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Learn more: PMC Disclaimer | PMC Copyright Notice Diabetes Obes Metab . 2026 Feb 24;28(5):4100–4111. doi: 10.1111/dom.70599 Search in PMC Search in PubMed View in NLM Catalog Add to search Pre‐Treatment Concerns and Their Association With Functioning and Well‐Being During Incretin‐Based Therapy: A Cross‐Sectional Study Ali Kapan Ali Kapan 1 Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Vienna, Austria Find articles by Ali Kapan 1, ✉ , Tobias Brandl Tobias Brandl 1 Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Vienna, Austria Find articles by Tobias Brandl 1 , Thomas Waldhör Thomas Waldhör 2 Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria Find articles by Thomas Waldhör 2 , Othmar Moser Othmar Moser 3 Exercise Physiology, Training & Training Therapy Research Group, Institute of Human Movement Science, Sport and Health, University of Graz, Graz, Austria 4 Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria Find articles by Othmar Moser 3, 4 , Richard Felsinger Richard Felsinger 1 Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Vienna, Austria Find articles by Richard Felsinger 1 Author information Article notes Copyright and License information 1 Department of Social and Preventive Medicine, Center for Public Health, Medical University of Vienna, Vienna, Austria 2 Department of Epidemiology, Center for Public Health, Medical University of Vienna, Vienna, Austria 3 Exercise Physiology, Training & Training Therapy Research Group, Institute of Human Movement Science, Sport and Health, University of Graz, Graz, Austria 4 Division of Endocrinology and Diabetology, Department of Internal Medicine, Medical University of Graz, Graz, Austria * Correspondence: Ali Kapan ( [email protected] ) ✉ Corresponding author. Revised 2026 Feb 11; Received 2025 Dec 17; Accepted 2026 Feb 14; Issue date 2026 May. © 2026 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. PMC Copyright notice PMCID: PMC13071259 PMID: 41733056 ABSTRACT Aim This study aims to examine weight‐loss history and pre‐treatment concerns, and their associations with current functioning and well‐being in adults undergoing incretin‐based pharmacotherapy for obesity. Materials and Methods This cross‐sectional study analysed 411 adults treated with three different incretin‐based medications. Demographics, previous weight‐loss interventions, barriers to earlier attempts, reasons for initiating incretin therapy, treatment characteristics and Treatment‐Related Impact Measure for Weight (TRIM‐Weight) total scores were assessed. Associations between specific pre‐treatment concerns and functioning and well‐being were analysed using univariate models and a multivariable regression model that adjusted for treatment related variables. Results Participants had a median age of 39 years (IQR 33–47), 79.1% were women, and the median BMI was 36.3 kg/m 2 (IQR 32.2–42.3). The median TRIM‐Weight total score was 68.2 (IQR 64.0–73.4). Most respondents (95.1%) had attempted weight loss, typically through combined diet and physical activity (71.8%), intermittent fasting (69.6%) and digital tracking tools (65.7%). In fully adjusted models, fear of side effects ( β = −3.53, 95% CI −4.05 to −3.01), concerns about cost ( β = −0.92, 95% CI −1.37 to −0.47) and injection anxiety ( β = −0.67, 95% CI −1.16 to −0.18) were associated with lower functioning and well‐being. Doubts regarding effectiveness showed a small positive association ( β = 0.61, 95% CI 0.03–1.19). Conclusion Among retrospectively reported pre‐treatment concerns, fear of side effects, treatment costs and injection anxiety were most strongly associated with lower functioning and well‐being, whereas moral or psychosocial concerns showed no independent associations after multivariable adjustment. Keywords: incretin therapy, patient reported outcome, semaglutide, tirzepatide obesity, well‐being 1. Background Incretin‐based pharmacotherapies, including glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) and dual glucose‐dependent insulinotropic polypeptide/glucagon‐like peptide‐1 receptor agonists (GIP/GLP‐1 RAs), have become a key part of modern type 2 diabetes and obesity treatment in recent years [ 1 ]. Studies have shown that agents such as semaglutide and tirzepatide lead to significant weight loss [ 2 ]. They also enhance metabolic health by improving glycaemic control, blood pressure and lipid profiles, while decreasing the risk of major adverse cardiovascular events by as much as 20% [ 2 , 3 , 4 , 5 ]. Alongside these metabolic benefits, growing evidence demonstrates improvements in patient‐reported outcomes, with increasing scientific interest in treatment expectations, subjective experiences and weight‐related functioning and well‐being during therapy [ 6 ]. Understanding the patient journey towards incretin therapy initiation is crucial for contextualising treatment outcomes. Clinical trials show that 95% of participants had previously attempted weight loss through various interventions, suggesting that incretin therapy is rarely used as a first‐line approach [ 7 , 8 ]. However, detailed characterisation of these prior experiences remains largely absent from the literature, as most clinical and real‐world studies