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.

Estimating meaningful change for The Impact of Weight on Self-Perception (IW-SP) questionnaire among people with type 2 diabetes.

PURPOSE: The Impact of Weight on Self-perception Questionnaire (IW-SP) is a three-item patient-reported outcome measure (PROM) instrument assessing the impact of body weight on self-perception. To date no published threshold for meaningful change exists. The objective of this study was to estimate the minimal important change (MIC) for the IW-SP among people with type 2 diabetes. METHODS: Responder analyses were conducted using anchor- and distribution-based approaches with existing clinical trial data (SURPASS-2). As SURPASS-2 did not include a priori anchors, a set of alternative exploratory anchors were identified based on the MICs and items from two conceptually related measures used in the trial as well as percent change in body weight. Exploratory anchors with change estimates that were sufficiently related to change in IW-SP (r ≥ 0.30) and were not redundant with other anchors were retained for the MIC analyses. The analyses were conducted in two stages (estimation = 2/3 of sample) to derive initial IW-SP MIC estimates, and a subsequent confirmation stage (remaining 1/3 of sample). RESULTS: While the most conceptually related anchors and items performed best in responsiveness analyses, all anchors resulted in a similar estimate of minimal meaningful change for the IW-SP total score: a 1-point change in raw units (1-5-point scale), corresponding to a 25-point change for transformed scores (0-100 scale). Distribution-based analyses supported these MIC estimates. Results were similar across both stages for all analyses. CONCLUSION: The MIC for the IW-SP for patients with T2D is a 25-point change on the transformed score.

Efficacy and Safety of Tirzepatide in Adults With Type 2 Diabetes: A Perspective for Primary Care Providers.

This article reviews the efficacy and safety data of tirzepatide, a once-weekly, novel glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 (GLP-1) receptor agonist approved in the United States, the European Union, and other regions for the treatment of type 2 diabetes. All doses of tirzepatide demonstrated superiority in reducing A1C and body weight from baseline versus placebo or active comparators. The safety profile of tirzepatide was consistent with that of the GLP-1 receptor agonist class, with mild to moderate and transient gastrointestinal side effects being the most common adverse events. With clinically and statistically significant reductions in A1C and body weight without increased risk of hypoglycemia in various populations, tirzepatide has demonstrated potential as a first-in-class treatment option for many people with type 2 diabetes.

Type 2 diabetes pharmacotherapy trends in high-risk subgroups.

Medication use trends among patients with type 2 diabetes from 2015 to 2019 were investigated in relation to the clinical group-specific recommendations from the 2018 American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD) consensus report. Data were drawn from a large health insurance claims database representing Commercial (total patient-year count: 2,379,704) and Medicare (total patient-year count: 845,823) insurance programmes (IBM® MarketScan®). The utilization of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists increased over time but was lower in the Medicare cohort in every year evaluated. Patients diagnosed with obesity received recommended therapies at higher rates than those without obesity. Differences were more modest between those with versus without atherosclerotic cardiovascular disease (ASCVD) or chronic kidney disease, with greater treatment adoption in those without ASCVD in the Medicare cohort. Utilization of recommended treatments was paradoxically lower in those with versus without heart failure, and worse in the Medicare than in the Commercial cohort. Utilization of sulphonylureas was not different in those with versus without severe hypoglycaemia history. In conclusion, utilization of therapies recommended in the guidelines is increasing overall, which is not preferentially guided by ADA/EASD-defined clinical groups, and there exists a persistent gap in utilization between Commercial and Medicare populations.

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.

Patients' preferences for once-daily oral versus once-weekly injectable diabetes medications: The REVISE study.

