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.

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.

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.

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.

Health state utilities associated with weight loss: preferences of people with type 2 diabetes and obesity in Japan.

AIMS: Health state utilities associated with weight change are needed for cost-utility analyses (CUAs) examining the value of treatments for type 2 diabetes and obesity. Previous studies have estimated the utility benefits associated with various amounts of weight reduction in the US and Europe, but preferences for weight change in Asian cultures may differ from these published values. The purpose of this study was to estimate utilities associated with reductions in body weight based on preferences of individuals with type 2 diabetes and obesity in Japan. METHODS: Health state vignettes represented type 2 diabetes with respondents' own current weight and weight reductions of 2.5%, 5%, 7.5%, 10%, 12.5%, 15%, and 20%. Utilities were elicited in time trade-off interviews with a sample of respondents in Japan with type 2 diabetes and body mass index (BMI) ≥25 kg/m2 (the cutoff for obesity in Japan). RESULTS: Analyses were conducted with data from 138 respondents (84.8% male; mean age = 58.0 years; mean BMI = 29.4 kg/m2) from all eight regions of Japan. Utility gains gradually increased with rising percentage of weight reductions ranging from 2.5% to 15%. Weight reductions of 2.5% to 15% resulted in utility increases of 0.013 to 0.048. The health state representing a 20% weight reduction yielded a wide range of preferences (mean utility increase of 0.044). Equations are recommended for estimating utility change based on any percentage of weight reduction (up to 20%) in Japanese people with type 2 diabetes and obesity. LIMITATIONS: This study was conducted in a sample with limited representation of patients with BMI >35 kg/m2 (n = 13) and relatively few women (n = 21). CONCLUSION: Results may be used to provide inputs for CUAs examining the value of treatments that are associated with weight loss in patients with type 2 diabetes and obesity in Japan.

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.

Relationship between financial impact and coverage of drugs in Australia.

OBJECTIVES: The aim of this study was to estimate the relationship between the financial impact of a new drug and the recommendation for reimbursement by the Australian Pharmaceutical Benefits Advisory Committee (PBAC). METHODS: Data in the PBAC summary database were abstracted for decisions made between July 2005 and November 2009. Financial impact-the upper bound of the values presented in the PBAC summary database-was categorized as ≤A$0, >A$0 up to A$10 million, A$10 million up to A$30 million, and >A$30 million per year. Descriptive, logistic, survival, and recursive partitioning decision analyses were used to estimate the relationship between the financial impact of a new drug indication and the recommendation for reimbursement. Multivariable analyses controlled for other clinical and economic variables, including cost per quality-adjusted life-year gained. RESULTS: Financial impact was a significant predictor of the recommendation for reimbursement. In the logistic analysis, the odds ratios of reimbursement for drug submissions with financial impacts ≥A$10 million to ≥A$30 million or >A$0 to

Development of a Patient-Reported Outcome (PRO) Measure to Assess Emotional Impact of Treatment for Type 2 Diabetes.

INTRODUCTION: Patients receiving treatment for type 2 diabetes (T2D) may experience an emotional impact associated with treatment-related changes. A patient-reported outcome (PRO) measure assessing both positive and negative emotional impact of medication treatment for T2D is needed to better understand the patient experience of treatment. The purpose of this qualitative study was to explore the emotional impact of treatment for T2D and support the development of a questionnaire to assess the emotional impact of treatment for T2D. METHODS: Exit interviews were conducted with patients with T2D participating in the SURPASS-2 and SURPASS-3 trials for tirzepatide. The exit interviews included a concept elicitation section focusing on the emotional impact of their study treatment. Results were used to develop two questionnaires that were evaluated in cognitive interviews with patients with T2D. RESULTS: The concept elicitation interviews included 28 patients (mean age 57.6 years; 64.3% female). Most patients reported positive changes in emotions associated with tirzepatide, including increased confidence (n = 23; 82.1%), hope (n = 23; 82.1%), self-esteem (n = 23; 82.1%), relief (n = 22; 78.6%), optimism (n = 21; 75.0%), sense of control (n = 21; 75.0%), happiness (n = 15; 53.6%), and motivation (n = 15; 53.6%), as well as reduced worry/anxiety (n = 19; 67.9%). Negative emotional impact was less commonly reported but included frustration (n = 2; 7.1%), worry/anxiety (n = 1; 3.6%), fear (n = 1; 3.6%), and feeling depressed (n = 1; 3.6%). Two new PROs, the Emotional Impact of Diabetes Treatment Questionnaires (EIDTQ, status and comparison versions), were developed based on these finding. The status version assesses the emotional impact of current treatment, while the comparison version allows for comparison of the current treatment to a previous treatment. The questionnaires were refined on the basis of cognitive interviews with 20 additional patients (mean age 58.3 years; 60.0% female), and results suggest that the final instruments were clear, comprehensible, and relevant to patients. CONCLUSION: The EIDTQ-Status and Comparison measures can be used as a supplement to clinical outcomes, such as hemoglobin A1c (HbA1c) and body weight, to provide a broader picture of the patient's emotional experience with medication treatment for T2D.