of incretin‐based pharmacotherapy report little or no systematic data on the number of weight‐loss attempts, the specific modalities previously used (such as structured dietary programmes, behavioural counselling or digital health tools), or patients' perceived effectiveness of these strategies, which are seldom documented in real‐world studies conducted before initiating incretin therapy [ 6 , 9 , 10 ]. Beyond these anamnestic considerations, real‐world implementation reveals considerable contemporary challenges. Discontinuation rates are substantial, with approximately one‐third to one‐half of patients discontinuing incretin therapy within the first year, and nearly two‐thirds within 2 years [ 11 , 12 ], while high annual drug costs of approximately USD 12 700 for tirzepatide and USD 16 200 for semaglutide at current list prices pose significant access barriers for patients without insurance coverage [ 13 , 14 , 15 ]. Furthermore, the distinctive nature of these therapies introduces treatment‐specific issues not faced with traditional weight management approaches. Emerging evidence suggests that patients experience distinct psychological dimensions when starting incretin therapy, including injection anxiety, social stigmatisation related to medication‐assisted weight loss and moral concerns about ‘cheating’ versus achieving weight loss through personal effort alone [ 16 ]. Despite extensive documentation of the metabolic efficacy of incretin therapies, it remains unclear whether pre‐treatment concerns are associated with the functioning and well‐being patients report during ongoing treatment. This cross‐sectional study aimed to characterise previous weight‐management attempts and their perceived effectiveness, identify pre‐treatment concerns about initiating incretin therapy and explore associations between these retrospectively reported concerns and current weight‐related functioning and well‐being in adults receiving incretin‐based treatment for obesity. 2. Methods This cross‐sectional study is a secondary analysis of a dataset previously reported. The procedures for the original data collection are detailed elsewhere [ 4 ]. In brief, participants were recruited through targeted invitations shared in online peer‐support groups and across several social media platforms (Facebook, Instagram, WhatsApp and X, formerly Twitter). Data were collected between 13 January and 28 February 2025 using the SoSci Survey platform ( https://www.soscisurvey.de ), which included technical measures to prevent duplicate entries and employed reCAPTCHA verification to block automated responses. The study complied with the principles of the Declaration of Helsinki and received ethical approval from the Ethics Committee of the Medical University of Vienna (approval number 2506/2024). All participants gave electronic informed consent before enrolment. The survey instrument was designed following established standards for online research and adhered to the CHERRIES checklist to ensure methodological rigour, data protection and participant confidentiality. 2.1. Eligibility Criteria Participants were required to be undergoing active treatment with a GLP‐1 receptor agonist or a dual GIP/GLP‐1 receptor agonist for weight management, with a minimum treatment duration of 3 months at the time of survey completion. Additional inclusion criteria included being at least 18 years old and having a body mass index (BMI) at the start of treatment of ≥ 30 kg/m 2 , or a BMI between 27.0 and 29.9 kg/m 2 combined with at least one weight‐related comorbidity (e.g., prediabetes, type 2 diabetes, hypertension, dyslipidaemia, obstructive sleep apnoea or cardiovascular disease). As the questionnaire was designed to target an international English‐speaking audience, participants had to complete the survey in English. 2.2. Survey Content 2.2.1. Sociodemographic and Clinical Characteristics Data collected included age, sex, marital status, educational level, employment status and monthly net income. Anthropometric parameters comprised self‐reported height, current body weight and baseline weight at the start of treatment, from which BMI was calculated at both time points. Additionally, the incretin agent used (semaglutide 1.0 mg, semaglutide 2.4 mg or tirzepatide), treatment duration in weeks and the speciality of the prescribing physician were recorded. 2.3. Treatment‐Related Impact Measure for Weight To evaluate the perceived impact of pharmacological weight management, the Treatment‐Related Impact Measure for Weight (TRIM‐Weight) was used. This validated patient‐reported outcome instrument assesses treatment experiences across five domains: weight management, daily life, treatment burden, side effects and psychological well‐being. Together, these domains capture how therapy affects everyday functioning and overall well‐being. Scores are transformed to a standardised 0–100 scale, with higher scores indicating more favourable outcomes. Use of the TRIM‐Weight instrument was authorised by Mapi Research Trust via the ePROVIDE platform and applied in accordance with licensing requirements [ 17 ]. 