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BACKGROUND: Approximately 7.3 million people with type 1 or type 2 diabetes (T1D/T2D) are treated with insulin, placing them at higher risk of severe hypoglycemia (SH). SH requires assistance of another individual and often necessitates the prompt administration of intravenous glucose, injectable glucagon, or both. Untreated, SH can progress to unconsciousness, seizures, coma, or death. Before 2018, all glucagon rescue treatments required reconstitution. The complexity of reconstitution is often a barrier to successful administration during a severe hypoglycemic event. Studies suggest successful administration of glucagon emergency kits range from 6%-56% of the time. Second-generation glucagon treatments and glucagon analogs do not require reconstitution and have caregiver administration success rates ranging from 94%-100%. Dasiglucagon is a glucagon analog administered via autoinjector or prefilled syringe and has been shown to result in rapid hypoglycemia recovery. Moreover, the autoinjector can be administered successfully 94% of the time by trained caregivers. Previous evaluation of costs in budget impact models (BIMs) demonstrated the potential for second-generation glucagon treatments to reduce the cost of SH events (SHEs). The current model expands on those findings with a treatment pathway and accompanying assumptions reflecting important aspects of real-world SHE treatment. OBJECTIVE: To evaluate the economic impact of dasiglucagon compared with available glucagon treatments for SHE management, considering direct cost of treatment and health care resource utilization. METHODS: A 1-year BIM with a hypothetical US commercial health plan of 1 million lives was developed with a target population of individuals with diabetes at risk of SHE. The treatment pathway model included initial and secondary treatment attempts, treatment administration success and failure, plasma glucose (PG) recovery within 15 minutes, emergency medical services, emergency department (ED) visits, and hospitalizations. A 1-way sensitivity analysis was conducted to assess the sensitivity of the model to changes in parameter values. RESULTS: In a 1 million-covered lives population, it was estimated that 12,006 SHEs would occur annually. The higher rate of initial treatment success and PG recovery within 15 minutes associated with dasiglucagon treatment resulted in lower total health care costs. Total SHE treatment costs with dasiglucagon were estimated at $13.4 million, compared with $16.7 million for injectable native glucagon, $20.7 million for nasal glucagon, $35.3 million for reconstituted glucagon, and $43.8 million for untreated individuals. Compared with untreated people, the number needed to treat (NNT) with dasiglucagon was 6 individuals to avoid 1 hospitalization. NNT for this same comparison was 59 for injectable native glucagon and 27 for nasal glucagon. CONCLUSIONS: Treatment of SH with dasiglucagon decreased total direct medical costs by reducing health care resource utilization (emergency calls, emergency transports, ED visits, and hospitalizations) and accompanying costs associated with the treatment of SH. DISCLOSURES: This research was funded by Zealand Pharma. Bromley, Hinahara, and Goss are employed by Boston Healthcare Associates, Inc., which received funding from Zealand Pharma for development of the health economic model and the manuscript. Kendall and Hammer are employed by Zealand Pharma. Weinzimer has received consulting fees from Zealand Pharma.

Background: Severe hypoglycemic episodes are life-threatening events demanding rapid administration of glucagon by a caregiver or bystander. The glucagon analog dasiglucagon is stable in aqueous formulation and therefore suitable for delivery in a ready-to-use autoinjector, potentially increasing speed and ease of use compared with standard glucagon emergency kits (GEKs). Methods: In an open label, randomized, crossover, comparative device handling study, trained caregivers and untrained bystanders administered the dasiglucagon autoinjector or Eli Lilly GEK to manikins in a simulated emergency hypoglycemia situation. Results: In total, 54 participants were randomized (18 patient-caregiver pairs and 18 bystanders). Overall, 94% of trained caregivers were able to administer the dasiglucagon autoinjector successfully within 15 min, compared with 56% for the GEK ( P  < 0.05). A greater proportion of trained caregivers and untrained bystanders successfully prepared and administered the dasiglucagon autoinjector within 2 min compared with the GEK ( P  < 0.005 and P  < 0.05, respectively). Time to successful completion was also significantly faster with the dasiglucagon autoinjector than with the GEK ( P  < 0.005 for both groups). Most study participants preferred the dasiglucagon autoinjector over the GEK (94%, P  < 0.001) and rated it as easier (90%, P  < 0.001) and less stressful to use (94%, P  < 0.001) than the GEK. Conclusion: Dasiglucagon autoinjector was more rapidly and reliably administered, and users reported greater ease of use and usage satisfaction than with the GEK. Thus, dasiglucagon autoinjector has the potential to improve speed and ease of treatment in severe hypoglycemic events, providing a better usage experience for rescuing individuals and enabling faster recovery for patients.

Background: Congenital hyperinsulinism (CHI) is the most common cause of persistent hypoglycemia in infants and children, and carries a considerable risk of neurological damage and developmental delays if diagnosis and treatment are delayed. Despite rapid advances in diagnosis and management, long-term developmental outcomes have not significantly improved in the past years. CHI remains a disease that is associated with significant morbidity, and psychosocial and financial burden for affected families, especially concerning the need for constant blood glucose monitoring throughout patients' lives., Results: In this review, we discuss the key clinical challenges and unmet needs, and present insights on patients' and families' perspective on their daily life with CHI. Prevention of neurocognitive impairment and successful management of patients with CHI largely depend on early diagnosis and effective treatment by a multidisciplinary team of specialists with experience in the disease., Conclusions: To ensure the best outcomes for patients and their families, improvements in effective screening and treatment, and accelerated referral to specialized centers need to be implemented. There is a need to develop a wider range of centers of excellence and networks of specialized care to optimize the best outcomes both for patients and for clinicians. Awareness of the presentation and the risks of CHI has to be raised across all professions involved in the care of newborns and infants. For many patients, the limited treatment options currently available are insufficient to manage the disease effectively, and they are associated with a range of adverse events. New therapies would benefit all patients, even those that are relatively stable on current treatments, by reducing the need for constant blood glucose monitoring and facilitating a personalized approach to treatment., (© 2022. The Author(s).)