AIMS: To understand patient preferences for once-daily oral versus once-weekly injectable type 2 diabetes mellitus (T2DM) medication administration profiles, and reasons for their preferences. MATERIALS AND METHODS: The REVISE study, a cross-sectional online survey of 600 participants with T2DM (United Kingdom, n = 300; United States, n = 300), elicited general preferences for once-daily oral versus once-weekly injectable diabetes medications, and reasons for the preference. Participants then viewed two videos describing the administration procedures for injectable dulaglutide and oral semaglutide, based on the product instructions for use. Thereafter, participants indicated their preference for a once-weekly injectable or a once-daily oral medication based on the video descriptions. Participants who switched preferences were asked to identify the reasons influencing their decision. RESULTS: The participants were predominantly male (n = 349; 58.2%), with a mean (SD) age of 64 (11.3) years. Nearly all (n = 557; 92.8%) were taking an oral T2DM medication, and 158 (26.3%) were using an injectable. Initially, 76.5% (n = 459; 95% confidence interval [CI] 73.1-79.9) preferred a once-daily oral and 23.5% a once-weekly injectable (n = 141; 95% CI 20.1-26.9; P < 0.0001). After viewing the videos describing the product-specific administration, the proportions of participants preferring each option were not statistically different (oral semaglutide administration description (n = 315; 52.5%; 95% CI 48.5-56.5; dulaglutide administration description (n = 285; 47.5%; 95% CI 43.5-51.5; NS, P = 0.2207). The most common reason for switching preferences was the timing and steps of administration. CONCLUSION: Several treatment-related characteristics, including route, frequency and complexity of the treatment, play a role in patients' preferences for T2DM treatments and should be considered during treatment selection.

Health state utilities associated with treatment process for oral and injectable GLP-1 receptor agonists for type 2 diabetes.

PURPOSE: Previous research suggests that treatment process can have an influence on patient preference and health state utilities. This study examined preferences and estimated utilities for treatment processes of two daily oral treatment regimens and two weekly injectable regimens for treatment of type 2 diabetes (T2D). METHODS: Participants with T2D in the UK reported preferences and valued four health state vignettes in time trade-off utility interviews. The vignettes had identical descriptions of T2D but differed in treatment process: (1) daily simple oral treatment (tablets without administration requirements), (2) daily oral semaglutide (with administration requirements per product label), (3) weekly dulaglutide injection, (4) weekly semaglutide injection. RESULTS: Interviews were completed by 201 participants (52.7% male; mean age = 58.7). Preferences between treatment processes varied widely. Mean utilities were 0.890 for simple oral, 0.880 for oral semaglutide, 0.878 for dulaglutide injection, and 0.859 for semaglutide injection (with higher scores indicating greater preference). All pairwise comparisons found statistically significant differences between utilities (p < 0.01), except the comparison between oral semaglutide and the dulaglutide injection (p = 0.49). CONCLUSIONS: Results suggest that routes of administration cannot be compared using only the simplest descriptions (e.g., oral versus injectable). Dose frequency and specific details of the treatment process administration had an impact on patient preference and health state utilities. The utilities estimated in this study may be useful in cost-utility models comparing these treatments for T2D. Results also suggest that it may be helpful to consider patient preferences for treatment process when selecting medications for patients in clinical settings.

Assessing patient PREFERence between the dulaglutide pen and the semaglutide pen: A crossover study (PREFER).

AIM: When selecting treatments for type 2 diabetes (T2D), it is important to consider not only efficacy and safety, but also other treatment attributes that have an impact on patient preference. The objective of this study was to examine preference between injection devices used for two weekly GLP-1 receptor agonists. MATERIALS AND METHODS: The PREFER study was an open-label, multicentre, randomized, crossover study assessing patient preference for dulaglutide and semaglutide injection devices among injection-naïve patients receiving oral medication for type 2 diabetes. After being trained to use each device, participants performed all steps of injection preparation and administered mock injections into an injection pad. Time-to-train (TTT) for each device was assessed in a subset. RESULTS: There were 310 evaluable participants (48.4% female; mean age, 60.0 years; 78 participants in the TTT subgroup). More participants preferred the dulaglutide device than the semaglutide device (84.2% vs. 12.3%; P < 0.0001). More participants perceived the dulaglutide device to have greater ease of use (86.8% vs. 6.8%; P < 0.0001). After preparing and using the devices, more participants were willing to use the dulaglutide device (93.5%) than the semaglutide device (45.8%). Training participants to use the dulaglutide device required less time than the semaglutide device (3.38 vs. 8.14 minutes; P < 0.0001). CONCLUSIONS: Participants with type 2 diabetes preferred the dulaglutide injection device to the semaglutide injection device. If patients prefer a device, they may be more willing to use the medication, which could result in better health outcomes. Furthermore, a shorter training time for injection devices may be helpful in busy clinical practice settings.