Medical treatment can have broad effects beyond symptom improvement, including an emotional impact. Emotional impact is subjective and therefore can only be assessed from the patient perspective. However, there is no previously published patient-reported outcome measure assessing both positive and negative emotional impact of medication treatment for type 2 diabetes. Thus, the purpose of this study was to conduct qualitative research to support the development of two new patient-reported outcome measures designed to assess the emotional impact of type 2 diabetes. Overall, the results add to previous research indicating that treatment for type 2 diabetes can have an emotional impact. The newly developed Emotional Impact of Diabetes Treatment Questionnaires were designed to assess this emotional impact, and current qualitative results support the content validity of these instruments in patients with type 2 diabetes. These instruments can be used as a supplement to clinical outcomes, such as HbA1c and body weight, to provide a broader picture of the patient's experience with medication treatment for type 2 diabetes.

Development of a patient-reported outcome (PRO) measure to assess patient perceptions of simplicity and complexity of treatment for type 2 diabetes.

INTRODUCTION: Treatments for type 2 diabetes vary widely in their complexity. The simplicity or complexity of a treatment regimen may have an impact on patient preference, treatment adherence, and health outcomes. The purpose of this qualitative study was to develop two draft patient-reported outcome instruments focusing on patients' experience with simplicity and complexity of treatment for type 2 diabetes. METHODS: The instruments were developed in a series of steps: gather information to support development of a concept elicitation interview guide (literature review and expert interviews), concept elicitation interviews with patients (N = 30), cognitive interviews with patients (N = 20), and a translatability assessment. RESULTS: In concept elicitation interviews, patients with type 2 diabetes reported a range of treatment attributes that influence their perceptions of treatment simplicity and complexity, such as injection devices, medication preparation, dose timing, dose frequency, ease of taking the correct dose, flexibility of dose schedule, remembering to take medication, and food requirements. Two draft questionnaires were developed based on the literature review, expert interviews, and concept elicitation interviews with patients. Revisions were made to these draft instruments based on qualitative interviews with patients and translatability assessment. DISCUSSION: The qualitative research conducted in this study supports the content validity of two newly developed instruments, the Simplicity of Diabetes Treatment Questionnaire (Sim-Q) and the Simplicity of Diabetes Treatment Questionnaire-Comparison (Sim-Q-Comp), designed to assess the simplicity and complexity of diabetes treatment from the patient's perspective.

Treatments for type 2 diabetes vary widely in their complexity, and previous research suggests that simpler treatments may have benefits for patients, such as better medication adherence and improved glycemic control. Despite the benefits of treatment simplicity, there are limited options for assessing simplicity of treatment from the patient perspective. This study was designed to develop two patient-reported outcome measures that assess simplicity and complexity of treatment for type 2 diabetes. Thirty patients with type 2 diabetes reported a range of treatment attributes that influence their perceptions of treatment simplicity and complexity. These attributes included injection devices, medication preparation, dose timing, dose frequency, ease of taking the correct dose, flexibility of dose schedule, and food requirements. Two questionnaires were developed based on literature review, expert interviews, and patient interviews (one questionnaire for rating a single treatment, and another questionnaire for comparing two treatments). Revisions were made to the draft instruments based on feedback from 20 additional participants and a translatability assessment. The resulting instruments are called the Simplicity of Diabetes Treatment Questionnaire (Sim-Q) and Simplicity of Diabetes Treatment Questionnaire-Comparison (Sim-Q-Comp). Future research with more patients is needed to further examine the psychometric properties of the questionnaires.