This White Paper is authored by 11 industry real-world evidence (RWE) experts, with support from IQVIA, as part of the 'RWE Leadership Forum': a group of industry leaders who come together as noncompetitive partners to understand and respond to internal or external RWD/E challenges and opportunities with a single expert voice. Herein we aim to clarify the rules of engagement between pharma and healthcare in order to establish trust-based partnerships, which will unlock unique value for society, including the medical community and the ultimate beneficiary, the patient.

Objective: To examine the association of obesity with healthcare resource utilization (HRU) and costs among commercially insured individuals., Methods: This retrospective observational cohort study used administrative claims from 1 January 2007 to 1 December 2013. The ICD-9-CM status codes (V85 hierarchy) from 2008 to 2012 classified body mass index (BMI) into the World Health Organizations' BMI categories. The date of first observed BMI code was defined as the index date and continuous eligibility for one year pre- and post- index date was ensured. Post-index claims determined individuals' HRU and costs. Sampling weights developed using the entropy balance method and National Health and Nutrition Examination Survey data ensured representation of the US adult commercially insured population. Baseline characteristics were described across BMI classes and associations between BMI categories, and outcomes were examined using multivariable regression., Results: The cohort included 9651 individuals with BMI V85 codes. After weighting, the BMI distribution was: normal (31.1%), overweight (33.4%), obese class I (22.0%), obese class II (8.1%) and obese class III (5.4%). Increasing BMI was associated with greater prevalence of cardiometabolic conditions, including hypertension, type 2 diabetes and metabolic syndrome. The use of antihypertensives, antihyperlipidemics, antidiabetics, analgesics and antidepressants rose with increasing BMI. Greater BMI level was associated with increased inpatient, emergency department and outpatient utilization, and higher total healthcare, medical and pharmacy costs., Conclusions: Increasing BMI was associated with higher prevalence of cardiometabolic conditions and higher HRU and costs. There is an urgent need to address the epidemic of obesity and its clinical and economic impacts.

Objectives: To examine the association of obesity with healthcare resource utilization and costs in a Medicare population., Methods: This study was a retrospective cohort study using Humana Medicare Advantage (MA) claims data. Body mass index (BMI) was assessed using ICD-9-CM status codes (V85 hierarchy) that have been validated in the data source to classify patients into BMI categories: normal (N), overweight (Ow), obese class I (ObI), obese class II (ObII), and obese class III (ObIII). Healthcare resource utilization (HRU) and costs were determined based on claims data. Descriptive statistics were used to examine baseline characteristics and HRU across BMI classes. Multivariable analysis was used to examine the association between BMI class and outcome measures., Results: Among the 172,866 patients aged ≥65 years that were identified, BMI distribution was: N, 21%; Ow 37%; ObI, 24%, ObII, 10%; and ObIII, 9%. Inpatient, emergency department and outpatient utilization increased with greater BMI level, and greater BMI level was associated with higher total healthcare, medical and pharmacy costs. Greater prevalence of several cardiometabolic conditions, total medication use, and use of specific medication classes was observed with increasing BMI class., Conclusions: Greater BMI was associated with greater HRU and costs and observed increase in prevalence of cardiometabolic conditions. These results reflect an urgent need to address the epidemic of obesity and the resulting excessive clinical and economic burden on the healthcare system.

Objective: Liraglutide has been shown to significantly improve glycemic control and reduce body weight while minimizing the risk of hypoglycemia in adult patients with type 2 diabetes (T2D). This study aimed to identify characteristics that predict clinical and economic outcomes associated with liraglutide therapy in clinical practice in the US., Methods: Using the Truven Health MarketScan Laboratory Database, glycemic control (A1C <7%) and diabetes-related costs were evaluated in T2D patients initiating liraglutide between January 1, 2010 and June 30, 2012. Patients were required to have ≥1 post-index claim for liraglutide and A1C values at baseline and 6 months follow-up. All valid values of baseline A1C were included. Patients previously treated with GLP-1 receptor agonist(s) or insulin, or with evidence of type 1 diabetes, pregnancy, or gestational diabetes during the study period were excluded. Multivariable regression models were used to identify predictors of glycemic control and diabetes-related costs., Results: Of 417 patients newly treated with liraglutide, 54.0% achieved glycemic control (A1C <7%) during follow-up. Factors associated with increased odds of glycemic control during follow-up were: being female, POS/EPO health plan type, baseline A1C, early liraglutide initiation (0-1 prior oral anti diabetics [OADs] vs ≥2), adherence to liraglutide (defined as the proportion of days covered [PDC]), and diabetic retinopathy. Being female, earlier liraglutide initiation (0-1 prior OADs), and higher patient share of liraglutide costs were associated with significantly lower diabetes-related costs during follow-up. Factors associated with significantly higher post-index diabetes-related costs were: higher baseline A1C, baseline use of sulfonylureas, and diabetic retinopathy., Conclusions: Within this commercially-insured population of T2D patients treated with liraglutide, gender, baseline A1C, early liraglutide initiation (0-1 prior OADs), diabetic retinopathy, better adherence, and patient share of liraglutide costs were associated with increased odds of achieving glycemic control and the odds of having higher or lower diabetes-related costs.