Generalizability of glucagon-like peptide-1 receptor agonist cardiovascular outcome trials to the overall type 2 diabetes population in the United States.

AIM: To examine the generalizability of results from glucagon-like peptide-1 receptor agonist (GLP-1 RA) cardiovascular outcome trials (CVOTs) in the US type 2 diabetes (T2D) population. MATERIALS AND METHODS: Patients enrolled or eligible for inclusion in four CVOTs (EXSCEL, LEADER, REWIND, and SUSTAIN-6) were examined in reference to a retrospective clinical database weighted to match the age and sex distribution of the US adult T2D population. We descriptively compared key baseline characteristics of the populations enrolled in each trial to those of the reference population and estimated the proportions of individuals in the reference population represented by those in the trials for each characteristic. We also estimated the proportions of individuals in the reference population that might have been enrolled in each trial based upon meeting the trial inclusion and exclusion (I/E) criteria. RESULTS: No trial's enrolled population perfectly matched the reference population in key characteristics. The EXSCEL population most closely matched in mean age (62.7 vs. 60.5 years) and percentage with estimated glomerular filtration rate <60 (18.6 vs. 17.3%), while REWIND most closely matched in HbA1c, sex distribution, and proportion with a prior myocardial infarction. Based on I/E criteria, 42.6% of the reference population were eligible for enrolment in REWIND, versus 15.9% in EXSCEL, 13.0% in SUSTAIN-6, and 12.9% in LEADER. CONCLUSIONS: Although none of the trials are fully representative of the general population, among the four trials examined, results from baseline REWIND were found to be more generalizable to the US adult T2D population than those of other GLP-1 RA CVOTs.

United States Valuation of EQ-5D-5L Health States Using an International Protocol.

OBJECTIVE: To derive a US-based value set for the EQ-5D-5L questionnaire using an international, standardized protocol developed by the EuroQol Group. METHODS: Respondents from the US adult population were quota-sampled on the basis of age, sex, ethnicity, and race. Trained interviewers guided participants in completing composite time trade-off (cTTO) and discrete choice experiment (DCE) tasks using the EuroQol Valuation Technology software and routine quality control measures. Data were modeled using a Tobit model for cTTO data, a mixed logit model for DCE data, and a hybrid model that combined cTTO and DCE data. Model performance was compared on the basis of logical ordering of coefficients, statistical significance, parsimony, and theoretical considerations. RESULTS: Of 1134 respondents, 1062, 1099, and 1102 respondents provided useable cTTO, DCE, and cTTO or DCE responses, respectively, on the basis of quality control criteria and interviewer judgment. Respondent demographic characteristics and health status were similar to the 2015 US Census. The Tobit model was selected as the preferred model to generate the value set. Values ranged from -0.573 (55 555) to 1 (11 111), with 20% of all predicted health states scores less than 0 (ie, worse than dead). CONCLUSIONS: A societal value set for the EQ-5D-5L was developed that can be used for economic evaluations and decision making in US health systems. The internationally established, standardized protocol used to develop this US-based value set was recommended by the EuroQol Group and can facilitate cross-country comparisons.

The Prime Diabetes Model: Novel Methods for Estimating Long-Term Clinical and Cost Outcomes in Type 1 Diabetes Mellitus.

BACKGROUND: Recent publications describing long-term follow-up from landmark trials and diabetes registries represent an opportunity to revisit modeling options in type 1 diabetes mellitus (T1DM). OBJECTIVES: To develop a new product-independent model capable of predicting long-term clinical and cost outcomes. METHODS: After a systematic literature review to identify clinical trial and registry data, a model was developed (the PRIME Diabetes Model) to simulate T1DM progression and complication onset. The model runs as a patient-level simulation, making use of covariance matrices for cohort generation and risk factor progression, and simulating myocardial infarction, stroke, angina, heart failure, nephropathy, retinopathy, macular edema, neuropathy, amputation, hypoglycemia, ketoacidosis, mortality, and risk factor evolution. Several approaches novel to T1DM modeling were used, including patient characteristics and risk factor covariance, a glycated hemoglobin progression model derived from patient-level data, and model averaging approaches to evaluate complication risk. RESULTS: Validation analyses comparing modeled outcomes with published studies demonstrated that the PRIME Diabetes Model projects long-term patient outcomes consistent with those reported for a number of long-term studies. Macrovascular end points were reliably reproduced across five different populations and microvascular complication risk was accurately predicted on the basis of comparisons with landmark studies and published registry data. CONCLUSIONS: The PRIME Diabetes Model is product-independent, available online, and has been developed in line with good practice guidelines. Validation has indicated that outcomes from long-term studies can be reliably reproduced. The model offers new approaches to long-standing challenges in diabetes modeling and may become a valuable tool for informing health care policy.

