Patient Beliefs and Challenges with Using GLP-1 Receptor Agonists for Weight Loss

To be eligible for this study, participants had to meet the following criteria: age ≥ 18 years; no history of pancreatitis, type 2 diabetes, bariatric surgery, or personal/family history of MEN2 syndrome or medullary thyroid cancer; and willing to complete a semi-structured interview.

Participants were recruited using three distinct strategies. First, individuals prescribed GLP-1RA medication were identified from prescription refill requests from the Family and Community Medicine clinics. These potential participants were mailed an introductory letter describing the study, which included a URL linking to a REDCap survey containing eligibility screening and consent forms. The letter also informed recipients that they would be contacted by telephone to discuss participation. The second recruitment strategy utilized the Participant Registry for Research and Recruitment Core (PRRRCore), which distributed IRB-approved email communications (IRB# 2098619). These emails contained a brief description of the study and a link to the REDCap eligibility screening, contact information, and consent form. The third strategy involved ResearchMatch, a national health volunteer registry, through which individuals received an introductory message and a link to the REDCap forms [24]. All potential participants were contacted by telephone to answer questions and review the elements of informed consent. Once consent was obtained, participants were emailed a REDCap link to complete the study survey and a W-9 form for compensation. After survey completion, participants were contacted to schedule an interview. All enrolled participants provided informed consent in accordance with the principles set forth by the Declaration of Helsinki. The University of Missouri institutional review board (IRB #2125541) approved this study. Participants received a USD 20 e-gift card upon interview completion.

Participants completed a 30-item survey. Survey data included age (in years) grouped into four categories (<25, 25–44, 45–64, >65), sex (male, female), comorbidities (such as cardiovascular disease, depression/anxiety, back/joint pain), race (White, Black, Hispanic, another race) and annual income (<USD 40K, USD 40K–59K, USD 60K–99K, USD 100K–149K, >USD 149K). Informed by HBM constructs and the current literature on GLP-1RA usage, the remaining tailored questions explored participants' awareness and perceptions of GLP-1RAs, motivation for use, perceived concerns or barriers, prior weight loss experiences, cost and accessibility, personal health goals, physical activity assessment using International Physical Activity Questionnaire (IPAQ), Perceived Competency Scale (PCS) for weight loss (mean values: low < 4 points, moderate 4–5 points and high > 5 points) and long-term considerations of medication use. The survey was piloted before it was administered to the study participants. Descriptive analyses were conducted using SAS version 9.4 (SAS Institute Inc., Cary, NC, USA) [25].

The semi-structured interviews were organized according to the HBM constructs and prompted participants to share their experiences related to perceptions, motivations, and barriers associated with GLP-1RA medication use and weight loss (Table S1) [22]. Interviews were conducted by a team of four trained interviewers (JM, RD, SC, EM), all affiliated with the Department of Family and Community Medicine. Each interviewer had prior experience in qualitative interviewing. To avoid potential bias, any patient previously seen by RD was interviewed by a different team member. Given the limited peer-reviewed literature on this topic and the relatively homogeneous nature of this study, with a narrow focus on perceptions of GLP-1RA use, we aimed to conduct 10–20 interviews per group [26].

All interviews were audio recorded using Microsoft OneNote and/or Zoom. Transcripts were cleaned by JM, CM, and RD through a process of listening to the recordings and cross-checking the OneNote- and Zoom-generated transcripts. We employed conventional content analysis to explore responses to questions about the use of GLP-1RA medication for weight loss [27]. To ensure methodological transparency and analytic rigor, we adhered to the Consolidated Criteria for Reporting Qualitative Research (COREQ-32) [28]. Although the Health Belief Model (HBM) informed the development of the interview guide and provided a conceptual lens for interpreting findings, the coding process itself was inductive. This approach is well-suited to areas with limited prior research, allowing themes to emerge directly from participant narratives rather than being imposed by a pre-existing theoretical framework. Transcripts were imported into Dedoose (Version 9.0.107), a cloud-based platform for qualitative and mixed-methods analysis, to facilitate coding and codebook development. After transcribing 20 interviews, an initial codebook was developed by co-authors RD and JM, who bring complementary multidisciplinary perspectives to the analysis [29]. RD, with expertise in clinical practice, and JM, with a background in behavioral science and public health research, contributed distinct viewpoints that enriched the interpretation of participant responses and enhanced the depth and rigor of the coding framework. Each transcript was independently reviewed and coded by two members of the research team (BB, CM, JM), who were blinded to each other's coding to enhance analytical rigor. Following independent coding, the coders met to reconcile discrepancies, and code definitions were revised to improve clarity and consistency, as needed, throughout the entire process. Dedoose automatically time-stamped each coded excerpt, enabling documentation of coding activity and internal audit procedures. To enhance the rigor, intercoder reliability was assessed using Dedoose's Testing Center feature. The pooled kappa summarizes rater agreement across multiple codes to evaluate agreement beyond chance.

