Abstract
Anti-obesity medications (AOMs) have not been studied in survivors of adolescent and young adult (AYA) cancer. In this retrospective analysis, generalized additive mixed model with penalized spline described body mass index (BMI) over time among survivors of AYA cancer prescribed an AOM. Body weight and BMI at pre-AOM maximum and last follow-up were summarized, with 95% confidence intervals. Over a median follow-up time of 249 days, 63.4% of survivors had ≥5% weight reduction. The proportion of survivors with severe obesity decreased from 60% to 35%. These findings suggest that AOMs are effective for weight reduction in survivors of AYA cancer.
Introduction
The prevalence and severity of obesity have increased in the population over the past several decades. 1 Recent data among adolescents and young adults (AYAs) with leukemia found that nearly half were overweight or obese at the time of diagnosis, 2 and prior studies have found an increased prevalence of obesity among survivors of AYA cancer compared with the general population. 3 Obesity is associated with a wide variety of adverse health risk factors and outcomes, including insulin resistance and diabetes, dyslipidemia, hypertension, hepatic steatosis, stroke, and cardiovascular disease (CVD).4,5 Compared with the general population, survivors of AYA cancer are at increased risk for many of these conditions, including dyslipidemia, CVD, stroke, hypertension, and diabetes, 6 and obesity in survivors may potentiate their risk.7,8 As such, effective weight loss interventions targeting cancer survivors with obesity are needed.
Pharmaceutical advances have led to a growing number of anti-obesity medications (AOMs), and recent guidelines for the treatment of obesity include strong recommendations for the use of AOMs in adults with body mass index (BMI) ≥30 or ≥27 kg/m2 with weight-related complications, such as CVD, type 2 diabetes, obstructive sleep apnea, and stroke. 9 Among adults in the general population taking AOMs, retrospective studies in nonclinical trial populations have demonstrated average BMI reduction of nearly 5 kg/m2 with about 40% of patients losing ≥5% of baseline weight at up to 2 years of follow-up.10,11 Given that survivors of AYA cancer are more likely to be obese and are at elevated risk for cardiometabolic chronic health conditions compared with the general population,3,6 AOMs may be an important component of weight reduction strategies in this population. However, data on the efficacy of these agents in survivors of AYA cancer are lacking. In this retrospective analysis, we aimed to explore weight-related outcomes after initiation of an AOM among survivors of AYA cancer.
Methods
This retrospective cohort study was approved by the MD Anderson Cancer Center Institutional Review Board. Data were abstracted from the MD Anderson Cancer Center electronic health record (EHR) from January 19, 2024, to May 15, 2024. Included were survivors of AYA cancer who had been prescribed an AOM, encompassing different medication classes, including empagliflozin, semaglutide, liraglutide, tirzepatide, dapagliflozin, dulaglutide, canagliflozin, ertugliflozin, orlistat, phentermine–topiramate, and bupropion–naltrexone. As AOMs were predominantly prescribed outside of MD Anderson, participants either self-reported AOM use or prescription records were available through shared electronic medical record systems. Start date was recorded as the date in the EHR that the prescription was first noted. For most participants (90.4%), the start date documented in the EHR corresponded to the clinic visit date or to the date the AOM was entered into the MD Anderson medication record, indicating that the actual start date likely occurred at some point prior to the entered start date, between MD Anderson clinic visits. Eight participants (9.6%) had a start date entered at an outside clinic. If no end date was indicated, continuous prescription use through the study follow-up period was assumed. Sociodemographic variables, including sex, age at AOM initiation, race, and ethnicity, were extracted from the EHR, as were body weight and BMI measurements prior to and after AOM initiation.
Demographics and baseline clinical characteristics were summarized using mean, median, standard deviation, and interquartile range or frequency with percentage. Confidence intervals (CIs) for percentages were estimated using Wilson’s method. 12 BMI change from baseline was described with baseline defined as the maximum recorded pre-AOM BMI, and follow-up time for each participant ending with the most recent BMI measurement available within the study period. For each participant, outcome measures were isolated to within ±1000 days of the documented medication start date. The association between BMI and time from documented medication start date was modeled by a mixed-effect generalized additive model with penalized spline over time, clustering on participants. 13 Corresponding bootstrap-estimated standard errors utilized 1000 resampling iterations.
Results
We identified 83 survivors of AYA cancer that had a documented AOM prescription (Table 1). The most common cancer types were breast cancer (27.7%) and hematological cancers (15.7%). The median age at AOM initiation was 44.3 years (interquartile range [IQR]: 40.8–47.2), and the median age at diagnosis was 35.0 years (IQR: 32.0–37.0). Twenty-five percent of survivors were Hispanic, and 12% were Black. The most common prescriptions were GLP-1 receptor agonists (51.8%) or a combination of GIP and GLP-1 receptor agonists (22.9%). Median follow-up time after the reported AOM start date was 249 days, considering that the maximum follow-up time was truncated at 1000 days for this analysis.