Evaluation of the impact of once weekly dulaglutide on patient-reported outcomes in Japanese patients with type 2 diabetes: comparisons with liraglutide, insulin glargine, and placebo in two randomized studies.

BACKGROUND: Standardized patient-reported outcome (PRO) questionnaires can be utilized to evaluate treatment satisfaction (subjective evaluation of treatment) in patients with type 2 diabetes (T2D). These outcomes are important because they may affect patient adherence and overall study results. METHODS: PROs were evaluated in two randomized 26-week clinical trials in Japanese patients with T2D taking dulaglutide 0.75 mg (dulaglutide) once weekly; comparators were once-daily liraglutide (0.9 mg/day) and once-weekly placebo in one study and once-daily insulin glargine (glargine) in the other study. The Perceptions About Medications-Diabetes 21 Questionnaire - Japanese version (PAM-D21-J) and the Injectable Diabetes Medication Questionnaire - Japanese version (IDMQ-J) were completed by patients in both studies. These measures were both considered exploratory endpoints. All scale scores range from 0 to 100, with higher scores reflecting better outcomes. RESULTS: Patients reported that dulaglutide was more convenient and flexible than liraglutide (PAM-D21-J Convenience/Flexibility subscale: dulaglutide least-square mean [LSM], 84.58; liraglutide LSM, 78.94; p = .026), and that they were more satisfied with dulaglutide than with liraglutide (IDMQ-J Satisfaction subscale: dulaglutide, 75.24; liraglutide, 69.53; p = .012). Patients also reported that dulaglutide was more convenient and flexible than glargine (PAM-D21-J Convenience/Flexibility subscale: dulaglutide, 87.89; glargine, 79.22; p < .001), and that they were more satisfied with dulaglutide than with glargine (IDMQ-J Satisfaction subscale: dulaglutide, 78.86; glargine, 69.66; p < .001), and felt dulaglutide was more effective than glargine, with fewer symptoms and adverse events (PAM-D21-J Perceived Effectiveness subscale: dulaglutide, 77.61; glargine, 67.22; p < .001; Emotional Effects subscale: dulaglutide, 93.02; glargine, 89.55; p = .017; IDMQ-J Blood Glucose Control subscale: dulaglutide, 76.33; glargine, 67.57; p < .001). In addition, patients responded that dulaglutide was superior to placebo in the PAM-D21-J Convenience/Flexibility, Perceived Effectiveness, and Emotional Effects subscales and all IDMQ-J subscales (Satisfaction, Ease of Use, Lifestyle Impact, Blood Glucose Control). CONCLUSIONS: Overall, after 26 weeks of once-weekly dulaglutide administration in Japanese patients with T2D, PROs were generally positive versus the three comparator treatments (liraglutide, glargine, and placebo), suggesting increased treatment satisfaction through better blood glucose control and convenience/flexibility and reduced negative emotional effects of diabetes. TRIAL REGISTRATION: ClinicalTrials.gov (monotherapy study: NCT01558271 , registered March 12, 2012; combination therapy study: NCT01584232 , registered April 23, 2012).

Health state utilities associated with attributes of weekly injection devices for treatment of type 2 diabetes.