2.4. Previous Attempts in Different Weight Loss Interventions Participants indicated whether they had previously attempted weight loss and counted their number of attempts. Using multiple selections, they rated the subjective success of the following interventions on a four‐point Likert scale (1 = not at all successful, 2 = slightly successful, 3 = moderately successful, 4 = very successful): low‐calorie diets, low‐carbohydrate diets (e.g., keto, Atkins), low‐fat diets, intermittent fasting (e.g., 16:8, 5:2), physical activity alone (e.g., gym workouts, yoga and walking), combined diet and physical activity, apps or digital tools for tracking nutrition and activity, behavioural therapy or counselling and herbal or alternative medicine approaches. These intervention categories are based on evidence from systematic reviews, which consistently describe these methods as the most commonly practised and researched approaches to intentional weight loss in adults [ 18 , 19 , 20 , 21 ]. 2.5. Barriers to Previous Weight Loss Efforts Participants could select more than one response option. Barriers to previous weight loss efforts were categorised into several groups: physiological factors including food noise (defined as persistent and intrusive thoughts about food and heightened reactivity to food cues [ 22 ]), behavioural aspects such as lack of motivation, consistency and emotional eating; structural constraints including time limitations, family responsibilities, financial challenges and irregular eating patterns; perceived impracticality or unfeasibility of certain approaches in daily life; and lack of professional advice or support. These categories are based on empirical studies that indicate barriers to sustained weight loss tend to cluster around physiological regulation, self‐regulation, environmental pressures and method‐related limitations [ 23 ]. 2.6. Concerns and Barriers Before Starting Incretin Therapy At the time of the survey, participants were asked whether they had experienced any fears or barriers before starting their incretin therapy. The questionnaire covered all common concerns described in existing literature and clinical practice: worries about cost, fear of social reactions, concern about stigma, fear of becoming dependent on the medication, doubts regarding treatment effectiveness, fear of injections and possible side effects and the perception that using medication for weight loss might be seen as ‘cheating’ [ 16 ]. Response options used a five‐point Likert scale (0 = not at all concerned, 1 = slightly concerned, 2 = moderately concerned, 3 = highly concerned, 4 = very highly concerned). These items enabled a thorough assessment of the key emotional, social and practical barriers individuals might have faced when considering initiating incretin therapy. 2.7. Reasons for Initiating Incretin Therapy Motivations for initiating incretin therapy were evaluated using multiple‐choice questions, with participants allowed to select more than one response option. These included aesthetic factors (such as improved physical appearance), health‐related objectives (such as better overall health, disease management or reduced pain and mobility limitations), psychosocial factors (including enhanced self‐esteem and emotional well‐being), functional measures (such as fitness, mobility and energy levels) and physician recommendations. These categories mirror motivational patterns identified in existing weight‐management research [ 16 ]. 2.8. Statistics To assess distributional assumptions, all continuous variables were evaluated using the Shapiro–Wilk test and visual inspection of histograms. Normally distributed data were summarised as mean ± standard deviation, whereas non‐normally distributed variables were reported as median and quartiles (IQR). Categorical variables were presented as absolute frequencies and percentages. Descriptive analyses were additionally performed for barriers to previous weight‐loss attempts, the frequency of past attempts and motivations for initiating incretin therapy. To examine the relationship between pre‐treatment concerns and current weight‐related functioning and well‐being, a linear regression analysis was performed using the TRIM‐Weight Total Score at the time of the survey as the dependent variable. Variables related to concerns and barriers before starting incretin therapy were used as independent variables. Initially, univariate regression models were calculated for each concern variable, with adjustments for age and sex. Subsequently, all concern variables were entered simultaneously into a multivariable regression model. This multivariable model was further adjusted for the type of incretin medication used, treatment duration, administered dose, cost coverage status, change in BMI (ΔBMI) and the sum of self‐reported side effects. To address potential recall bias in individuals currently experiencing side effects, sensitivity analyses were performed using an aggregated measure of current side‐effect burden, defined as the sum of self‐reported side effects. The fully adjusted multivariable model was re‐estimated using median‐based dichotomisation of side‐effect burden (≤ 2 vs. ≥ 3 side effects); an alternative cut‐off (≤ 1 vs. ≥ 2 side effects) was examined to assess robustness. All covariates were retained across models. Multicollinearity was assessed using tolerance values and variance inflation factors, all of which were below 1.12, indicating excellent independence among predictors. Model performance was evaluated using the adjusted R 2 statistic, and statistical significance was defined as a two‐sided p ‐value less than 0.05. p ‐values were not adjusted for multiple testing and were interpreted explorative only. All statistical analyses were performed using SPSS version 28.0 (IBM Corp., Armonk, NY). Figures were generated with GraphPad Prism 10 for Windows, version 10.2.2 (341). 