Abstract
Background:
Weight loss is the mainstay of management for patients with metabolic dysfunction-associated steatotic liver disease. We studied the impact of referral to MOVE!, a nationally-implemented behavioral weight loss program, on weight in MASLD patients.
Methods:
This retrospective cohort study included 102,294 MASLD patients from 125 Veterans Health Administration centers from 2008–2022.
Results:
Most patients lost no significant weight or gained weight. Increased engagement with MOVE! was associated with greater hazard of significant weight loss compared to no engagement.
Conclusion:
A minority of patients experienced significant weight loss through 5 years using lifestyle interventions alone.
Graphical Abstract
Introduction
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a leading cause of liver disease, with an estimated worldwide prevalence >30% (1). In the US, where predisposing metabolic risk factors are common, rates of MASLD are expected to increase (2, 3). Currently, weight loss is the mainstay of management (4–6); first-line measures include lifestyle changes incorporating diet and exercise (3). While weight loss of >7–10% body weight is associated with histologic resolution of steatohepatitis, few patients achieve this with lifestyle interventions alone (7), and even fewer are able to sustain weight loss (8). Delays in achieving significant weight loss increase the risks of progressive fibrosis, metabolic and cardiovascular morbidity, and cancer (3). As formalized behavioral interventions for MASLD become increasingly common (9, 10), evaluation of such programs is imperative. MOVE! is a nationally implemented weight loss program in the US Veterans Health Administration (VHA) incorporating dietary changes, lifestyle interventions, and behavioral strategies through in-person and telemedicine visits; referral is initiated by providers, but all veterans are eligible to participate. We studied the impact of MOVE! referral on weight trajectories in patients with MASLD, and secondarily evaluated utilization of weight loss pharmacotherapy and bariatric surgery.
Methods
This was a retrospective cohort study of VHA patients with body mass index (BMI) ≥35kg/m2 and MASLD, identified using a validated algorithm (11, 12), who were referred to MOVE! between 1/2008–12/2022 (additional details in Supplement). Baseline demographic, BMI, and comorbidity data were collected. Patients were stratified into 4 groups: “minimal”, “low”, “moderate”, and “high” engagement were defined as attending 0–1, 2–5, 6–12, or >12 MOVE! appointments, respectively, in the year following referral. “High” engagement corresponded to the >90th percentile of the distribution. Time-updated BMI was ascertained every 90 days through 5 years of follow-up. Median spline curves for percent BMI change over time were plotted for each group, with observations censored at time of bariatric surgery (Roux-en-Y gastric bypass, sleeve gastrectomy, gastric banding), initiation of weight loss pharmacotherapy (semaglutide, liraglutide, tirzepatide, phentermine/topiramate, bupropion/naltrexone, orlistat), or maximum follow-up. Stacked bar charts depicting percentage weight change (cut points 5%, 7%, 10%) over time were evaluated. Finally, multivariable Cox regression was used to estimate the hazard of clinically significant weight loss (≥10%) as a time-to-event outcome for engagement groups, adjusted a priori for age, sex, race/ethnicity, baseline diabetes, and baseline coronary artery disease. All analyses were performed using STATA 18.0/BE (College Station, TX).
Results
102,294 patients from 125 VHA centers were included in the analytic cohort (Table 1). The cohort was 87.4% male, 60.7% white, with baseline median age 55 years (IQR 45, 63), BMI 39.0 (IQR 36.8, 42.4); 39.4% had diabetes. The “minimal”, “low”, “moderate”, and “high” engagement groups comprised 55.1%, 21.2%, 13.1%, and 10.6% of the total cohort, respectively. The high engagement group had the highest baseline median BMI and age, proportion of females, prevalence of diabetes and coronary artery disease, and were more often White. In the overall cohort, most patients either lost no weight or gained weight (Figure 1B). When stratified by engagement with MOVE!, a higher proportion of patients with high engagement experienced significant weight loss (Figure 1A/C/D) vs. minimal engagement, and weight loss occurred earlier during follow-up. In adjusted analysis, high engagement was associated with a 46% increased hazard of achieving ≥10% weight loss (HR 1.46, 95% CI 1.40–1.52, p<0.001), and moderate engagement with 19% increased hazard (HR 1.19, 95% CI 1.14–1.23, p<0.001), relative to minimally engaged patients. Over median 36 months follow-up (IQR 12, 54), 976 patients (1.0%) received bariatric surgery at median 19.7 months from MOVE! referral (IQR 9.9, 35.6); 8,734 patients (8.5%) initiated weight loss pharmacotherapy at median 22.8 months from referral (IQR 8.3, 41.9). Patients with high engagement were more likely to undergo bariatric surgery and/or initiate weight loss pharmacotherapy (each p<0.001; Table 2).