BACKGROUND: Glucagon-like peptide-1 (GLP-1) receptor agonists are often recommended as part of combination therapy for type 2 diabetes when oral medication does not result in sufficient glycemic control. Several GLP-1 receptor agonists are available as weekly injections. These medications vary in their injection delivery systems, and these differences could impact quality of life and treatment preference. The purpose of this study was to estimate utilities associated with attributes of injection delivery systems for weekly GLP-1 therapies. METHODS: Participants with type 2 diabetes in the UK valued health states in time trade-off interviews. The health states (drafted based on literature, device instructions for use, and clinician interviews) had identical descriptions of type 2 diabetes, but differed in description of the treatment process. One health state described oral treatment, while six others described oral treatment plus a weekly injection. The injection health states varied in three aspects of the treatment administration process: requirements for reconstituting the medication (i.e., mixing the medication prior to the injection), waiting during medication preparation, and needle handling. Every participant valued all seven health states. RESULTS: A total of 209 participants completed interviews (57.4% male; mean age = 60.4y). The mean utility of the oral treatment health state was 0.89. All injection health states had significantly (p < 0.01) lower utilities ranging from 0.86 to 0.88. Differences among health state utilities suggest that each administration requirement had a small but measureable disutility: -0.004 (reconstitution), -0.004 (needle handling), -0.010 (reconstitution, needle handling), and -0.020 (reconstitution, waiting, needle handling). CONCLUSIONS: Findings suggest it is feasible to use the TTO method to quantify preferences among injection treatment processes. It may be useful to incorporate these utility differences into cost-utility models comparing weekly injectable treatments for patients with type 2 diabetes.

A qualitative examination of the content validity of the EQ-5D-5L in patients with type 2 diabetes.

BACKGROUND: The EQ-5D is frequently used to derive utilities for patients with type 2 diabetes (T2D). Despite widely available quantitative psychometric data on the EQ-5D, little is known about content validity in this population. Thus, the purpose of this qualitative study was to examine content validity of the EQ-5D in patients with T2D. METHODS: Patients with T2D in the UK completed concept elicitation interviews, followed by administration of the EQ-5D-5L and cognitive interviewing focused on the instrument's relevance, clarity, and comprehensiveness. RESULTS: A total of 25 participants completed interviews (52.0 % male; mean age = 53.5 years). Approximately half (52 %) reported that the EQ-5D-5L was relevant to their experience with T2D. When asked if each individual item was relevant to their experience with T2D, responses varied widely (24.0 % said the self-care item was relevant; 68.0 % said the anxiety/depression item was relevant). Participants frequently said items were not relevant to themselves, but could be relevant to patients with more severe diabetes. Most participants (92.0 %) reported that T2D and/or its treatment/monitoring requirements had an impact on their quality of life that was not captured by the EQ-5D-5L. Common missing concepts included food awareness/restriction (n = 13, 52.0 %); activities (n = 11, 44.0 %); emotional functioning other than depression/anxiety (n = 8, 32.0 %); and social/relationship functioning (n = 8, 32.0 %). CONCLUSIONS: The results highlight strengths and potential limitations of the EQ-5D-5L, including missing content that could be important for some patients with T2D. Suggestions for addressing limitations are provided.

Impact of caregiver and parenting status on time trade-off and standard gamble utility scores for health state descriptions.

BACKGROUND: The purpose of this study was to examine the effect of caregiver status on time trade-off (TTO) and standard gamble (SG) health state utility scores. Respondents were categorized as caregivers if they reported that either children or adults depended on them for care. METHODS: This study was a secondary analysis of data from three studies in which general population samples rated health state descriptions. Study 1: UK; four osteoarthritis health states. Study 2: UK; three adult ADHD health states. Study 3: US; 16 schizophrenia health states. All three studies included time trade-off assessment. Study 1 also included standard gamble. Descriptive statistics were calculated to examine willingness to trade in TTO or gamble in SG. Utilities for caregivers and non-caregivers were compared using t-tests and ANCOVA models. RESULTS: There were 364 respondents including 106 caregivers (n = 30, 47, and 29 in Studies 1, 2, and 3) and 258 non-caregivers. Most caregivers were parents of dependent children (78.3%). Compared to non-caregivers, caregivers had more responses at the ceiling (i.e., utility = 0.95), indicating less willingness to trade time or gamble. All utilities were higher for caregivers than non-caregivers (mean utility difference between groups: 0.07 to 0.16 in Study 1 TTO; 0.03 to 0.17 in Study 1 SG; 0.06 to 0.10 in Study 2 TTO; 0.11 to 0.22 in Study 3 TTO). These differences were statistically significant for at least two health states in each study (p < 0.05). Results of sensitivity analyses with two caregiver subgroups (parents of dependent children and parents of any child regardless of whether the child was still dependent) followed the same pattern as results of the primary analysis. The parent subgroups were generally less willing to trade time or gamble (i.e., resulting in higher utility scores) than comparison groups of non-parents. CONCLUSIONS: Results indicate that caregiver status, including being a parent, influences responses in time trade-off health state valuation. Caregivers (i.e., predominantly parents) were less willing than non-caregivers to trade time, resulting in higher utility scores. This pattern was consistent across multiple health states in three studies. Standard gamble results followed similar patterns, but with less consistent differences between groups. It may be useful to consider parenting/caregiving status when collecting, interpreting, or using utility data because this demographic variable could influence results.