Most research on the economic consequences of obesity uses data on self-reported weight, which contains reporting error that has the potential to bias coefficient estimates in economic models. The purpose of this paper is to measure the extent and characteristics of reporting error in weight, and to examine its impact on regression coefficients in models of the healthcare consequences of obesity. We analyze data from the National Health and Nutrition Examination Survey (NHANES) for 2003-2010, which includes both self-reports and measurements of weight and height. We find that reporting error in weight is non-classical: underweight respondents tend to overreport, and overweight and obese respondents tend to underreport, their weight, with underreporting increasing in measured weight. This error results in roughly 1 out of 7 obese individuals being misclassified as non-obese. Reporting error is also correlated with other common regressors in economic models, such as education. Although it is a common misconception that reporting error always causes attenuation bias, comparisons of models that use self-reported and measured weight confirm that reporting error can cause upward bias in coefficient estimates. For example, use of self-reports leads to overestimates of the probability that an obese man uses a prescription drug, has a healthcare visit, or has a hospital admission. These findings underscore that models of the consequences of obesity should use measurements of weight, when available, and that social science datasets should measure weight rather than simply ask subjects to report their weight., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Objective: The objective of this study is to provide current estimates of the association between obesity and health outcomes and to examine these associations among subgroups of interest (pre-diabetes, type 2 diabetes [T2D], and neither pre-diabetes nor T2D) in the United States., Methods: Data were analyzed from the 2013 US National Health and Wellness Survey (N = 71,530). Respondents were categorized by body mass index (BMI) class (normal, overweight, obese class I, obese class II, obese class III)., Results: As BMI increased, health status decreased significantly (and to a clinically relevant degree) for respondents categorized as obese compared with normal weight. Work productivity impairment, physician visits, emergency room visits, and costs also increased significantly as BMI increased. The pattern of results was similar across the three subgroups., Conclusions: Increasing BMI was associated with decreasing health status and increasing work-related impairment, healthcare resource utilization, and costs.

Background: The prevalence of obesity has more than doubled in the USA in the past 30 years. Obesity is a significant risk factor for diabetes, cardiovascular disease, and other clinically significant co-morbidities. This paper estimates the medical care cost savings that can be achieved from a given amount of weight loss by people with different starting values of body mass index (BMI), for those with and without diabetes. This information is an important input into analyses of the cost effectiveness of obesity treatments and prevention programs., Methods: Two-part models of instrumental variables were estimated using data from the Medical Expenditure Panel Survey (MEPS) for 2000-2010. Models were estimated for all adults as well as separately for those with and without diabetes. We calculated the causal impact of changes in BMI on medical care expenditures, cost savings for specific changes in BMI (5, 10, 15, and 20 %) from starting BMI levels ranging from 30 to 45 kg/m(2), as well as the total excess medical care expenditures caused by obesity., Results: In the USA, adult obesity raised annual medical care costs by $US3,508 per obese individual, for a nationwide total of $US315.8 billion (year 2010 values). However, the relationship of medical care costs over BMI is J-shaped; costs rise exponentially in the range of class 2 and 3 obesity (BMI ≥35). The heavier the obese individual, the greater the reduction in medical care costs associated with a given percent reduction in BMI. Medical care expenditures are higher, and rise more with BMI, among individuals with diabetes than among those without diabetes., Conclusions: The savings from a given percent reduction in BMI are greater the heavier the obese individual, and are greater for those with diabetes than for those without diabetes. The results provide health insurers, employers, government agencies, and health economists with accurate estimates of the change in medical care expenditures resulting from weight loss, which is important information for calculating the cost effectiveness of interventions to prevent and treat obesity.

Background: Electronic medical records and insurance claims data from the Geisinger Health System were examined to assess the real-world healthcare costs of being overweight or obese at different glycemic stages, including normal glycemia, pre-diabetes (PreD), and type 2 diabetes (T2D)., Methods: The medical history of the sample subjects was segmented into different glycemic stages via diagnosis codes, glycosylated hemoglobin A1c or fasting plasma glucose laboratory results, and use of antidiabetic drugs. Healthcare resource utilization captured by the claims and associated costs (in 2013 values) were examined for each glycemic stage. The association between costs and body mass index (BMI) was estimated by regressions, and adjusted for sociodemographics. We predicted the adjusted incremental annual costs associated with high BMI, relative to normal BMI (18.5-24.9 kg/m(2))., Results: We identified 48,344 adults in normal glycemic stage, 3,085 in the PreD stage, and 9,526 in the T2D stage (mean age 46, 58, and 60 years, respectively; mean BMI 29, 32, and 33 kg/m(2), respectively). The adjusted incremental annual costs associated with high BMI relative to normal BMI ranged from $336 for overweight (25-29.9 kg/m(2)) to $1,850 for class III obesity (≥40 kg/m(2)) during normal glycemic stage; were only significant for class III ($2,434) during the PreD stage; and ranged from $1,139 for overweight to $4,649 for class III during the T2D stage (all p < 0.05)., Conclusions: Positive associations between healthcare costs and BMI levels were observed within each glycemic stage. Management of body weight is important in reducing the overall healthcare costs, especially for subjects with PreD or T2D.