3. Results A total of 676 individuals initiated the questionnaire. Of these, 411 participants (60.8%) completed the full survey and were included in the analyses. The remaining 265 individuals (39.2%) discontinued at various stages during the baseline assessment (ranging from eligibility screening to sociodemographic and anthropometric questions). Among these non‐completers, the median age was 37 years (IQR 28–50), the median baseline BMI was 34.4 kg/m 2 (IQR 31.4–39.6) and 72% were female. These participants did not reach the outcome measures section (TRIM‐Weight scores, pre‐treatment concerns, side effects or treatment experiences); therefore, they were excluded from all analyses. Participants mainly came from the United States ( n = 111; 27%), the United Kingdom ( n = 96; 23%) and Germany ( n = 80; 20%). Other countries of origin included Canada ( n = 36; 9%), Australia ( n = 26; 6%), Spain ( n = 18; 4%) and Portugal ( n = 6; 2%). Additionally, 38 individuals (9%) were from various other European countries. The median age of the sample was 39 years (IQR: 33–47), with little difference between women (39 years, IQR: 31–47) and men (40 years, IQR: 34–48; Table 1 ). Table 2 summarises incretin therapy characteristics and treatment outcomes. The most frequently used medication was semaglutide 2.4 mg/week (217 participants; 52.8%), followed by semaglutide 1.0 mg/week (148; 36.0%) and tirzepatide (46; 11.2%). Baseline BMI was higher in women (median 37.0, IQR: 33.5–42.6) than in men (33.6, IQR: 30.5–38.8). Median BMI reduction was slightly greater in women (ΔBMI 6.5, IQR: 4.4–7.9) compared with men (4.8, IQR: 3.2–6.1). Overall, 50 participants (12.2%) had full cost coverage for incretin therapy (all of them having type 2 diabetes), 109 (26.5%) had partial coverage and 252 (61.3%) had no coverage. Nearly all participants (391; 95.1%) had previously attempted weight loss, with a median of four attempts (IQR: 2–6). TRIM‐Weight total scores were similar between women (mean 68.0 ± 7.1) and men (68.6 ± 7.1), with comparable subscale scores across sexes. TABLE 1. Sociodemographic, clinical and lifestyle characteristics of participants ( n = 411). Variables All ( n = 411) Female ( n = 295) Male ( n = 116) Age (years), median (IQR) 39 (33–47) 39 (31–47) 40 (34–48) Marital status, n (%) Married 73 (17.8) 54 (18.3) 19 (16.4) Divorced 73 (17.8) 46 (15.6) 27 (23.3) Single 125 (30.4) 100 (33.9) 25 (21.6) Widowed 1 (0.2) 1 (0.3) 0 (0) In a relationship 139 (33.8) 94 (31.9) 45 (38.8) Income in Euro, n (%) < 500 14 (3.4) 9 (3.1) 5 (4.3) 500 to < 1000 20 (4.9) 14 (4.7) 6 (5.2) 1000 to < 1500 42 (10.2) 32 (10.8) 10 (8.6) 1500 to < 2000 86 (20.9) 59 (20.0) 27 (23.3) 2000 to < 3000 183 (44.5) 132 (44.7) 51 (44.0) 3000 to < 4000 24 (5.8) 19 (6.4) 5 (4.3) 4000 to < 5000 4 (1.0) 4 (1.4) 0 (0) ≥ 5000 12 (2.9) 6 (2.0) 6 (5.2) Prefer not to answer 26 (6.3) 20 (6.8) 6 (5.2) Employment status, n (%) Training/apprenticeship 74 (18.0) 56 (19.0) 18 (15.5) University student 88 (21.4) 61 (20.7) 27 (23.3) Employee 183 (44.5) 133 (45.1) 50 (43.1) Self‐employed 60 (14.6) 40 (13.6) 20 (17.2) Prefer not to answer 6 (1.5) 5 (1.7) 1 (0.9) Comorbidities, n (%) Hypertension 140 (34.1) 125 (42.4) 15 (12.9) Sleep apnea 39 (9.5) 24 (8.1) 15 (12.9) Dyslipidemia 141 (34.3) 115 (39.0) 26 (22.4) NAFLD 33 (8.0) 19 (6.4) 14 (12.1) Stroke 27 (6.6) 17 (5.8) 10 (8.6) Type 2 diabetes 146 (35.5) 104 (35.3) 42 (36.2) Knee osteoarthritis 80 (19.5) 47 (15.9) 33 (28.4) Open in a new tab Note : Values are presented as n (%) for categorical variables and as median and interquartile range (IQR) for continuous variables. Abbreviation: NAFLD, non‐alcoholic fatty liver disease. TABLE 2. Incretin therapy characteristics and treatment outcomes. Variables All ( n = 411) Female ( n = 295) Male ( n = 116) Incretin therapy, n (%) Semaglutide 2.4 mg/week 217 (52.8) 155 (52.5) 62 (53.4) Semaglutide 1.0 mg/week 148 (36.0) 114 (38.6) 34 (29.3) Tirzepatide 10 mg/week 31 (7.6) 14 (4.7) 17 (14.7) Tirzepatide 12.5 mg/week 15 (3.6) 12 (4.2) 3 (2.6) Duration of therapy (weeks), median (IQR) 43 (30–60) 49 (37–62) 32 (24–45) Anthropometric measurements Height (cm), median (IQR) 169 (164–174) 166 (162–170) 177 (174–181) Weight (kg), median (IQR) 105.5 (92.5–120.0) 102.5 (90.6–118.6) 108.3 (98.0–122.1) BMI baseline, median (IQR) 36.4 (32.6–41.4) 37.0 (33.5–42.6) 33.6 (30.5–38.8) BMI follow‐up, median (IQR) 30.9 (27.6–35.2) 31.2 (28.1–35.7) 28.9 (27.0–33.9) Delta BMI, median (IQR) 6.0 (4.0–7.4) 6.5 (4.4–7.9) 4.8 (3.2–6.1) Weight loss (kg/month), median (IQR) 1.5 (1.3–1.9) 1.4 (1.2–1.7) 1.8 (1.5–2.3) Cost coverage for incretin therapy, n (%) Yes 50 (12.2) 39 (13.2) 11 (9.5) Partially 109 (26.5) 84 (28.5) 25 (21.6) No 252 (61.3) 172 (58.3) 80 (69.0) Adverse events during incretin therapy, n (%) Nausea 