The participants' narratives often included personal histories of weight gain, shaped by factors such as lifelong struggles with obesity, sedentary work environments, having children, aging, and menopause. These contextual experiences informed how these individuals perceived their susceptibility to obesity-related conditions, the severity of their current health status, the potential benefits and barriers of GLP-1RA therapy and their interactions with care professionals. For example, one 39-year-old White female described the confusion around her inability to lose weight despite professional support: "When I'm with a dietitian, she's like, I don't know why you're not losing weight other than you might be going into menopause." Another participant, a 47-year-old White male, reflected on how life transitions contributed to gradual weight gain over nearly two decades: "Then once I got married, then the weight really started going on. I was in graduate school, and wasn't active, and then we had kids, and I was even less active, life stress, and so…the weight gain has been probably pretty gradual for 20 years now. It's been pretty steady." These personal accounts highlight how weight gain is often experienced as a cumulative and multifactorial process deeply intertwined with life events and physiological changes.

Belief in the potential to prevent obesity-related health problems emerged as an important motivator among participants considering GLP-1RA medication. A 34-year-old White female shared, "My entire family has diabetes, and I haven't been diagnosed with it yet. I'm trying to stop from being diagnosed diabetic," while another 59-year-old White female noted, "I'm not big on medicine and surgeries… but I also don't want to be on cholesterol medicine and high blood pressure medicine… I see it [GLP medication] as it could be a preventative."

The perceived seriousness of obesity and its long-term consequences also emerged as a key theme among those considering GLP-1RA medication. Concerns about future health risks spanned age groups. A 21-year-old White female, for example, expressed fear about losing mobility due to her sedentary lifestyle: "I do have a sedentary lifestyle. I don't really have a whole lot of control over it. And it's very scary to be afraid of losing the mobility I do have." Similarly, a 46-year-old Hispanic female emphasized the potential for chronic illness and premature death as a decisive factor in considering weight loss interventions: "My risk of earlier death or more chronic illness or something, if that is to the point of concern, then I think that is the number one thing that would really tip me in that decision to start to be able to lose weight." These reflections illustrate how some participants' recognition of the severity of obesity, both in terms of physical limitations and life-threatening outcomes, strongly influenced their openness to considering treatment options such as GLP-1RA therapy.

The participants identified numerous perceived benefits of GLP-1RA therapy, particularly in association with the presumed weight loss. They connected this outcome to reduced health risks, improved overall well-being, and enhanced quality of life. A 22-year-old White female described her motivation as being rooted in her family history: "I would say it's always been on my mind because of my hereditary [risk] and being predisposed to cardiovascular disease. But now I feel I should try to lose weight to prevent that." Similarly, a 34-year-old White male emphasized the importance of maintaining health for family responsibilities: "I'm just trying to get myself in better shape for my family. I've got a 3-year-old son. I'd like to be around for him." And a 46-year-old White female highlighted the broader physical and emotional benefits of weight loss: "Obesity causes a lot of things in your body. It's hard on your joints and on your heart. If you're getting relief in other areas as well, that's huge—because if it helps with your inflammation and your body hurts all the time, that's why you don't exercise. Hopefully, getting that weight off and helping with the inflammation means I'll feel up to being more active. Being more active burns more calories, and that, along with getting your endorphins going, heightens your mood."

Among respondents who reported specific health conditions, (i.e., hypertension or heart disease (35%) and anxiety and/or depression (45%)), only one participant explicitly expressed an expectation that their condition would improve with GLP-1RA use. In contrast, two of the six participants with joint or back pain conveyed hope that weight loss would alleviate their discomfort. As one 79-year-old White male noted, "I would like to get around a lot better. I'd like to be able to walk through a supermarket without using one of those electric scooters."

This response may reflect a broader public understanding that excess body weight is directly associated with musculoskeletal conditions, including osteoarthritis and back pain, whereas the connections between obesity and cardiovascular or mental health outcomes, though well-established in the scientific literature, are less widely recognized among the general population [33,34,35].

Numerous barriers were cited by Group 1 participants, likely contributing to their hesitancy in initiating GLP-1RA therapy, despite a shared recognition that weight loss was an important health priority. These barriers included eligibility, safety concerns, cost, and social perceptions that commonly deter individuals from initiating pharmacologic weight-management interventions [14,20,36,37,38].