Table 1 –
Baseline Cohort Characteristics, Overall and Stratified by MOVE! Engagement
| All Patients (N=102,294) | Minimal Engagement (N=56,336) | Low Engagement (N=21,638) | Moderate Engagement (N=13,444) | High Engagement (N=10,876) | p-value | |
|---|---|---|---|---|---|---|
| Age, median (IQR) | 55 (45, 63) | 54 (43, 63) | 55 (45, 63) | 57 (47, 64) | 59 (50, 65) | <0.001 |
| Sex | <0.001 | |||||
| Female | 12,920 (12.6%) | 6,568 (11.7%) | 2,756 (12.7%) | 1,963 (14.6%) | 1,633 (15.0%) | |
| Male | 89,374 (87.4%) | 49,768 (88.3%) | 18,882 (87.3%) | 11,481 (85.4%) | 9,243 (85.0%) | |
| Race/Ethnicity | <0.001 | |||||
| White | 62,048 (60.7%) | 32,890 (58.4%) | 13,296 (61.4%) | 8,571 (63.8%) | 7,291 (67.0%) | |
| Black | 13,731 (13.4%) | 8,197 (14.6%) | 2,793 (12.9%) | 1,642 (12.2%) | 1,099 (10.1%) | |
| Hispanic | 15,360 (15.0%) | 8,688 (15.4%) | 3,245 (15.0%) | 1,954 (14.5%) | 1,473 (13.5%) | |
| Asian | 1,902 (1.9%) | 1,132 (2.0%) | 422 (2.0%) | 192 (1.4%) | 156 (1.4%) | |
| Other | 9,253 (9.0%) | 5,429 (9.6%) | 1,882 (8.7%) | 1,085 (8.1%) | 857 (7.9%) | |
| BMI, median (IQR) | 39.0 (36.8, 42.4) | 38.9 (36.7, 42.1) | 39.1 (36.8, 42.6) | 39.3 (36.9, 42.9) | 39.5 (37.0, 43.1) | <0.001 |
| Diabetes | 40,352 (39.4%) | 21,337 (37.9%) | 8,564 (39.6%) | 5,706 (42.4%) | 4,745 (43.6%) | <0.001 |
| Hypertension | 68,482 (66.9%) | 36,857 (65.4%) | 14,412 (66.6%) | 9,373 (69.7%) | 7,840 (72.1%) | <0.001 |
| Hyperlipidemia | 67,995 (66.5%) | 36,350 (64.5%) | 14,465 (66.8%) | 9,369 (69.7%) | 7,811 (71.8%) | <0.001 |
| Obstructive Sleep Apnea | 38,419 (37.6%) | 19,657 (34.9%) | 8,326 (38.5%) | 5,684 (42.3%) | 4,752 (43.7%) | <0.001 |
| Coronary Artery Disease | 17,972 (17.6%) | 9,361 (16.6%) | 3,882 (17.9%) | 2,574 (19.1%) | 2,155 (19.8%) | <0.001 |
IQR= interquartile range; BMI = body mass index
Figure 1 –
Median BMI Trajectory by Engagement Group (A) and Weight Change Categories in All Patients (B), Minimal Engagement Group (C), and High Engagement Group (D).