147 (35.8) 90 (30.5) 57 (49.1) Constipation 112 (27.3) 87 (29.5) 25 (21.6) Diarrhoea 109 (26.5) 83 (28.1) 26 (22.4) Vomiting 107 (26.0) 76 (25.8) 31 (26.7) Eructation 89 (21.7) 61 (20.7) 28 (24.1) depressed mood 80 (19.5) 66 (22.4) 14 (12.1) Fatigue 64 (15.6) 36 (12.2) 28 (24.1) Nasopharyngitis 63 (15.3) 46 (15.6) 17 (14.7) Injection‐site hematoma 51 (12.4) 33 (11.2) 18 (15.5) Dizziness 49 (11.9) 25 (8.5) 24 (20.7) Abdominal pain 48 (11.7) 29 (9.8) 19 (16.4) Number of adverse events during incretin therapy, median (IQR) 2 (1–4) 2 (1–3) 3 (2–4) Have you tried any weight loss diets? n (%) Yes 391 (95.1) 279 (94.6) 112 (96.6) No 20 (4.9) 16 (5.4) 4 (3.4) Number of previous attempts, median (IQR) 4 (2–6) 4 (2–6) 4 (3–6) TRIM‐Weight scores (0–100), mean ± SD TRIM‐Weight total score 68.2 ± 7.1 68.0 ± 7.1 68.6 ± 7.1 Daily life Weight management 67.2 ± 17.2 65.8 ± 16.8 70.6 ± 17.7 Treatment burden 59.7 ± 17.5 59.7 ± 17.4 59.9 ± 17.5 Experience of side effects 44.8 ± 13.3 45.1 ± 12.8 43.9 ± 14.4 Psychological health 81.6 ± 16.7 81.4 ± 16.8 82.4 ± 16.5 Open in a new tab Note : Values are presented as n (%) for categorical variables; medians with interquartile range (IQR) for non‐normally distributed continuous variables; and means with standard deviations for TRIM‐Weight scores. Abbreviations: ΔBMI (Delta BMI), change in BMI, calculated as baseline BMI minus follow‐up BMI; BMI, body mass index (kg/m 2 ); TRIM‐Weight, Treatment‐Related Impact Measure for Weight. Table 3 presents associations between retrospectively reported pre‐treatment concerns and current TRIM‐Weight scores. In the fully adjusted model, higher levels of concern were associated with lower weight‐related functioning and well‐being. The strongest association was observed for fear of side effects, where each one‐point increase in concern was associated with a 3.5‐point lower TRIM‐Weight total score ( β = −3.53; 95% CI: −4.05 to −3.01; p < 0.001). Smaller negative associations were found for concerns about treatment costs ( β = −0.92; 95% CI: −1.37 to −0.47; p < 0.001), fear of injections ( β = −0.67; 95% CI: −1.16 to −0.18; p = 0.007) and concerns about social reactions ( β = −0.61; 95% CI: −1.18 to −0.04; p = 0.036). In contrast, doubts about effectiveness showed a small positive association with TRIM‐Weight scores ( β = 0.61; 95% CI: 0.03–1.19; p = 0.039). Concerns related to cheating, dependence and stigma were not statistically significantly associated with TRIM‐Weight scores after multivariable adjustment. Sensitivity analyses using an aggregated measure of current side‐effect burden yielded consistent results. Re‐estimation of the fully adjusted multivariable model using median‐based dichotomisation of side‐effect burden (≤ 2 vs. ≥ 3 side effects), as well as an alternative cut‐off (≤ 1 vs. ≥ 2 side effects), resulted in virtually identical effect estimates for fear of side effects ( β ≈ −3.6), with overlapping confidence intervals across models. These findings indicate that the association between fear of side effects and lower TRIM‐Weight scores was robust to different operationalisations of current side‐effect burden. TABLE 3. Associations of patient concerns about initiating incretin therapy with the TRIM‐Weight total score. TRIM‐Weight total score Variables Univariate models Multivariable model β (95% CI) R 2 p β (95% CI) R 2 p Fear of side effects −3.88 (−4.42, −3.34) 0.12 < 0.001 −3.53 (−4.05, −3.01) 0.14 < 0.001 Concern about cost −1.58 (−2.11, −1.05) 0.09 < 0.001 −0.92 (−1.37, −0.47) < 0.001 Fear of injections −1.15 (−1.78, −0.52) 0.03 < 0.001 −0.67 (−1.16, −0.18) 0.007 Feeling of cheating −1.04 (−1.76, −0.32) 0.02 0.004 −0.29 (−0.88, 0.30) 0.331 Concern about dependence −0.98 (−1.68, −0.28) 0.02 0.006 −0.31 (−0.86, 0.24) 0.271 Doubt about effectiveness 0.88 (0.06, 1.70) 0.01 0.034 0.61 (0.03, 1.19) 0.039 Concern social reaction −0.73 (−1.45, −0.01) 0.01 0.047 −0.61 (−1.18, −0.04) 0.036 Concern about stigma −0.19 (−0.71, 0.33) 0.02 0.468 0.18 (−0.36, 0.72) 0.515 Open in a new tab Note : Univariable models were calculated, each adjusted for age and sex. Subsequently, a multivariable regression model included all concern variables simultaneously and was additionally adjusted for incretin medication type, treatment duration, medication dose, cost coverage status, BMI change (ΔBMI) and number of reported side effects. p ‐values were not adjusted for multiple testing and should be interpreted as exploratory. Abbreviation: TRIM‐Weight, Treatment‐Related Impact Measure for Weight. Figure 1 shows that the most common strategy for previous weight‐management attempts was combining diet and physical activity, used by 295 participants. Among these participants, 34.2% rated this approach as moderately successful and 33.6% as very successful. Intermittent fasting was reported by 286 participants, with 39.2% rating it as moderately successful and 25.5% as very successful. Digital apps for tracking nutrition or physical activity were used by 270 participants; most rated their success as moderately successful (40.4%) or slightly successful (31.5%). A low‐calorie diet was adopted by 247 participants, with 44.9% reporting slight success and 35.6% moderate success. Physical activity alone was used by 213 participants; 47.9% rated it as