. Persistence may be quantified as the "the duration of time from initiation to discontinuation of therapy". Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are glucose-lowering agents that are often used as the first injectable drug if oral treatments are no longer effective. The aim of the current study was to use data from approximately 7500 retail pharmacies to report persistence with each of four GLP-1 RAs (dulaglutide, once-weekly exenatide [exenatide QW], twice-daily exenatide [exenatide BID] or liraglutide) in GLP-1 RA-naïve patients with T2D in France. Patients (N = 15,074) initiated treatment between January 2015 and December 2016 and were followed for ≥ 12 months. The total duration of follow-up varied among patients. Among patients, persistence over the variable follow-up period was highest for dulaglutide and lowest for exenatide BID: median persistence was longer for dulaglutide (373 days) than for liraglutide (205 days), exenatide QW (184 days) or exenatide BID (93 days). Twelve months after treatment initiation, the percentage of persistent patients ranged from 51% (dulaglutide) to 21% (exenatide BID), with intermediate values for exenatide QW (35%) and liraglutide (36%). This analysis has revealed marked differences in the persistence of patients for various GLP-1 RAs, with patients on dulaglutide showing the highest persistence and those on exenatide BID the lowest.

Real-World Use of Insulin Glargine U100 and U300 in Insulin-Naïve Patients with Type 2 Diabetes Mellitus: DosInGlar Study.

INTRODUCTION: In the EDITION clinical trial programme, patients with type 2 diabetes mellitus (T2DM) receiving insulin glargine (IGlar) U300 required 10-15% more insulin than those receiving IGlar U100. This study sought to determine whether this difference was apparent in real-world practice. METHODS: In this observational, retrospective cohort study, electronic medical records in the Big-Pac® database (Real Life Data) relating to adult insulin-naïve patients with T2DM who initiated IGlar U100 or U300 treatment in Spain in 2016-2017 and remained on treatment for 18 months were selected. IGlar U100- and U300-treated patients were matched 1:1 (propensity score matching). The primary analysis compared changes from baseline in mean daily IGlar dose (U and U/kg) at 6 (± 2), 12 (± 2) and 18 (± 2) months between cohorts (paired t tests). Changes in glycated haemoglobin (HbA1c) and weight were analysed descriptively. RESULTS: The IGlar U100 and U300 cohorts included 556 matched pairs (46.9% female) with the following mean (standard deviation) values at baseline, respectively: age 63.6 (12.8) versus 63.7 (11.9) years; years since diagnosis 9.5 (1.4) versus 9.5 (1.3); HbA1c 8.8 (1.3) versus 8.7 (1.5) %; weight 84.6 (16.9) versus 84.7 (17.1) kg. Mean IGlar dose at baseline was 0.19 U/kg/day (both cohorts). Patients receiving IGlar U300 showed a greater increase from baseline in IGlar dose at 6, 12 and 18 months [mean dose (U/kg/day) 5.1%, 10.3% and 12.8% greater, respectively, in IGlar U300-treated patients]. Mean HbA1c was 8.1% in both cohorts at 18 months. Mean (SD) weight at 18 months with IGlar U100 and IGlar300 was 86.8 (17.0) kg and 85.0 (17.1) kg, respectively. CONCLUSION: In real-world practice, insulin dose was significantly higher in IGlar U300-treated than U100-treated patients at 6, 12 and 18 months, with similar reductions in HbA1c. At equal IGlar price/unit in Spain, the increased dose requirements of IGlar U300 would result in higher costs.

Inclusion of a priori information in genome-wide association analysis.

Genome-wide association studies (GWAS) continue to gain in popularity. To utilize the wealth of data created more effectively, a variety of methods have recently been proposed to include a priori information (e.g., biologically interpretable sets of genes, candidate gene information, or gene expression) in GWAS analysis. Six contributions to Genetic Analysis Workshop 16 Group 11 applied novel or recently proposed methods to GWAS of rheumatoid arthritis and heart disease related phenotypes. The results of these analyses were a variety of novel candidate genes and sets of genes, in addition to the validation of well-known genotype-phenotype associations. However, because many methods are relatively new, they would benefit from further methodological research to ensure that they maintain type I error rates while increasing power to find additional associations. When methods have been adapted from other study types (e.g., gene expression data analysis or linkage analysis), the lessons learned there should be used to guide implementation of techniques. Lastly, many open research questions exist concerning the logistic details of the origin of the a priori information and the way to incorporate it. Overall, our group has demonstrated a strong potential for identifying novel genotype-phenotype relationships by including a priori data in the analysis of GWAS, while also uncovering a series of questions requiring further research.