Introduction: Adherence to diabetes medication has been linked to improved glycemic levels and lower costs, but previous research on adherence has typically involved oral antidiabetic medication or insulin. This study examines how adherence and persistence to once-daily liraglutide impact glycemic control and economic outcomes in a real-world population of adult type 2 diabetes (T2D) patients., Methods: A retrospective cohort study using administrative claims data from July 2009 through September 2013. Patients aged ≥18 years with T2D treated with liraglutide were identified (index date = first liraglutide prescription). Adherence was based on the proportion of days covered (PDC); with PDC ≥0.80 classified as adherent. Non-persistent patients were those with a gap in therapy of >90 days. Lab results for glycated hemoglobin (A1C) were used to identify whether patients achieved target levels of <7.0% and ≤ 6.5%, or experienced a reduction of ≥1.0% in A1C from pre-index (baseline) to post-index (follow-up). Logistic regression was used to estimate the likelihood of achieving the A1C goals, adjusted for baseline characteristics. Diabetes-related medical, pharmacy, and total costs were modeled and estimated for the adherence and persistence cohorts., Results: A total of 1321 patients were identified. The mean PDC was 0.59 and 34% of patients were classified as adherent, while 60% were persistent over 12 months of follow-up. Adherent and persistent patients were more likely to achieve each of the A1C goals than their non-adherent and non-persistent counterparts after adjusting for patient characteristics. Adherence and persistence were associated with higher adjusted diabetes-related pharmacy and total healthcare costs during follow-up; whereas persistent patients had significantly lower diabetes-related medical costs than non-persistent patients., Conclusions: Adherence and persistence to liraglutide are associated with improved A1C outcomes. Persistent patients showed significantly lower medical costs versus those discontinuing liraglutide. Total healthcare costs were higher for adherent and persistent cohorts driven by higher pharmacy costs.

Objective: This study estimated the economic burden of obesity-related comorbidities (ORCs) in the US, at both the person and population levels., Methods: The Geisinger Health System provided electronic medical records and claims between January 2004 and May 2013 for a sample of 153,561 adults (50% males and 97% white). Adults with < 2 years of data, who were underweight (body mass index (BMI) < 18.5 kg/m(2)), or had diseases causing major weight change (e.g., malignancy) during the study period (i.e., continuous enrollment in health plans) were excluded. A total of 21 chronic conditions, with established association with obesity in the literature, were identified by diagnosis codes and/or lab test results. The total healthcare costs were measured in each year. The association between annual costs and ORCs was assessed by a regression, which jointly considered all the ORCs. The per-person incremental costs of a single comorbidity, without any of the other ORCs, were calculated. The population-level economic burden was the product of each ORC's incremental costs and the annual prevalence of the ORC among 100,000 individuals. The prevalence of ORCs was stratified by obesity status to estimate the economic burden among 100,000 individuals with obesity and among those without., Results: This study identified 56,895 adults (mean age = 47 years; mean BMI = 29.6 kg/m(2)). The annual prevalence of ORCs ranged from 0.5% for pulmonary embolism (PE) to 41.8% for dyslipidemia. The per-person annual incremental costs of a single ORC ranged from $120 for angina to $1665 for PE. Hypertensive diseases (HTND), dyslipidemia, and osteoarthritis were the three most expensive ORCs at the population level; each responsible for ≥$18 million annually among 100,000 individuals. HTND and osteoarthritis were much more costly among individuals with obesity than those without obesity., Limitations: Data were from a small geographic region., Conclusions: ORCs are associated with substantial economic burden, especially for those requiring continuous treatments.

Objective: The purpose of this study was to assess how the risks of glycemic stage transitions observed in clinical practice vary with body mass index (BMI). These transitions included progression from euglycemia ('normal') to prediabetes (PreD) and from PreD to type 2 diabetes (T2D), as well as from normal directly to T2D, and reversions from PreD to normal., Methods: We examined the Geisinger Health System electronic health records and insurance claims data, segmenting a subject's medical history into normal, PreD, and/or T2D glycemic stages via diagnosis codes, glycosylated hemoglobin A1c (HbA1c) or fasting plasma glucose lab results, and use of anti-diabetic drugs. Weibull survival models, adjusted for age, gender, race, and smoking, were used to estimate the glycemic progression hazard ratios for BMI categories relative to normal BMI., Results: The sample included 32,864 adults with normal glycemic levels at baseline and 4483 with PreD. The adjusted hazard ratios for normal to PreD progression ranged from 1.8 (25 ≤ BMI < 30 kg/m(2)) to 6.5 (BMI ≥ 40 kg/m(2)); for PreD to T2D, 1.3 to 2.9; for normal to T2D, 1.8 to 9.5; and for PreD to normal, ∼0.7 across all BMI., Limitations: The glycemic transitions may be recognized after the true onset since periodic glycemic testing was not required across the study population., Conclusions: A positive association between the risks of progression along the glycemic continuum and BMI levels was observed in a real-world United States practice setting.