moderately successful and 16.4% as very successful. FIGURE 1. Open in a new tab Previous weight loss interventions. Percentages reflect participants' perceived success of previous weight‐management attempts. Multiple responses were allowed, and sample sizes ( n ) indicate the number of participants who reported using each method. Therefore, the total number of answers does not add up to the full sample size. Figure 2 summarises participants' reasons for initiating incretin therapy (panel a) and perceived barriers to previous unsuccessful weight‐loss attempts (panel b). Percentages indicate the proportion of participants endorsing each item; multiple responses were allowed. As shown in panel (a), the most frequently reported reasons for initiating incretin therapy were improving appearance (82.7%) and improving overall health (79.6%). Nearly half of participants reported improving self‐esteem or personal satisfaction (49.6%), followed by improving fitness, mobility, or energy (46.2%). Panel (b) shows that the most common barriers to previous unsuccessful weight‐loss attempts were social or environmental factors, such as lack of time or family responsibilities (55.2%), and an unrealistic or unsustainable approach (54.7%). Food noise (48.4%) and lack of motivation or consistency (38.4%) were also frequently reported. FIGURE 2. Open in a new tab Reasons for initiating incretin therapy and barriers to previous weight‐loss attempts. Percentages represent the proportion of participants selecting each reason/barrier. Multiple responses were allowed. Panel (a) shows self‐reported reasons for initiating incretin therapy. Panel (b) shows perceived barriers contributing to unsuccessful previous weight‐loss attempts. Sample sizes ( n ) correspond to the number of participants endorsing each item. As shown in Figure 3 , fear of side effects was the most frequently reported concern, with 30.9% of participants reporting moderate concern, 38.4% high concern and 7.5% very high concern. Concerns about treatment costs were also common, with 17.5% reporting moderate concern, 35.8% high concern and 15.8% very high concern. Fear of injections was reported by 33.1% of participants at a moderate level, 16.5% at a high level and 6.8% at a very high level. Concerns about dependence on medication were also frequently reported, with a substantial proportion of participants indicating moderate to very high concern. FIGURE 3. Open in a new tab Concerns and barriers about initiating incretin therapy. The figure displays participants' concerns about initiating incretin therapy, assessed using a five‐point Likert scale. Each item was rated once per participant with the following response options: 0 = not at all concerned, 1 = slightly concerned, 2 = moderately concerned, 3 = highly concerned and 4 = very highly concerned. Percentages represent the proportion of respondents selecting each category for each concern. 4. Discussion This cross‐sectional study of 411 adults receiving incretin‐based pharmacotherapy for obesity and type 2 diabetes provides new insights into weight‐management experiences before treatment and into the associations between retrospectively reported pre‐treatment concerns and current weight‐related functioning and well‐being. The findings complement existing evidence by incorporating a patient‐centred psychosocial perspective into research that has predominantly focused on the metabolic outcomes of incretin therapies. The patterns of previous weight‐management attempts show that combined diet and exercise approaches were the most commonly used, with 34.2% of participants rating them as moderately successful and 33.6% as very successful [ 19 , 24 ]. Digital tools and apps were rated as moderately successful by 40.4% and very successful by 12.6%, while intermittent fasting was rated as moderately successful by 39.2% and very successful by 25.5%, reflecting the perceived effectiveness of contemporary lifestyle‐based strategies. However, in line with previous findings showing mixed and generally modest long‐term success for these approaches [ 25 , 26 ], most participants' ratings in our study were heterogeneous, with substantial proportions reporting moderate to very high success, while others reported only slight success. The shift from lifestyle‐based methods to pharmacotherapy in this cohort can be viewed alongside growing real‐world evidence on incretin‐based treatments. Observational studies showed that individuals who remain on GLP‐1 receptor agonists for 6–12 months achieve median weight losses of 9.4%–14.4% [ 27 ], while comparative real‐world analyses suggest that tirzepatide is more effective than semaglutide (5.3% vs. 2.7% over 6 months) [ 28 ]. Although these reductions are clinically meaningful, they are lower than those reported in randomised controlled trials, where semaglutide 2.4 mg results in average losses of 15%–17% and tirzepatide 15 mg up to 20%–21% of initial weight [ 29 , 30 ]. This disparity between efficacy and effectiveness likely stems from differences in patient selection, treatment support and adherence to routine‐care [ 31 ]. Further barriers to previous weight loss attempts, such as unrealistic or unsustainable approaches, social or environmental pressures, food noise and emotional