Participants in this group demonstrated limited knowledge and mixed opinions regarding the safety, potential effects, and anticipated duration of GLP-1RA use, which can play a role in the decision-making process. When surveyed about perceived safety, males were more unconcerned than females (18% vs. 86%) although nearly one-quarter (23%) reported never having considered the issue. Most participants (approximately 75%) were unable to identify any potential side effects, and nearly one-third (32%) were unsure as to whether GLP-1RAs would be prescribed as a short-term aid or a lifelong therapy. This uncertainty aligns with recent evidence showing that public understanding of GLP-1RAs remains limited, particularly regarding their mechanism, long-term effects and duration of treatment, despite their increasing visibility in popular media [46,47].

While baseline knowledge was limited, social exposure and peer influence often acted as informal cues prompting reconsideration of GLP-1RA therapy. Participants frequently mentioned hearing about the medication through family, coworkers, or social media. A 56-year-old mixed-race female shared that she had "seen some pretty incredible results for some of [her] family members," which led her to wonder if "maybe this is the thing that will get me over that hump" of constantly thinking about food and dieting. Similarly, a 47-year-old White female admitted, "I am not immune from the social media influence that seems to point to dramatic changes for people who take it," while a 34-year-old White female described coworkers enthusiastically urging her to "get on it as soon as you can."

These narratives illustrate how vicarious experiences and media exposure can shape perceptions of efficacy and safety, often filling an informational void left by limited professional guidance. Such findings parallel recent analyses showing that online communities and social media platforms have become dominant sources of information and misinformation about GLP-1RAs, amplifying enthusiasm while downplaying risks [48,49]. For some, these social comparisons intersect with age-related concerns about metabolism and weight maintenance. As one 54-year-old White male observed, "metabolism and age has really kind of caught up with me within the course of the past five to maybe seven years," suggesting how personal experiences of aging may compound openness to pharmacologic solutions.

Collectively, these findings highlight a disconnect between widespread social awareness of GLP-1RAs and the relatively low level of clinical understanding among potential users. This imbalance underscores the need for proactive, evidence-based education to help individuals differentiate between anecdotal success stories and the medical realities of long-term pharmacologic weight management [14,19,48].

Self-efficacy, the confidence in one's ability to initiate and sustain behaviors required for weight loss, influenced participants' consideration of GLP-1RA medication within the framework of the Health Belief Model. On the standardized perceived competence scale, which closely reflects self-efficacy, this group scored in the lowest tertile (mean = 3.9), indicating limited confidence in their ability to achieve meaningful weight loss through personal effort alone compared to the other groups that had initiated GLP-1RA therapy [50,51]. This finding aligns with prior research showing that individuals with obesity frequently report diminished self-efficacy for weight control, particularly after repeated unsuccessful attempts at dieting or exercise [52,53].

Consistent with this interpretation, 90% of participants who were thinking about GLP-1RA medication reported having tried multiple weight loss strategies such as diet modification and exercise, and approximately one-third had previously used weight-loss medications without achieving sustained results. This pattern of repeated but unsuccessful effort likely reinforces perceptions of limited personal control and reduces motivation to engage in future attempts, a dynamic well-documented in behavioral models of obesity treatment [54,55]. Interestingly, even among those with objectively higher activity levels, as measured by the physical activity questionnaire (IPAQ), self-efficacy remained low. Although 32% of participants scored high on the IPAQ, suggesting they were already engaging in above-average physical activity, many still reported difficulty losing weight. However, self-efficacy varied among participants. One 56-year-old multiracial female demonstrated notable decisional confidence, stating, "If I decide to do this, I would have a pretty open dialogue with a number of people who really matter to me. I have no one in my life who would discourage any path I choose to take." Her statement suggests a high level of confidence in managing her own health decisions, supported by positive social reinforcement, a factor that, according to the HBM, enhances self-efficacy through social persuasion and interpersonal cues to action [51,56].

Cost emerged as a prominent theme across interviews and was consistently identified as a significant barrier to initiating GLP-1RA treatment. Participants expressed concern about affordability, particularly in light of recent decisions by private insurers to discontinue coverage for weight loss for non-diabetic patients starting in 2026. These policy changes, often justified by insurers as necessary to manage unsustainable costs, have shifted financial responsibility to employers or imposed behavioral prerequisites and preauthorization requirements [58,59]. For many individuals, especially those with limited financial resources, such changes represent a substantial obstacle to accessing treatment.

In response to these coverage gaps, some participants reported considering compounded versions of GLP-1RA medications, which are typically less expensive but may lack the rigorous regulatory oversight of FDA-approved products [60]. While compounding has historically offered an alternative for uninsured or underinsured patients, recent FDA actions to restrict compounding due to safety concerns have introduced new challenges. Patients who previously relied on compounded medications now face uncertainty regarding both affordability and availability, potentially exacerbating disparities in access to obesity treatment [40].