Utilities for Complications Associated with Type 2 Diabetes: A Review of the Literature.

INTRODUCTION: Utility values are used in health economic modeling analyses of type 2 diabetes (T2D) to quantify the effect of acute and long-term complications on quality of life (QoL). For accurate modeling projections, it is important that the utility values used are up to date, accurate and representative of the simulated model cohort. METHODS: A literature review was performed to identify utility values for health states representing acute and chronic T2D-related complications including cardiovascular complications, stroke, renal disease, ophthalmic complications, neuropathy, diabetic foot, amputation and hypoglycemia. Searches were performed using the PubMed, Embase and Cochrane Library databases and limited to articles published since 2010. Supplementary searches were performed to identify data published at congresses in 2019-2023. RESULTS: A total of 54 articles were identified that reported utility values for T2D-related complications. The most frequently used elicitation method/instrument was the EQ-5D (n = 42 studies) followed by the Short Form-6 dimensions (n = 6), time tradeoff (n = 5), the Health Utilities Index Mark 2 or Mark 3 (n = 2), 15D (n = 1), visual analog scale (n = 1) and standard gamble (n = 1). Stroke and amputation were consistently associated with the largest decrements in QoL. There is a lack of published data that distinguishes between severity of several complications including renal disease, retinopathy and neuropathy. CONCLUSIONS: Diabetes-related complications can have a profound impact on QoL; therefore, it is important that these are captured accurately and appropriately in health economic models. Recently published utility values for diabetes-related complications that can be used to inform health economic models are summarized here.

An Economic Evaluation of the Relationship Between Glycemic Control and Total Healthcare Costs for Adults with Type 2 Diabetes: Retrospective Cohort Study.

INTRODUCTION: Glycemic control is associated with better outcomes among individuals with type 2 diabetes (T2D). This research examines total US all-cause medical costs for adults with T2D with recommended glycemic control (HbA1c < 7%) compared to poor glycemic control (HbA1c ≥ 7%). METHODS: The study used administrative claims data linked to HbA1c laboratory test results from January 1, 2015 through June 30, 2021 to identify adults with T2D with a recorded HbA1c test. Patients with recommended glycemic control at index date were propensity score matched to patients with poor glycemic control. General linear models and two-part models were used to compare all-cause outpatient, drug, acute care and total costs for 1 year post index date. RESULTS: The study included 59,830 propensity-matched individuals. Results indicate that recommended glycemic control, compared to poor glycemic control, was associated with statistically significantly lower all-cause acute care ($23,868 ± $21,776 vs. $24,352 ± $22,223), drug ($10,277 ± $14,671 vs. $10,540 ± $14,928), and total medical costs ($41,381 ± $42,757 vs. $42,054 ± $43,422) but significantly higher outpatient costs ($7290 ± $12,028 vs. $7026 ± $11,587) (all p < 0.0001). Sensitivity analyses examined results based upon alternative HbA1c thresholds of ≤ 6.5% and < 8%. Results were generally robust to alternative HbA1c thresholds, with higher HbA1c thresholds associated with higher all-cause total costs as well as increased savings for having HbA1c below threshold. CONCLUSIONS: Glycemic control was associated with significantly lower all-cause total, drug, and acute care medical costs. Given the high prevalence of T2D in the USA, our results suggest potential economic benefits associated with glycemic control for healthcare providers.

Physician Perceptions of Dose Escalation for Type 2 Diabetes Medications in the United States.