eating (Figure 2b ), closely resemble patterns described in qualitative and quantitative studies of weight‐management challenges [ 23 ]. These barriers may be related to why many individuals ultimately consider pharmacotherapy after multiple unsuccessful attempts. The motivations that participants reported for initiating incretin therapy (Figure 2a ) reflect a multidimensional decision‐making process and align with patterns described in recent real‐world studies. In our sample, appearance (82.7%) and overall health (79.6%) were the primary motivators, followed by improvements in self‐esteem, mobility and mood. Similar findings were reported by Naveed et al. [ 16 ], who observed that aesthetic goals, general health improvement and psychological well‐being were the main drivers for GLP‐1 therapy initiation among 1659 adults managed in a virtual clinical setting. The comparatively low proportion of participants in our sample who reported physician recommendation (22.1%) as one of the drivers for initiating incretin therapy is noteworthy. A similar pattern has been seen in recent community research. In a large UK cross‐sectional survey of 1297 adults, only 9% of respondents said they first learned about GLP‐1 receptor agonists from healthcare providers, whereas news media (60.1%) and social media (50.3%) were the main initial sources of information [ 32 ]. These findings suggest that public awareness of incretin‐based therapies is increasingly influenced by non‐clinical sources. Furthermore, qualitative research suggests that the substantial rise in demand for incretin therapies has placed considerable pressure on primary care providers, who face the dual challenge of meeting patient expectations while adhering to clinical guidelines and dealing with limited access to these medications [ 33 ]. This tension may result in patients increasingly taking active roles in exploring and requesting pharmacological options, rather than treatment initiation being primarily driven by doctor recommendation or medical advice. Although public reporting and media attention surrounding GLP‐1–based therapies have increased markedly [ 34 ], current studies show that the actual initiation and ongoing use of incretin pharmacotherapy are influenced by a range of patient‐centred concerns. Large community surveys indicate that worries about safety, side effects and affordability are the main barriers to considering GLP‐1 receptor agonists, and only a minority of individuals learn about these treatments from healthcare professionals initially [ 32 ]. Complementary findings from qualitative studies reveal that injection anxiety, stigma, shame and fears of being perceived as ‘cheating’ are common hesitations before starting treatment [ 16 ]. Further research on anti‐obesity pharmacotherapy also highlights concerns about dependency, weight regain after discontinuation and negative social judgement [ 35 ]. In addition to the concerns identified in the present study, the historical context of incretin‐based therapies should be considered. These medications were originally developed and introduced as treatments for type 2 diabetes, and their subsequent use for weight management may shape patient perceptions, particularly among individuals without diabetes. Previous research suggests that this dual indication may contribute to concerns regarding treatment appropriateness, stigma and perceived disease severity, as these therapies may remain associated with more severe metabolic illness in public and patient discourse [ 6 , 36 ]. The pattern observed in our cohort aligns with these reports. The strongest associations with lower weight‐related functioning and well‐being were fear of side effects and concerns about treatment costs, followed by fear of injections and anticipated social reactions. These concerns remained significant even after adjusting for clinical factors, showing their relevance for patients currently in treatment. When interpreting the magnitude of these associations, it should be noted that no minimally important difference has been established for the TRIM‐Weight instrument. The total score ranges from 0 to 100, with a standard deviation of approximately 7 points in the present sample. Against this background, the observed β coefficients likely reflect small‐to‐moderate group‐level differences. The clinical relevance for individual patients cannot be determined and warrants further investigation. Furthermore, although concerns about ‘cheating’ and dependence were initially associated with poorer outcomes, these effects were no longer significant in the multivariable model, indicating that their impact is mainly explained by more dominant concerns or treatment factors like duration, dosage, or side effects. Lastly, doubts about effectiveness showed a small positive association with weight‐related functioning and well‐being. This finding is consistent with previous research [ 6 ], suggesting that individuals who initially expressed scepticism may later perceive treatment experiences more positively; however, the association was small and only marginally statistically significant, and should therefore be interpreted cautiously. Taken together, these findings suggest that practical and treatment‐related concerns