Introduction: The objective of this study was to compare the clinical effectiveness of liraglutide with sitagliptin and assess the associated economic outcomes in patients with type 2 diabetes mellitus (T2DM) treated in real-world practice in the United States (US)., Methods: This retrospective cohort study used a large US claims database to identify patients with T2DM who initiated liraglutide or sitagliptin between January 2010 and December 2012. Adults (≥18 years old) with persistent use of therapy for ≥3 months were included. Changes in glycated hemoglobin A1c (A1C) and the proportion of patients achieving A1C targets (≤6.5% and <7%) were examined at 6-month follow-up. Diabetes-related total, medical, and pharmacy costs over the follow-up period were assessed. Multivariable regression models were used to estimate the outcomes associated with liraglutide relative to sitagliptin, adjusting for differences in patient demographics and clinical characteristics., Results: The study included 1,465 patients with T2DM who initiated liraglutide (N = 376) or sitagliptin (N = 1,089) (mean age [standard deviation (SD)]: 54 [8.9] vs. 58 [10.8] years; 43.9% vs. 61.8% males; both P < 0.01). After controlling for confounding factors, liraglutide patients experienced 0.31% points greater reduction in A1C (0.95% vs. 0.63% points; P < 0.01) at 6-month follow-up than sitagliptin patients and were more likely to reach A1C targets of ≤6.5% (odds ratio [OR]: 2.00; P < 0.01) and <7% (OR: 1.55; P < 0.01). Liraglutide patients had $994 lower mean diabetes-related medical costs ($1,241 vs. $2,235; P < 0.01), but $544 higher diabetes-related pharmacy costs ($2,100 vs. $1,556; P < 0.01) during the follow-up. No difference was found in the total mean diabetes-related costs between the two cohorts., Conclusion: Liraglutide showed greater improvement in glycemic outcomes than sitagliptin among adult patients with T2DM in real-world clinical practice. Although diabetes-related pharmacy costs for patients using liraglutide were higher compared with sitagliptin, these were offset by significantly lower diabetes-related medical costs, resulting in similar total diabetes-related costs between the two treatment groups.

Introduction: Clinical trials have shown that liraglutide effectively lowers glycated hemoglobin A1c (A1C) levels in adult patients with type 2 diabetes (T2D). However, no studies have evaluated the effectiveness of liraglutide by body mass index (BMI) in the United States (US) in clinical practice. This study examined liraglutide's clinical effectiveness to lower A1C and body weight after 6 months in T2D patients stratified by baseline BMI., Methods: This was a retrospective cohort study using the General Electric Centricity electronic medical records database. Adult patients with T2D (≥18 years and BMI≥ 25 kg/m(2)) and A1C >7% at baseline who started liraglutide between January 1, 2010 and January 31, 2013 and who did not use insulin or a glucagon-like peptide-1 analog 12 months before initiating liraglutide (N = 3,005) were selected. Changes from baseline, stratified by BMI, in A1C, body weight, A1C <7% goal attainment, and incidence of severe hypoglycemia at 6-month follow-up were examined., Results: After 6 months, A1C levels decreased on average by 0.95%, 1.02%, 0.99%, and 0.84% for BMI categories 25.0-29.9 (n = 333), 30.0-34.9 (n = 793), 35.0-39.9 (n = 821), and ≥40.0 kg/m(2) (n = 1,058), respectively (P = 0.30). The proportions of patients achieving A1C <7% at 6 months were 38.2%, 37.0%, 40.9%, and 41.0% (P = 0.54). The absolute body weight decreased by 1.5 to 4.0 kg across BMI and the rate of severe hypoglycemia (0.2%) was low., Conclusion: Patients with T2D experienced statistically significant decreases in A1C and body weight after initiating liraglutide regardless of their BMI. Liraglutide reduced A1C equally well across baseline BMI in clinical practice in the US.

Objectives: Obesity is a known risk factor for type 2 diabetes (T2D). We conducted a case-control study to assess the association between body mass index (BMI) and the risk of being diagnosed with T2D in the United States., Methods: We selected adults (≥ 18 years old) who were diagnosed with T2D (defined by ICD-9-CM diagnosis codes or use of anti-diabetic medications) between January 2004 and October 2011 ("cases") from an electronic health records database provided by an integrated health system in the Middle Atlantic region. Twice as many individuals enrolled in the health system without a T2D diagnosis during the study period ("controls") were selected based on age, sex, history of cardiac comorbidities or hyperinflammatory state (defined by C-reactive protein and erythrocyte sedimentation rate), and use of psychiatric or beta blocker medications. BMI was measured during one year prior to the first observed T2D diagnosis (for cases) or a randomly assigned date (for controls); individuals with no BMI measure or BMI < 18.5 kg/m2 were excluded. We assessed the impact of increased BMI (overweight: 25-29.9 kg/m2; Obesity Class I: 30-34.9 kg/m2; Obesity Class II: 35-39.9 kg/m2; Obesity Class III: ≥40 kg/m2), relative to normal BMI (18.5-24.9 kg/m2), on a T2D diagnosis using odds ratios (OR) and relative risks (RR) estimated from multiple logistic regression results., Results: We included 12,179 cases (mean age: 55, 43% male) and 25,177 controls (mean age: 56, 45% male). We found a positive association between BMI and the risk of a T2D diagnosis. The strength of this association increased with BMI category (RR [95% confidence interval]: overweight, 1.5 [1.4-1.6]; Obesity Class I, 2.5 [2.3-2.6]; Obesity Class II, 3.6 [3.4-3.8]; Obesity Class III, 5.1 [4.7-5.5])., Conclusions: BMI is strongly and independently associated with the risk of being diagnosed with T2D. The incremental association of BMI category on the risk of T2D is stronger for people with a higher BMI relative to people with a lower BMI.

