Weight Maintenance Success Of Antiobesity Medications After 1 Year
Overview
The high cost of novel glucagon-like peptide-1 receptor agonists (GLP-1 RAs) often limits their accessibility, creating significant barriers to care. This study explored the effectiveness of older, generic anti-obesity medications (AOMs) in sustaining weight loss after a year of GLP-1 RA therapy in individuals who had already achieved notable results.
A prospective analysis was conducted on 105 patients who completed a structured “medical weight loss bundle.” This program included 12 months of GLP-1 RA therapy, followed by 6 months of transition care. The participants had an average baseline body mass index (BMI) of 36.4 kg/m², with weight outcomes monitored at 6, 12, 18, and 24 months.
Of the participants, 40 transitioned to older, generic AOMs after completing GLP-1 RA therapy. After 12 months, this group experienced an average weight loss of 18.3% (95% CI [13.0%, 23.6%]), achieving a mean BMI of 27.9 kg/m². At 18 months, their weight loss was sustained with the same mean BMI. Further follow-up (approximately 1.5 months later) showed additional weight reduction, culminating in an average total weight loss of 25.5% (95% CI [23.1%, 27.9%]) from baseline.
The findings indicate that patients who achieve significant weight loss with GLP-1 RAs can maintain and even enhance these results using cost-effective, older-generation AOMs. This approach has the potential to reduce financial burdens on both patients and insurers, supporting the need for policy revisions to improve access to affordable obesity treatments.
Introduction
Obesity has reached epidemic proportions worldwide in the past two decades, impacting nearly all organ systems, raising the risk of morbidity and mortality, and diminishing quality of life. It is a multifaceted chronic condition influenced by genetic factors, hormonal imbalances, unhealthy diets, lack of physical activity, stress, insufficient sleep, medications, and disruptions to circadian rhythms. Projections suggest that nearly half of Americans will be affected by obesity by 2030, underscoring the need for effective treatments.
While lifestyle modifications are essential, they often fail to provide long-term weight loss in severe obesity due to metabolic adaptations that increase hunger and decrease energy expenditure. Therefore, more intensive treatments like pharmacotherapy and bariatric surgery are necessary. New medications, such as glucagon-like peptide-1 receptor agonists (GLP-1 RAs), have proven effective in helping patients reach a body mass index (BMI) below 30 kg/m² and maintain weight loss for up to four years, outperforming lifestyle changes alone. These drugs also improve weight-related conditions like type 2 diabetes, fatty liver disease, hypertension, cardiovascular issues, and joint pain. However, their high cost limits accessibility, and insurance restrictions—such as requiring a diagnosis of type 2 diabetes or cardiovascular disease—further hinder availability.
Despite the benefits of GLP-1 RAs, discontinuation of treatment often leads to weight regain, as these drugs alter the body’s weight set point by enhancing satiety and reducing appetite. Studies like SURMOUNT-4 and STEP-4 have shown that stopping these medications results in significant weight gain, while continued use maintains or improves weight loss.
To address the obesity crisis, our institution launched a comprehensive weight management program in January 2022, offering a bundled payment model that covers both FDA-approved and off-label antiobesity medications (AOMs), including GLP-1 RAs. This program is designed to minimize out-of-pocket costs for patients and provide multidisciplinary care, offering consultations and services at our obesity center. After the initial 18-month period, patients can continue GLP-1 RA therapy through their insurance or opt for more affordable second-line treatments or lifestyle interventions.
One such alternative is naltrexone/bupropion, a combination medication that aids weight loss by suppressing appetite and promoting satiety. It is recommended for adults with a BMI of at least 30 kg/m² or those with a BMI of at least 27 kg/m² and related comorbidities, such as type 2 diabetes or hypertension. While effective, naltrexone/bupropion has potential side effects, including increased blood pressure, risk of seizures, and depression. It is contraindicated for people with uncontrolled hypertension, seizure disorders, or opioid use.
In a five-year study evaluating common AOMs, medications like metformin, topiramate, and phentermine were frequently used to maintain significant weight loss, with many patients eventually combining multiple treatments to sustain their progress. The study also highlighted the importance of understanding the post-treatment phase, particularly with the recent introduction of GLP-1 RAs, which are not yet fully tested for long-term efficacy.
To explore the effectiveness of weight maintenance beyond one year of GLP-1 RA therapy, our institution initiated a cohort study to assess how well patients can sustain a BMI under 30 kg/m² after transitioning to more affordable, older-generation AOMs. The primary focus is on tracking changes in weight and BMI over 6-month intervals up to two years, providing valuable insights into sustainable, cost-effective weight management strategies.
Method
This study, exempted by the institution’s IRB (initial approval in November 2020; renewed in November 2023), focused on patients enrolled in a structured 18-month “Medical Weight Loss Bundle” (MWLB). The program comprised 12 months of intensive weight management followed by a six-month transition phase. Eligibility required a baseline BMI >35 kg/m², and participants gained access to comprehensive weight loss services, including unrestricted GLP-1 RA therapy for 12 months. Only patients who achieved a BMI ≤30 kg/m² and demonstrated weight stability over 3–6 months were transitioned to the weight maintenance phase, with continued support provided through referrals and generic anti-obesity medication (AOM) prescriptions.
The study exclusively analyzed MWLB participants who completed the initial 12 months of GLP-1 RA treatment between 2022 and 2023, a period coinciding with the activation of extended pharmacotherapy benefits. Retrospective data for 105 eligible patients were extracted from deidentified electronic health records and validated by two reviewers for accuracy. Anthropometric data were collected at baseline and subsequent visits (6-, 12-, 18-, and 24-month marks), alongside patient demographics, comorbidities, weight changes, BMI reductions, and AOM usage.