such as side effects, cost and injections are more closely associated with current weight‐related functioning and well‐being than more abstract emotional or psychosocial reservations. Several limitations should be considered when interpreting the findings of this study. First, the cross‐sectional design does not allow conclusions about temporal or causal relationships between pre‐treatment concerns and current weight‐related functioning and well‐being. Second, all variables including previous weight‐loss attempts, perceived success and pre‐treatment concerns were assessed retrospectively and are therefore subject to recall bias. Participants' current treatment experiences, particularly side effects and financial burden, may have influenced retrospective recall of pre‐treatment concerns, meaning that the direction of observed associations cannot be determined. Third, weight, height and treatment characteristics were self‐reported, which may introduce measurement inaccuracies. Fourth, recruitment via social media platforms (Facebook, Instagram, WhatsApp and X) may have introduced selection bias. The sample was predominantly female (79.1%) and likely overrepresented highly educated, digitally literate individuals with high health engagement. Although analyses were adjusted for sex, the marked sex imbalance limited the assessment of sex‐specific associations or interaction effects. Consequently, generalisability to men, individuals with lower educational attainment, or less digitally engaged populations is limited and negative treatment experiences may be underrepresented. Fifth, the substantial dropout rate (39.2%) represents an important limitation. Of the 676 individuals who initiated the survey, 265 discontinued during the baseline assessment and did not provide outcome data, restricting comparisons between completers and non‐completers to baseline characteristics. As outcome measures were unavailable for non‐completers, potential associations between discontinuation and poorer treatment experiences or lower well‐being cannot be determined, and attrition‐related selection bias cannot be excluded. Sixth, the study included only adults currently receiving incretin‐based pharmacotherapy, which may limit generalisability to individuals who discontinued treatment or have never initiated therapy. Lastly, unmeasured factors such as mental health status, support systems, or provider–patient communication and source of treatment information may have influenced both concerns and quality‐of‐life outcomes as potential confounders but were not captured in the present analysis. 5. Conclusion Nearly all adults receiving incretin therapy had previously attempted weight loss multiple times, often with limited long‐term maintenance of weight loss. Among retrospectively reported pre‐treatment concerns, fear of side effects, cost worries and injection anxiety were associated with lower weight‐related functioning and well‐being during treatment, whereas moral or psychosocial concerns showed no such associations. These findings suggest that addressing practical concerns through interventions such as anticipatory side effect guidance, cost counselling and injection training may be clinically relevant, though prospective research is needed to confirm these associations. Due to the cross‐sectional design and retrospective assessment, temporal and causal relationships remain unclear. Prospective research is needed to clarify how concerns and weight‐related functioning and well‐being evolve during incretin therapy. Author Contributions A.K. conceived and designed the study, supervised data collection, analysed the data and drafted the manuscript. O.M. and T.B. helped interpret the data and made important revisions to the manuscript. T.W. offered statistical expertise and provided critical revisions. R.F. contributed to designing the study, interpreting results and revising the manuscript critically. All authors approved the final version. Funding The authors have nothing to report. Ethics Statement This human study was carried out in accordance with the ethical standards outlined in the Declaration of Helsinki [ 37 ]. The research protocol received approval from the Ethics Committee of the Medical University of Vienna (approval no. 2506/2024). Prior to participation, all respondents provided electronic informed consent through the survey platform. Conflicts of Interest O.M. has received support for clinical trials from Sêr Cymru II COFUND Fellowship/European Union, Novo Nordisk A/S, Novo Nordisk AT, Abbott Diabetes Care, Sanofi, Dexcom, Team Novo Nordisk, SAIL, Maisels Brauerei, Medtronic AT, EFSD/EASD, Falke, BISp, perfood, Ypsomed and Sinocare. He has received speaker honoraria from Medtronic AT, Medtronic International, Eli Lilly, Novo Nordisk, Sanofi, TAD Pharma, ADA, Diatec, the Professional Association of German Internists, Dexcom, AstraZeneca, Ypsomed, Insulet, Diabetologen Hessen and Abbott. O.M. has also received travel support from Novo Nordisk A/S, Novo Nordisk AT, Novo Nordisk UK, Medtronic AT, Sanofi, EASD, OEDG and DDG. He serves on advisory boards for Sanofi, TAD Pharma, Dexcom, perfood and Medtronic. The other authors declare no conflicts of interest. 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