Improved Glycaemic and Weight Management Are Associated with Better Quality of Life in People with Type 2 Diabetes Treated with Tirzepatide.

INTRODUCTION: Limited data are available on the relationship between quality of life (QoL) change and significant degrees of reduction in glycated haemoglobin (HbA1c) and/or weight loss in people with type 2 diabetes (T2D). We explored the associations between HbA1c targets and/or weight loss achieved and patient-reported outcomes (PROs) in adults with T2D treated with tirzepatide, a first-in-class once weekly glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist, using pooled data from SURPASS-1 to -5 Phase 3 clinical trials. METHODS: PROs were assessed using five instruments at baseline and endpoint (Week 40 in SURPASS-1, -2 and -5; Week 52 in SURPASS-3 and -4): Impact of Weight on Quality of Life-Lite Clinical Trials Version; Impact of Weight on Self-Perception (IW-SP) questionnaire; Ability to Perform Physical Activities of Daily Living (APPADL); Diabetes Treatment Satisfaction Questionnaire change; and EQ-5D-5L. All PROs were assessed in participants receiving pooled doses of tirzepatide (5, 10 or 15 mg) and achieving HbA1c targets of < 5.7%, ≥ 5.7-≤ 6.5% and > 6.5% or achieving ≥ 0-< 5%, ≥ 5-< 10%, ≥ 10-< 15% and ≥ 15% weight loss from baseline at endpoint. The APPADL, IW-SP and EQ visual analogue scores were evaluated in participants achieving each combination of HbA1c target and weight loss. RESULTS: Achievement of lower HbA1c targets or higher body weight percentage losses were each associated with greater improvements in QoL than achievement of higher HbA1c targets or lower body weight percentage losses, respectively. Achievement of lower HbA1c targets in combination with greater weight loss was generally associated with the best QoL ratings. CONCLUSIONS: Our findings demonstrate that HbA1c targets and significant percentage body weight reduction thresholds need to be achieved for people with T2D to help substantially increase their overall health-related QoL. Tirzepatide treatment may allow a high proportion of people with T2D to achieve these targets, enabling improved QoL. CLINICAL TRIAL REGISTRATION: SURPASS-1: NCT03954834; SURPASS-2: NCT03987919; SURPASS-3: NCT03882970; SURPASS-4: NCT03730662; SURPASS-5: NCT04039503.

Limited data exist about the relationship between quality of life (QoL) and changes in clinical measures, for example management of blood sugar levels and weight, in people with type 2 diabetes. We explored the associations between glucose and weight loss targets achieved and QoL outcomes reported by adults treated with tirzepatide, the first glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist approved for the treatment of people with type 2 diabetes, using data from SURPASS-1 to -5 Phase 3 clinical trials.Five questionnaires, developed to evaluate patients' health-related QoL, were completed by patients at the beginning and end of the clinical trials, which was after 40 weeks for SURPASS-1, -2 and -5 and after 52 weeks for SURPASS-3 and -4, or when the person left the trial if this was before the official end. These questionnaires were: EQ-5D-5L (SURPASS-1 to -5); Impact of Weight on Self-Perception questionnaire (SURPASS-1 to -5); Ability to Perform Physical Activities of Daily Living (SURPASS-1 to -5); Diabetes Treatment Satisfaction Questionnaire change (SURPASS-2 to -5); and Impact of Weight on Quality of Life­Lite Clinical Trials Version (SURPASS-2 only).Overall, achievement of lower glucose targets or higher percentage of body weight losses were each associated with greater improvements in QoL. Achievement of lower glucose targets in combination with greater weight loss was generally associated with the highest health-related QoL ratings.Tirzepatide treatment may allow a high proportion of people with type 2 diabetes to achieve lower glucose levels and higher weight loss, enabling improved health-related QoL.