Beyond cost and access, participants expressed uncertainty about their candidacy for GLP-1RA therapy, potential side effects, long-term safety, and treatment duration. These concerns highlight the need for proactive, clinician-initiated conversations that clearly outline the benefits, risks, and expectations regarding therapy. Our findings suggest opportunities for clinicians to support shared decision-making by acknowledging patients' current health behaviors, such as exercise and dietary changes, before offering generalized lifestyle recommendations. Documenting prior weight loss efforts (e.g., diet, physical activity, previous medication use) in the medical record may also facilitate insurance approval for GLP-1RA therapy, which often requires evidence of unsuccessful conventional approaches [61].

Importantly, clinicians should not interpret a patient's silence or lack of inquiry about GLP-1RA therapy as disinterest. As described by the participants, such silence may reflect uncertainty about eligibility, limited awareness of therapeutic benefits, or discomfort initiating the conversation. Given this ambiguity, clinicians should take the lead in introducing GLP-1RA as a potential treatment option, particularly when patients present with obesity-related health concerns or express interest in weight management. Prior research suggests that patients are more likely to pursue treatment when it is endorsed by their physician, underscoring the importance of clinician guidance in facilitating informed decisions [9,62]. Although GLP-1RAs offer several non-weight-related health benefits, participants' awareness of these advantages was limited [63]. Clear communication about risks, expected outcomes, and potential adverse effects is essential to support patient confidence and informed decision-making [1].

Participants' reflections on GLP-1RA therapy as a strategy to prevent obesity-related health conditions align with a robust body of literature demonstrating the link between obesity and chronic diseases, such as cardiovascular disease, type 2 diabetes, infertility, and increased mortality [64]. Notably, during the COVID-19 pandemic, obesity was identified as a major risk factor for severe outcomes, including hospitalization, ICU admission, and death [65,66]. A large-scale study involving over two million individuals found that GLP-1RA use, compared to usual care, was associated with a reduced risk of developing diabetes and other chronic conditions, highlighting its potential as a preventive therapy [67]. These findings illustrate how personal and familial health histories can shape motivation to pursue pharmacologic interventions aimed at disease prevention.

Participants' perceptions of the benefits of GLP-1RA therapy are consistent with existing studies indicating that perceived health benefits. For example, preventing chronic disease or improving physical functioning can serve as strong motivators for weight loss and sustained health behavior change. Overall, participants' views on the benefits of weight loss aligned with public health evidence showing that modifiable risk factors, including poor diet, physical inactivity, and obesity, contribute to nearly 50% of premature deaths in the United States [68,69,70]. Moreover, preventive health behaviors like weight management not only improve individual health outcomes but also reduce long-term healthcare costs compared to treating chronic conditions after onset [71,72].

This study also highlights the complex interplay between behavioral effort, perceived competence, and outcome expectations, emphasizing that self-efficacy is shaped not only by actions but also by the perceived success of those actions [52,54]. Low self-efficacy has been shown to predict reduced adherence to lifestyle interventions and hesitation to initiate new treatments, such as pharmacotherapy [54,55]. For some participants, GLP-1RA therapy represented an external solution compensating for perceived limitations in willpower or behavioral control, an expression of the Health Belief Model's construct of low self-efficacy, or limited belief in one's ability to take effective action toward change [51]. In this context, low perceived competence may reduce the likelihood of initiating treatment, even when perceived benefits are high.

Interestingly, self-efficacy and decisional confidence diverged. While many participants reported limited confidence in their ability to lose weight independently, some expressed high confidence in their autonomy to make treatment decisions. This form of decisional self-efficacy may enhance openness to pharmacologic interventions when they align with personal values and trusted social networks. Consistent with prior research, these findings underscore the need for interventions that not only provide accurate information about GLP-1RA therapy but also foster patients' confidence in their ability to make and sustain informed health choices [68,73].

This mixed-methods study provides a foundation for future research aimed at improving patient-centered GLP-1RA care. Future studies should intentionally include diverse populations, such as men, rural populations, and individuals from different socioeconomic and cultural backgrounds, to examine how perspectives vary across social and economic contexts. Additional research is needed to generate robust data on the long-term effects of GLP-1RA therapy and to develop strategies for effectively disseminating emerging information to patients seeking safety guidance. Finally, clinician-focused interventions should aim to identify best practices for initiating conversations about GLP-1RA medications with patients who have obesity, including those with and without co-morbidities; establish evidence-based guidelines for an optimal follow-up schedule; and standardize educational materials on nutrition and physical activity to support informed, patient-centered decision-making.

The results of this study should be considered in light of its limitations. We wanted to capture a point in time when GLP-1RA medications were surging in use. Although this study was not limited to a single site, we relied on prescription refill information and clinician referrals within one health care system as the primary recruitment strategy. This approach may have introduced selection bias and limited the diversity of perspectives. Most participants were White and female, which reflects broader prescribing trends, as women are more likely to use a GLP-1RA medication for obesity alone [74].