Characteristics of Survivors of Adolescent and Young Adult Cancer (n = 83) with a Documented Anti-Obesity Medication Prescription
AOM, anti-obesity medication; IQR, interquartile range; SD, standard deviation.
Mean BMI from baseline to follow-up went from 36.5 ± 7.7 to 32.8 ± 7.6 kg/m2. About one-quarter (22.0%, 95% CI: 14.4–32.1) of survivors had a weight reduction from maximum weight to last follow-up of 5%–10%, 13.4% (95% CI: 7.7–22.4) had a weight reduction of 10% to ≤15%, and 28.0% (95% CI: 19.5–38.6) had a weight reduction of ≥15% (Fig. 1a). This corresponded to a decrease in proportion of survivors with severe obesity (class II and class III) from 60% prior to AOM initiation to 35% at follow-up and increase in proportion with healthy BMI (5%–17%; Fig. 1b). Modeled BMI prior to and after reported AOM start date is shown in Figure 1c and illustrates a maximum BMI occurring on average about a year prior to the recorded AOM date followed by a general decline thereafter.
Discussion
Survivors of AYA cancer are a growing population at increased risk for chronic health conditions. 6 While many risk factors for adverse health outcomes in this population are not modifiable, such as treatment exposures, obesity is a modifiable risk factor for many chronic conditions associated with cancer treatment, including insulin resistance, diabetes, dyslipidemia, hypertension, stroke, and CVD.14–17 Optimization of modifiable risk factors is needed, including effective and sustainable weight reduction strategies. In the current study, we demonstrated that AOMs are effective weight loss agents in survivors of AYA cancer. Importantly, weight loss was sustained throughout the follow-up.
In the general adult population, weight loss achieved with U.S. Food and Drug Adminstration approved AOMs ranges from about 4% to 11% of initial body weight, though this is higher for more recently approved AOMs. 18 Semaglutide, which was prescribed to a little over half of the survivors in the current study, resulted in a 15% mean weight loss over a 68-week follow-up period in a clinical trial in the general population of adults aged 18 years and older with obesity. 19 Our results showing a mean percent body weight loss of 10% suggest that AOMs are associated with comparable weight loss in survivors of AYA cancer. While not studied in cancer survivors, in the general population, weight loss of 5%–10% is associated with reductions in systolic and diastolic blood pressure, serum total cholesterol, low-density lipoprotein cholesterol, triglycerides, and hemoglobin A1c.20–22 Importantly, among cancer survivors, both hypertension and dyslipidemia potentiate treatment-related cardiovascular risk, and prediabetes or diabetes is associated with increased risk of future cardiomyopathy, myocardial infarction, and chronic kidney disease.7,23 Thus, the weight loss observed among survivors of AYA cancer in the current study may lead to reduced burden of chronic conditions.
A strength of this study is that it is one of the first to report sustained weight loss with AOMs among survivors of AYA cancer. However, there are limitations that should be considered. AOM start date was not systematically recorded in the EHR and thus likely occurred prior to the MD Anderson clinic visit on which AOM use was first noted. This limited our ability to describe the time course of weight loss after AOM initiation in survivors. Similarly, if no end date was recorded, we assumed continuous AOM prescription, though participants may have self-discontinued AOM use or not reported prescription discontinuation. Additionally, we were unable to assess other outcomes associated with AOM use such as lipids, hemoglobin A1c, cardiac function, cardiometabolic chronic condition burden, and quality of life as these measures were not routinely available. We were also unable to assess adherence to AOM prescription and, given limitations in sample size, were unable to evaluate differences in outcomes by AOM class as well as factors such as cancer treatment history associated with response to AOMs.
In conclusion, we demonstrated that AOM prescription is associated with clinically significant and sustained weight reduction in survivors of AYA cancer. These findings suggest that AOMs should be considered in eligible survivors. Larger, prospective studies with longer follow-up time are needed to assess the impact of AOMs on obesity-related comorbidity burden in survivors of AYA cancer as well as to evaluate the association between cancer-related and sociodemographic factors and AOM response.
Authors’ Contributions
A.M.B. and M.E.R. conceptualized the study. A.R. performed data curation. C.R.A. performed formal analysis and methodology. A.M.B. wrote the original draft. M.E.R. performed supervision. All authors participated in writing—review and editing.
Footnotes
Author Disclosure Statement
The authors report no conflicts.
Funding Information
This work was funded in part by the NIH Cancer Center Support (Core) Grant P30 CA016672 (M.E.R., C.R.A.).
Data Availability
Data supporting the findings of this study are available upon reasonable request to the corresponding author.