Purpose: Responsiveness is defined as the ability of an instrument to accurately detect change when it has occurred and is an essential psychometric property of a patient-reported outcomes (PRO) measure to understand and interpret study findings. This study examined the responsiveness of 2 Treatment Related Impact Measures (TRIMs): The TRIM-Diabetes (TRIM-D) and TRIM-Diabetes Device (TRIM-DD) as well as confirmed their measurement models in a randomized controlled trial (RCT) design., Methods: The data were collected in a multi-center, randomized, open-label (2 × 12 week), cross-over study of two prefilled pens in subjects with type 1 or type 2 diabetes, age 18 or older. Internal and external responsiveness were examined. To confirm the measurement model identified in the previous study, the Bentler comparative fit index (CFI) and internal consistency for the RCT sample scores were examined and compared., Results: Based on a priori criteria, tests of responsiveness were confirmed with patients having significant improvements over time ranging from 2.7 (Psychological Health) to 11.1 (Treatment Burden) (P < 0.01) (effect sizes ranging from 0.2 to 0.8). The previous measurement model factor structure was confirmed (CFI ranging from 0.8 to 1.0), and internal consistency of the TRIMs was similar to the developmental findings., Conclusions: The total score as well as all domain scores of the TRIMs was significantly responsive over time, thus acceptable internal and external responsiveness of TRIM-D and TRIM-DD are concluded. To date, all validation evidence supports the use of these two measures in future clinical trials.

Background: Nearly half of all US patients with type 2 diabetes mellitus (T2DM) are unable to maintain adequate glycosylated hemoglobin (HbA₁(c)) control (ie, <7.0%)., Objective: The aim of this work was to determine the long-term cost-effectiveness of incretin-based therapy with once-daily liraglutide (vs twice-daily exenatide) combined with metformin, glimepiride, or both for the treatment of T2DM., Methods: Patient data were obtained from the Liraglutide Effect and Action in Diabetes 6 (LEAD 6) trial. Baseline data included mean HbA₁(c) (8.15%), age (56.7 years), disease duration (8 years), sex, body mass index, blood pressure, lipid levels, cardiovascular and renal risk factors, and other complications. The IMS Center for Outcomes Research Diabetes Model was used to project and compare lifetime (ie, 35-year) clinical and economic outcomes for once-daily liraglutide 1.8 mg compared with twice-daily exenatide 10 (ig, each used as add-on therapy with maximum-dose metformin and/or glimepiride. Treatment-effect assumptions were also derived from the LEAD 6 trial. Transition probabilities, utilities, and complication costs were obtained from published sources. All outcomes were discounted at 3% per annum, and the analysis was conducted from the perspective of a third-party payer in the United States., Results: The base-case analysis indicated that, compared with exenatide, liraglutide add-on therapy was associated with a mean (SD) increase in life expectancy of 0.187 (0.250) years and an increase in qualityadjusted life-years of 0.322 (0.164) years. Compared with exenatide, total lifetime treatment costs for liraglutide were $12,956 higher, yielding an incremental costeffectiveness ratio (ICER) of $40,282. However, the costs of diabetes-related complications were lower with liraglutide than with exenatide ($49,784 vs $52,429, respectively). Sensitivity analysis indicated that setting patient HbA(1c) levels at the 95% upper limit reduced the ICER for liraglutide compared with exenatide to $33,086., Conclusion: In this model analysis using published clinical data and current medication acquisition price assumptions, liraglutide (in combination with metformin and/or glimepiride) appeared to be cost-effective in the US payer setting over a 35-year time horizon., (Copyright © 2010 Excerpta Medica Inc. All rights reserved.)

Patient-reported outcomes for liraglutide or glimepiride on metformin were investigated. Patients' treatment satisfaction on liraglutide was higher than with metformin alone and comparable with glimepiride+metformin. Patients perceived lower frequency of hypoglycaemia than glimepiride+metformin and lower frequency of hyperglycaemia than metformin. Impact of weight on quality of life did not differ.

Background: The use of prescription anti-obesity medication (AOM) is becoming increasingly common as treatment options grow and become more accessible. However, AOM may not be without a wide range of potentially negative impacts on patient functioning and well being. The Treatment Related Impact Measure (TRIM-Weight) is an obesity treatment-specific patient reported outcomes (PRO) measure designed to assess the key impacts of prescription anti-obesity medication. This paper will present the validation findings for the TRIM-Weight., Methods: The online validation battery survey was administered in four countries (the U.S., U.K., Australia, and Canada). Eligible subjects were over age eighteen, currently taking a prescription AOM and were currently or had been obese during their life. Validation analyses were conducted according to an a priori statistical analysis plan. Item level psychometric and conceptual criteria were used to refine and reduce the preliminary item pool and factor analysis to identify structural domains was performed. Reliability and validity testing was then performed and the minimally importance difference (MID) explored., Results: Two hundred and eight subjects completed the survey. Twenty-one of the 43 items were dropped and a five-factor structure was achieved: Daily Life, Weight Management, Treatment Burden, Experience of Side Effects, and Psychological Health. A-priori criteria for internal consistency and test-retest coefficients for the total score and all five subscales were met. All pre-specified hypotheses for convergent and known group validity were also met with the exception of the domain of Daily Life (proven in an ad hoc analysis) as well as the 1/2 standard deviation threshold for the MID., Conclusion: The development and validation of the TRIM-Weight has been conducted according to well-defined principles for the creation of a PRO measure. Based on the evidence to date, the TRIM-Weight can be considered a brief, conceptually sound, valid and reliable PRO measure.