INTRODUCTION: Medications used to treat type 2 diabetes (T2D) often require dose escalation to optimize effectiveness. Physician and patient perceptions of treatment characteristics of T2D medications have previously been examined, but little is known about perceptions of escalation to the optimal dose for each patient. This study examined physicians' perceptions of dose escalation for medications used to treat T2D. METHODS: Data on dose escalation and other factors influencing decision-making for treatment of T2D were collected via an online survey of endocrinologists and primary care physicians in the USA. RESULTS: The sample included 501 physicians (348 primary care physicians and 153 endocrinologists). Dose escalation was not frequently considered by physicians as a primary factor keeping patients' from reaching treatment goals (mentioned as a factor by only 7.6% of the sample) or a barrier to prescribing T2D medication (16.2%). Factors more likely to keep patients from reaching treatment goals included an unhealthy diet (86.6%) and medication adherence (77.4%). The most common reasons that physicians reported for escalating dose levels were the need for better glycemic control (reported by 89.8% of the sample), ability to decrease the total number of medications by increasing the dose of one medication (39.9%), and the need for the patient to lose weight (39.3%). Data reported by primary care physicians and endocrinologists followed similar patterns. CONCLUSIONS: Although common with T2D treatments, escalating the dose of T2D medication was not perceived by physicians to be a significant barrier to attaining treatment goals or prescribing medication. Multiple factors contribute to the decision to escalate the dose of T2D medication.

In early phases of initiating medication treatment for a patient with type 2 diabetes (T2D), it is common for physicians to increase from a lower initial dose to a higher end dose to maximize treatment benefit. This process is known as dose escalation. The purpose of this study was to examine physicians' perceptions of dose escalation for medications used to treat T2D. An online survey was designed to identify reasons why physicians in the US may choose to escalate or not escalate a dose of medication for T2D. In addition, physicians were asked about factors that keep patients from reaching treatment goals to identify whether the requirement for dose escalation is perceived to be a common barrier to successful treatment. The sample included 501 physicians (348 primary care, 153 endocrinologists). Dose escalation was not frequently considered to be a primary factor keeping patients' from reaching treatment goals or a barrier to prescribing medication for T2D. Dose escalation decisions are complex, driven by a range of factors such as glycemic control medication tolerability, the patient's body mass index, treatment guidelines, comorbidities, characteristics of the patient's entire treatment regimen, and potential cardiovascular benefits.

Glycemic Control and Obesity Among People With Type 2 Diabetes in Europe and Australia: A Retrospective Cohort Analysis.

INTRODUCTION: In people with type 2 diabetes (PwT2D) who also have obesity, efforts targeting weight loss, including lifestyle, medication and surgical interventions, are recommended. The objective of this study was to explore the relationship between glycemic control and obesity among PwT2D in Europe and Australia using recent real-world data and applying consistent methodology across countries. METHODS: Retrospective study utilizing IQVIA electronic medical records (EMR) databases grouped into panels based on specialty of contributing physicians. General practitioner (GP) and endocrinologist/diabetologist (E/D) panels were used in Germany and France, while GP panels were used in Italy, UK and Australia. The Spanish database included all physician specialties. The sample included PwT2D with glycated hemoglobin A1c (HbA1c) and body mass index (BMI) values measured within 90 days of each other between January 2015 and December 2018 (second record termed the 'index date'). PwT2D had a 1-year baseline period and a recorded HbA1c at the end of the 1-year post-index period. RESULTS: The final sample comprised 194,729 PwT2D. At baseline, across countries/panels, 36.8-58.0% were above HbA1c target (HbA1c ≥ 7%) and 39.4-56.7% had obesity (BMI ≥ 30.0 kg/m2). Mean HbA1c ranged from 6.9 to 7.6% and mean BMI ranged from 29.3-31.6 kg/m2. At baseline, a higher proportion of PwT2D with obesity (40.8-64.2%) were above HbA1c target compared to their counterparts without obesity (32.2-52.4%). A higher proportion of patients with obesity at baseline (38.1-60.6%) had post-index HbA1c above target compared to their counterparts without obesity (30.9-56.0%). In logistic regression, patients with obesity had substantially lower odds of post-index HbA1c below target compared to those without obesity in all countries/panels except for France (E/D), Spain and Australia. CONCLUSIONS: This study presents data on HbA1c and BMI among type 2 diabetes (T2D) populations in Europe and Australia. A notable proportion of PwT2D had obesity and were above HBA1c target. Higher BMI was associated with poorer glycemic control.