Table 2 –
Use of Surgical and Pharmacologic Weight Loss Interventions, Overall and Stratified by MOVE! Engagement
| All Patients (N=102,294) | Minimal Engagement (N=56,336) | Low Engagement (N=21,638) | Moderate Engagement (N=13,444) | High Engagement (N=10,876) | p-value | |
|---|---|---|---|---|---|---|
| Any Bariatric Surgery | 976 (1.0%) | 181 (0.3%) | 168 (0.8%) | 253 (1.9%) | 374 (3.4%) | <0.001 |
| Time to Bariatric Surgery (months), median (IQR) | 19.7 (9.9, 35.6) | 34.8 (23.9, 44.1) | 24.5 (12.4, 43.0) | 16.8 (8.7, 33.7) | 14.0 (9.1, 24.5) | <0.001 |
| Sleeve Gastrectomy | 681 (0.7%) | 125 (0.2%) | 113 (0.5%) | 179 (1.3%) | 264 (2.4%) | <0.001 |
| RYGB | 283 (0.3%) | 50 (0.1%) | 53 (0.2%) | 70 (0.5%) | 110 (1.0%) | <0.001 |
| Gastric Banding | 29 (0.0%) | 9 (0.0%) | 5 (0.0%) | 8 (0.1%) | 7 (0.1%) | 0.005 |
| Any Weight Loss Medication | 8,734 (8.5%) | 3,438 (6.1%) | 1,858 (8.6%) | 1,682 (12.5%) | 1,756 (16.1%) | <0.001 |
| Time to Weight Loss Medication (months), median (IQR) | 22.8 (8.3, 41.9) | 30.1 (15.8, 45.8) | 23.0 (9.1, 42.5) | 14.8 (5.9, 36.1) | 12.4 (5.4, 33.6) | <0.001 |
| GLP-1 receptor agonist* | 6,665 (6.5%) | 2,883 (5.1%) | 1,411 (6.5%) | 1,183 (8.8%) | 1,188 (10.9%) | <0.001 |
| Phentermine/topiramate | 920 (0.9%) | 244 (0.4%) | 159 (0.7%) | 228 (1.7%) | 289 (2.7%) | <0.001 |
| Bupropion/naltrexone | 302 (0.3%) | 75 (0.1%) | 69 (0.3%) | 80 (0.6%) | 78 (0.7%) | <0.001 |
| Orlistat | 2,231 (2.2%) | 539 (1.0%) | 498 (2.3%) | 558 (4.2%) | 636 (5.8%) | <0.001 |
IQR= interquartile range; RYGB=Roux-en-Y gastric bypass; GLP-1= Glucagon-like peptide-1
GLP-1 receptor agonists included liraglutide, semaglutide, and tirzepatide (a GLP-1/GIP agonist)
Discussion
In this large VHA cohort of MASLD patients referred to MOVE!, few patients achieved clinically significant weight loss. We isolated the impact of MOVE! by censoring observations at bariatric surgery or weight loss pharmacotherapy initiation. Patients with high engagement with MOVE! had higher likelihood of weight loss; these patients were older with higher burden of metabolic comorbidities, perhaps suggesting increased urgency to achieve significant weight loss. However, even in this group nearly 70% of patients experienced no weight loss or gained weight. Few patients underwent bariatric surgery despite strong evidence supporting surgical intervention compared to medical management in MASLD (13, 14), consistent with other studies reporting that only 1–3% of eligible patients undergo bariatric surgery (15, 16). Similarly, weight loss pharmacotherapy was not pursued in most patients.
Our results highlight the low efficacy of lifestyle interventions alone for MASLD patients at the population level, and that more aggressive measures of weight loss pharmacotherapy and bariatric surgery are underutilized and unnecessarily delayed. The paradigm for aggressive management of obesity and MASLD should shift to emphasize more effective adjuncts and alternatives to lifestyle modification alone. Future studies may also seek to predict which patients are likely to respond to different management options to individualize care plans. There were also disparities in MOVE! engagement by race/ethnicity that warrant further exploration.
We acknowledge several important study limitations. There is possible misclassification of exposures, however direct outpatient consultation and visits tables were used to ascertain MOVE! visits. Next, there are external validity limitations to VHA data, which are male predominant, however, this integrated health system offers a unique opportunity to evaluate a nationally-implemented weight management program. Third, we did not assess the translation of weight change to additional clinical endpoints such as incident cirrhosis or mortality; this may be the subject of future work. Finally, many VHA centers require MOVE! referral prior to initiation of weight loss pharmacotherapy or surgery; this structural requirement partially explains the positive association between MOVE! engagement and these endpoints.
In conclusion, most patients referred to a national lifestyle-based weight management program did not achieve significant weight loss. Guidelines for weight management in MASLD should be revisited to emphasize more aggressive measures up front in many patients given lack of efficacy of the first-line recommendation.
Supplementary Material
Financial support:
Nadim Mahmud is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (K08-DK124577). He has also received investigator-initiated funding from Grifols unrelated to this manuscript.
ABBREVIATIONS
- BMI
Body mass index
- MASLD
Metabolic dysfunction-associated steatotic liver disease
- VHA
Veterans Health Administration
Footnotes
Potential competing interests: The authors declare no conflicts of interest related to the content of this manuscript.
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