Objective: To use time trade-off (TTO) to compare patient preferences for profiles of two glucagon-like peptide (GLP-1) products for the treatment of type 2 diabetes (liraglutide and exenatide) that vary on four key attributes - efficacy (as measured by hemoglobin A(1C)), incidence of nausea, incidence of hypoglycemia, and dosing frequency (QD vs. BID) - and measure the contribution of those attributes to preferences., Methods: A total of 382 people with T2DM were recruited to participate in an internet-based survey consisting of a series of health-related questions, a conjoint exercise and a set of time trade-off items. In the conjoint exercise, respondents were presented with eight pairs of hypothetical GLP-1 profiles, and completed a time-tradeoff exercise for each pair., Results: The product profile representing liraglutide was preferred by 96% of respondents and resulted in significantly higher health utilities (0.038) than the product profile representing exenatide (0.978 vs. 0.94, p < 0.05). Estimated preference scores from the conjoint analysis revealed that efficacy measured by hemoglobin A(1C) is the most important attribute, followed by nausea, hypoglycemia, and dosing schedule., Limitations: On-line participants may not represent 'typical' type 2 diabetes patients, and brief product profiles represented results from clinical trials, not clinical practice, Conclusion: Based on the four attributes presented, patients prefer liraglutide over exenatide. Preference is based on superior efficacy and less nausea more than less hypoglycemia and once-daily dosing.

Background: Weight gain can contribute towards the development of type 2 diabetes (T2D), and some treatments for T2D can lead to weight gain. The aim of this study was to determine whether having T2D and also being obese had a greater or lesser impact on health-related quality of life (HRQoL) than having either of the two conditions alone., Methods: The 2003 dataset of the Health Survey for England (HSE) was analyzed using multiple regression analyses to examine the influence of obesity and T2D on HRQoL, and to determine whether there was any interaction between these two disutilities., Results: T2D reduced HRQoL by 0.029 points, and obesity reduced HRQoL by 0.027 points. There was no significant interaction effect between T2D and obesity, suggesting that the effect of having both T2D and being obese is simply additive and results in a reduction in HRQoL of 0.056., Conclusions: Based on analysis of HSE 2003 data, people with either T2D or obesity experience significant reduction in HRQoL and people with both conditions have a reduction in HRQoL equal to the sum of the two independent effects. The effect of obesity on HRQoL in people with T2D should be considered when selecting a therapy.

Study Objective: To project and compare long-term outcomes of morbidity and mortality, and costs of complications of type 2 diabetes mellitus from a randomized controlled trial of patients receiving liraglutide versus glimepiride monotherapy., Design: Mathematic simulation using the validated Center for Outcomes Research (CORE) Diabetes Model, calibrated to baseline patient characteristics from a short-term, randomized, controlled trial of liraglutide and glimepiride monotherapies (Liraglutide Effect and Action in Diabetes [LEAD]-3 trial) and using data from long-term outcomes studies., Setting: Simulated routine clinical practice., Patients: Seven hundred forty-six patients with type 2 diabetes who participated in the LEAD-3 trial, and three hypothetical cohorts of 5000 patients each that were based on the baseline characteristics of the patients in the LEAD-3 trial. The patients in the LEAD-3 trial were randomly assigned to monotherapy with liraglutide 1.2 mg/day (251 patients), liraglutide 1.8 mg/day (247 patients), or glimepiride 8 mg/day (248 patients)., Measurements and Main Results: The impact of the three treatments for type 2 diabetes on survival and cumulative incidence of cardiovascular, ocular, or renal events and costs were estimated at three time periods: 10, 20, and 30 years. Simulations predicted improved survival for liraglutide 1.8 and 1.2 mg at all three time points compared with glimepiride. Survival benefits were greatest after 30 years of follow-up: 16.5%, 13.6%, and 7.3%, respectively. The frequency of nonfatal renal and ocular events was lower for both liraglutide doses than for glimepiride. The rate of neuropathies leading to first or recurrent amputation was higher for glimepiride compared with both liraglutide doses. The average cumulative cost/patient was higher for glimepiride compared with liraglutide 1.2 mg and liraglutide 1.8 mg., Conclusion: With use of the CORE Diabetes Model and data from the LEAD-3 trial, long-term projected survival, diabetes complications, and costs favored liraglutide 1.2- and 1.8-mg monotherapies compared with glimepiride in the treatment of type 2 diabetes.

Purpose: Diabetes is a debilitating illness requiring lifelong management. Treatments can be varied in terms of mode of administration as well as type of agent. Unfortunately, most patient reported outcome measures currently available to assess the impact of treatment are specific to diabetes type, treatment modality or delivery systems and are designed to be either a HRQoL or treatment satisfaction measure. To address these gaps, the Treatment Related Impact Measure-Diabetes and Device measures were developed. This paper presents the item development and validation of the TRIM Diabetes/Device., Methods: Patient interviews were conducted to collect the patient perspective and ensure high content validity. Interviews were hand coded and qualitatively analyzed to identify common themes. A conceptual model of the impact of diabetes medication was developed and preliminary items for the TRIM-Diabetes/Device were generated and cognitively debriefed. Validation data was collected via an on-line survey and analyzed according to an a priori statistical analysis plan to validate the overall score as well as each domain. Item level criteria were used to reduce the preliminary item pool. Next, factor analysis to identify structural domains was performed. Reliability and validity testing was then performed., Results: One hundred and five patients were interviewed in focus groups, individual interviews and for cognitive debriefing. Five hundred seven patients participated in the validation study. Factor analysis identified seven domains: Treatment Burden, Daily Life; Diabetes Management; Psychological Health; Compliance and Device Function and Bother. Internal consistency reliability coefficients of the TRIM-Diabetes/Device ranged from 0.80 and 0.94. Test-retest reliability of the TRIM-Diabetes/Device ranged from 0.71 to 0.89. All convergent and known groups validity hypotheses were met for the TRIM-Diabetes/Device total scores and sub-scales., Conclusion: Validation is an ongoing and iterative process. These findings are the first step in that process and have shown that both the TRIM-Diabetes and the TRIM-Diabetes Device have acceptable psychometric properties. Future research is needed to continue the validation process and examine responsiveness and the validity of the TRIM-Diabetes/Device in a clinical trial population.