Anti-obesity medications included FDA-approved therapies like semaglutide, tirzepatide, phentermine, phentermine/topiramate, and naltrexone/bupropion, along with off-label options such as metformin and oral semaglutide. Orlistat was excluded due to poor efficacy and adverse effects. Initial clinical assessments recorded anthropometrics, body composition, and BMI using bioelectrical impedance analysis. Participants were categorized as “completers” (≥2 visits in 12 months) or “noncompleters” (single visit).
Statistical analyses were conducted using SPSS software, with significance determined at p < 0.05. Continuous variables were compared using independent t-tests, while categorical data were analyzed via χ² tests. Repeated-measures design was applied to assess weight changes over time, and results were reported as mean values with 95% confidence intervals.
Result
A total of 105 patients achieved a BMI of <30 kg/m² after 12 months of treatment with Anti-Obesity Medications (AOMs) in the Medical Weight Loss Bundle (MWLB). These patients, with an average age of 45.2 years and a mean baseline BMI of 36.4 kg/m², were predominantly female (92.1%) and White (80.6%). Many had obesity-related conditions, including depression/anxiety (40%), hypertension (26.6%), and type 2 diabetes (8.5%). Some patients had a history of bariatric surgery, with four having undergone Roux-en-Y gastric bypass and three having vertical sleeve gastrectomy.
Of the 105 patients, 7 declined treatment with GLP-1 receptor agonists (RAs) due to side effects, and 4 left the program early. Among those who completed 12 months of GLP-1 RA therapy, 69 patients finished the program, while 36 remained in the pre-weight maintenance phase. Following the MWLB, patients either continued GLP-1 RA treatment, transitioned to generic medications for weight maintenance, or chose lifestyle changes alone. A total of 40 patients were switched to second-generation AOMs such as metformin, phentermine, topiramate, and bupropion after completing the MWLB.
During the MWLB, 69 patients received GLP-1 RA therapy, with 71% using semaglutide 2.0 mg/week and 49% using semaglutide 2.4 mg/week. The total usage of GLP-1 RAs exceeded 100%, as some patients required multiple medications due to shortages, side effects, or diminished efficacy. After transitioning to generic AOMs, 80% of patients were given metformin extended-release, and other medications like phentermine and topiramate were also utilized for weight maintenance.
The average weight loss at 12 months was 22.2%, with 27 patients maintaining a weight reduction at 18 months, resulting in an average BMI of 29.0 kg/m². At 24 months, the weight loss was maintained at 16.1%. However, compliance dropped significantly at the 24-month mark, highlighting the importance of continued medical visits for long-term weight maintenance.
In a subgroup of 40 patients who completed GLP-1 RA therapy and transitioned to second-generation AOMs, the average weight loss at 12 months was 18.3%, resulting in a mean BMI of 27.9 kg/m². These patients also experienced a 12% reduction in body fat percentage. At 18 months, the mean BMI remained stable at 27.9 kg/m², and by the 24-month follow-up, the average BMI was 27.2 kg/m², maintaining a 25.5% weight reduction compared to baseline. This indicates that patients were able to sustain their weight loss with older-generation AOMs after discontinuing GLP-1 RA therapy.
Conclusion
This prospective real-world study highlights the effectiveness of transitioning patients from GLP-1 receptor agonist (RA) therapy to more affordable alternative obesity management medications (AOMs) for sustained weight loss. Patients who had successfully reduced their BMI to below 30 kg/m² after 12 months of GLP-1 RA therapy were able to maintain significant weight loss when switched to generic medications like metformin, topiramate, phentermine, and bupropion. These patients lost an average of 25.1% of their body weight and maintained the reduction for up to 24 months. Additionally, body fat percentage decreased by 10% after the first year.
This strategy is particularly beneficial for patients who lose GLP-1 RA insurance coverage after 12 months, as these older, more cost-effective AOMs can support weight maintenance without the risk of regaining the weight. The combination of GLP-1 RA therapy and these generic AOMs appears to be a promising approach for long-term weight management. In the study cohort, patients demonstrated continued weight loss even after transitioning to AOMs, with an average reduction in BMI from 36.5 to 27.2, and fat mass reduction from 47.1% to 35.5% over 12 months.
However, the study also points to potential challenges, such as the slight but non-significant increase in weight and BMI at the 24-month follow-up, underscoring the importance of ongoing support for weight maintenance. The most frequently prescribed medications—metformin, topiramate, phentermine, and bupropion—target appetite suppression and insulin resistance, enhancing weight loss and fat reduction. These drugs, although less potent than GLP-1 RAs, have proven effective when used in this context.
The study’s findings suggest that older AOMs, after achieving significant weight loss with GLP-1 RA therapy, can help maintain progress by improving insulin sensitivity and reducing hunger. However, it is important to note the study’s limitations, such as its predominantly White, female cohort, which may affect the generalizability of results to more diverse populations. Additionally, factors such as lifestyle modifications, stress, and sleep quality were not fully accounted for, which could have influenced the outcomes.
In conclusion, this research emphasizes the potential of generic AOMs as a viable and cost-effective solution for long-term obesity management. It supports transitioning patients from GLP-1 RA therapy to more affordable oral medications after achieving weight loss, while also calling for further studies to explore these therapies’ effectiveness across a broader demographic. Regular follow-up care is critical to ensure sustained success and address the long-term challenges of weight maintenance.
