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Abstract 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.

Abstract 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.

Abstract 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.

Objective: The purpose of this study was to assess how the risks of glycemic stage transitions observed in clinicalpractice 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 BMI530 kg/m2) to 6.5 (BMI40 kg/m2); 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. [ABSTRACT FROM AUTHOR]

An international, 14-week phase 2b clinical trial with type 2 diabetes treated with diet or monotherapy reported improved glyceamic control with different doses of liraglutide compared to placebo. Liraglutide, a once daily GLP-1 analogue, was associated with improvements in HbA1c between 1.27% and 1.74% from baseline, compared to an increase of 0.25% with placebo. Liraglutide was also associated with reductions in BMI. The CORE Diabetes Model was used to project the long-term clinical outcomes associated with three different daily doses of liraglutide (0.65, 1.25 and 1.9 mg) versus placebo. The model simulates the progression of diabetes and its complications. Mean baseline cohort characteristics from the phase 2b trial were used in the analysis (age 55.8 years, HbA1c 7.9%-points, BMI 30.1 kg/m², duration of diabetes 6.2 years). Once the 14-week treatment effects were applied, HbA1c progression followed the trend observed in the UKPDS, for both liraglutide and placebo. Clinical outcomes were projected over a lifetime horizon and discounted at 3% annually. Compared to placebo, treatment with liraglutide was projected to improve life expectancy by 0.71, 0.84 and 0.95 life years with daily doses of 0.65 mg, 1.25 mg and 1.9 mg, respectively. Quality-adjusted life expectancy was observed to increase by 0.56, 0.66 and 0.76 quality-adjusted life years, for the respective doses versus placebo. Liraglutide was also projected to delay the development of all diabetes-related complications compared to placebo, with the onset of any complication estimated to be delayed by 0.37, 0.44 and 0.52 years with liraglutide doses of 0.65, 1.25 and 1.9 mg daily versus placebo. All three doses of liraglutide were projected to reduce the cumulative incidence of microvascular complications including peripheral vascular disease, angina, myocardial infarction and congestive heart failure compared to placebo. The results from this modeling analysis indicate that the benefits of 14 weeks of treatment with liraglutide could potentially lead to improvements in life expectancy and quality-adjusted life expectancy and a reduction in--the incidence and onset of diabetes-related complications, compared to placebo, in subjects with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The objective was to evaluate the patient reported outcomes by rating of gastrointestinal (GI) symptoms as assessed as part of a 14 weeks monotherapy study investigating three doses of liraglutide (0.65, 1.25 and 1.9 rag/day) versus placebo in patients with type 2 diabetes. In a subset of participating countries the Gastrointestinal Symptoms Rating Scale (GSRS) was completed by 81 patients. GSRS is a validated measure containing 15 items on 5 domains: diarrhoea, indigestion, constipation, abdominal pain and reflux - each rated on a 7-pt Likert scale from no discomfort (score 1) to very severe discomfort (score 7). Subjects completed the questionnaire at randomization, 2, 4, 8 and 14 weeks (end of study). The data were analyzed using Fisher's exact test by categorizing subjects with an increase or no-increase/decrease in GSRS symptom rating. All treatment groups had low average GSRS rating at randomization (range: placebo 1.3-1.6; active 1.1-1.7), and at the end of the study (range: placebo 1.0-1.2; active 1.1 - 1.6). Between liraglutide and placebo the difference in GSRS ratings was primarily seen within the first two weeks after treatment initiation (range: placebo 1.0-1.6; active 1.4-2.0) - thereafter the GSRS ratings decreased towards baseline levels. While there was a tendency towards more subjects reporting an increase in symptoms after liragiutide initiation in comparison to placebo treatment, only the reflux GSRS rating showed a significant dose-dependent response (p<0.05 for 1.25 mg and 1.90 rag). For indigestion and constipation only the 1.25 mg dose reached statistical significance (p<0.05 for both). In conclusion, while liraglutide increased the reporting of GI symptoms with a significant effect on the reflux, indigestion and constipation domains, the average GSRS ratings remained low. The reported increase in symptoms was mainly observed during the first two weeks of treatment and hereafter the symptoms returned towards baseline scores supporting that the GI side effects following liraglutide administration are transient in nature. [ABSTRACT FROM AUTHOR]