Background: Poor control of type 2 diabetes results in substantial long-term consequences. Studies of new diabetes treatments are rarely designed to assess mortality, complication rates and costs. We sought to estimate the long-term consequences of liraglutide and rosiglitazone both added to glimepiride., Methods: To estimate long-term clinical and economic consequences, we used the CORE diabetes model, a validated cohort model that uses epidemiologic data from long-term clinical trials to simulate morbidity, mortality and costs of diabetes. Clinical data were extracted from the LEAD-1 trial evaluating two doses (1.2 mg and 1.8 mg) of a once daily GLP-1 analog liraglutide, or rosiglitazone 4 mg, on a background of glimepiride in type 2 diabetes. CORE was calibrated to the LEAD-1 baseline patient characteristics. Survival, cumulative incidence of cardiovascular, ocular and renal events and healthcare costs were estimated over three periods: 10, 20 and 30 years., Results: In a hypothetical cohort of 5000 patients per treatment followed for 30 years, liraglutide 1.2 mg and 1.8 mg had higher survival rates compared to the group treated with rosiglitazone (15.0% and 16.0% vs. 12.6% after 30 years), and fewer cardiovascular, renal, and ocular events. Cardiovascular death rates after 30 years were 69.7%, 68.4% and 72.5%, for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively. First and recurrent amputations were lower in the rosiglitazone group, probably due to a 'survival paradox' in the liraglutide arms (number of events: 565, 529, and 507, respectively). Overall cumulative costs per patient, were lower in both liraglutide groups compared to rosiglitazone (US$38,963, $39,239, and $40,401 for liraglutide 1.2 mg, 1.8 mg, and rosiglitazone, respectively), mainly driven by the costs of cardiovascular events in all groups., Conclusion: Using data from LEAD-1 and epidemiologic evidence from the CORE diabetes model, projected rates of mortality, diabetes complications and healthcare costs over the long term favor liraglutide plus glimepiride over rosiglitazone plus glimepiride., Trial Registration: LEAD-1 NCT00318422; LEAD-2 NCT00318461; LEAD-3 NCT 00294723; LEAD-4 NCT00333151; LEAD-5 NCT00331851; LEAD-6 NCT00518882.

Objectives: To assess the costs of severe hypoglycaemic events (SHEs) in diabetes patients in Germany, Spain and the UK., Methods: Healthcare resource use was measured by surveying 639 patients aged ≥ 16 years, receiving insulin for type 1 (n=319) or type 2 diabetes (n=320), who experienced ≥ 1 SHE in the preceding year. Patients were grouped by location of SHE treatment: group 1, community (family/domestic); group 2, community (healthcare professional); group 3, hospital. Costs were calculated from published unit costs applied to estimated resource use. Costs per SHE were derived from patient numbers per subgroup. Weighted average costs were derived using a prevalence database., Results: Hospital treatment was a major cost in all countries. In Germany and Spain, costs per SHE for type 1 patients differed from those for type 2 patients in each group. Average SHE treatment costs were higher for patients with type 2 diabetes (Germany, €533; Spain, €691; UK, €537) than type 1 diabetes patients (€441, €577 and €236, respectively). Telephone calls, visits to doctors, blood glucose monitoring and patient education contributed substantially to costs for non-hospitalised patients., Conclusions: Treatment of SHEs adds significantly to healthcare costs. Average costs were lower for type 1 than for insulin-treated type 2 diabetes, in all three countries.

Objective: To estimate the costs to treat oesophageal variceal bleeding in patients with cirrhosis in France from a hospital perspective., Methods: A model was developed to present the current treatment pathway of variceal bleeding in France covering 42 days from hospital admission. Input of the model was based on interviews with 10 hepatogastroenterologists geographically spread throughout France. A validated questionnaire was used to collect medical resource-use of the treated patients separated for patients suffering from Child-Pugh class A, B and C liver disease., Results: Average hospital treatment cost of patients requiring only initial management to stop the bleeding was euro 9906. Costs of patients in whom initial treatment was not successful averaged euro 23,113 and euro 29,406 for patients requiring respectively one or two additional procedures to control the bleeding. On average, the hospital incurred euro 11,134, euro 12,698 and euro 14,168 for class A, B and C patients, respectively., Conclusions: Management of variceal bleeding is very costly compared with other digestive diseases. In particular, additional treatment needed because of failure to control bleeding or early rebleeding makes the management expensive. The severity of the underlying liver disease has a great impact on treatment outcome, leading to higher treatment costs for class C patients than less affected patients.