About

Thomas A. Wadden is an Emeritus Professor of Psychiatry at the University of Pennsylvania. He serves as the Director of the Center for Weight and Eating Disorders within the Department of Psychiatry. His educational background includes an A.B. in Psychology from Brown University and a Ph.D. in Psychology from the University of North Carolina. He also holds an honorary M.A. from the University of Pennsylvania. His professional work focuses on obesity treatment, lifestyle modification, and behavioral therapy related to weight management. Dr. Wadden has contributed to research on obesity treatment in primary care practice, weight maintenance, and the behavioral aspects of obesity management, with numerous publications in these areas.

Research topics

• Internal medicine
• Endocrinology
• Medicine
• Pediatrics
• Physical therapy

Selected publications

• Internalized weight stigma, metabolic syndrome, and inflammation in postmenopausal women with obesity

  Brain Behavior & Immunity - Health · 2025-11-01

  articleOpen accessSenior author

  Objective: To determine the relationship of internalized weight stigma with metabolic syndrome (MetS) and markers of inflammation. Methods: = 101) with high or low scores on the Weight Bias Internalization Scale completed a single assessment visit. MetS components (waist circumference, blood pressure, triglycerides, HDL cholesterol, and glucose) were measured, along with body mass index (BMI). Blood samples were drawn to analyze C-reactive protein, interleukin-6, and myeloperoxidase. Participants completed a second measure of internalized weight stigma (Weight Self-Stigma Questionnaire; WSSQ) and reported medications, demographics, depression symptoms, smoking status, and perceived stress (included as covariates). Results: = 0.030). Both measures of internalized weight stigma were associated with greater continuous blood pressure values. Inflammatory markers were not associated with internalized weight stigma in most analyses. Conclusions: Some significant associations were found between internalized weight stigma and MetS components, but more research is needed to clarify these relationships.

  PublisherDOI

• Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity

  New England Journal of Medicine · 2025-06-22 · 132 citations

  article

  BACKGROUND: Semaglutide at a dose of 2.4 mg has established weight-loss and cardiovascular benefits, and cagrilintide at a dose of 2.4 mg has shown promising results in early-phase trials; the efficacy of the combination (known as CagriSema) on weight loss in persons with either overweight and coexisting conditions or obesity is unknown. METHODS: In a phase 3a, 68-week, multicenter, double-blind, placebo-controlled and active-controlled trial, we enrolled adults without diabetes who had a body-mass index (BMI; the weight in kilograms divided by the square of the height in meters) of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication. Participants were randomly assigned in a ratio of 21:3:3:7 to receive the combination of semaglutide at a dose of 2.4 mg and cagrilintide at a dose of 2.4 mg, semaglutide alone at a dose of 2.4 mg, cagrilintide alone at a dose of 2.4 mg, or placebo, plus lifestyle interventions for all groups. The coprimary end points were the relative change in body weight and a reduction of 5% or more in body weight from baseline to week 68 with cagrilintide-semaglutide as compared with placebo. Body-weight reductions of 20% or more, 25% or more, and 30% or more were assessed as confirmatory secondary end points. Effect estimates were assessed with the treatment-policy estimand (consistent with the intention-to-treat principle). Safety was assessed. RESULTS: A total of 3417 participants underwent randomization, with 2108 assigned to receive cagrilintide-semaglutide, 302 to receive semaglutide, 302 to receive cagrilintide, and 705 to receive placebo. The estimated mean percent change in body weight from baseline to week 68 was -20.4% with cagrilintide-semaglutide as compared with -3.0% with placebo (estimated difference, -17.3 percentage points; 95% confidence interval, -18.1 to -16.6; P<0.001). Participants receiving cagrilintide-semaglutide were more likely than those receiving placebo to reach weight-loss targets of 5% or more, 20% or more, 25% or more, and 30% or more (P<0.001 for all comparisons). Gastrointestinal adverse events (affecting 79.6% in the cagrilintide-semaglutide group and 39.9% in the placebo group), including nausea, vomiting, diarrhea, constipation, or abdominal pain, were mainly transient and mild-to-moderate in severity. CONCLUSIONS: Cagrilintide-semaglutide provided significant and clinically relevant body-weight reductions in adults with overweight or obesity, as compared with placebo. (Funded by Novo Nordisk; REDEFINE 1 ClinicalTrials.gov number, NCT05567796.).

  PublisherDOI

• Anti-obesity medication for weight loss in early nonresponders to behavioral treatment: a randomized controlled trial

  Nature Medicine · 2025-03-07 · 6 citations

  articleOpen accessSenior author

  Current guidelines recommend behavioral treatment (BT) as the first intervention for patients with obesity. However, a substantial minority (35–50%) do not achieve a clinically meaningful loss of ≥5%. Anti-obesity medications (AOMs) are recommended when target weight loss is not achieved; however, their efficacy among BT nonresponders has not been established. This double-blind, randomized controlled proof-of-principle study evaluated whether augmenting BT with AOM improved 24-week weight loss compared to BT with placebo in early nonresponders to BT. A total of 147 adults with a body mass index ≥31 kg m−2 (≥28 kg m−2 with obesity-related comorbidity) completed an initial 4-week BT run-in. The 76 early nonresponders who lost <2.0% of initial weight were then randomized to 24 weeks of either BT plus placebo (BT + P, n = 38) or BT plus AOM (phentermine = 15.0 mg d−1, n = 38). Early responders received ongoing BT and were not part of the randomized trial. The primary outcome was met; early nonresponders assigned to BT + AOM had a greater mean (±s.e.) reduction in weight of 5.9 ± 0.7% from randomization to week 24, as compared to 2.8 ± 0.7% for those assigned to BT + P (mean difference = 3.1 ± 1.0, 95% confidence interval = 1.1–5.1%, Cohen’s d = 0.73, P = 0.003). Stepping up early BT nonresponders to BT + AOM improves their 24-week weight loss. ClinicalTrials.gov registration: NCT03779048 . A randomized clinical trial showing the superiority of behavioral treatment plus phentermine to behavioral treatment plus placebo for weight loss in those that previously had not responded to behavioral treatment.

  PublisherOA PDFDOI

• Efficacy and safety of a novel oral hydrogel capsule in adults with overweight or obesity: the pivotal randomized <scp>RESET</scp> study

  Obesity · 2025-02-04 · 7 citations

  articleOpen accessSenior author

  OBJECTIVE: The objective of this study was to investigate the efficacy and safety of the Epitomee capsule versus placebo as an adjunct to high-intensity lifestyle intervention in participants with overweight or obesity. METHODS: . The co-primary endpoints at week 24 were percentage change from baseline in body weight for the Epitomee and placebo groups and proportion of Epitomee-treated patients achieving ≥5% weight loss compared with a 35% threshold. The primary safety endpoint was the incidence of device-related serious adverse events. RESULTS: A total of 138 participants received Epitomee and 141 received placebo. Mean (SD) change in body weight from baseline was -6.6% (6.5%) with Epitomee and -4.6% ( 4.7%) with placebo; least-squares means were -6.1% (0.6%) and -4.2% (0.6%), respectively (p = 0.0054). Fifty-six percent of Epitomee-treated participants attained ≥5% weight loss from baseline, which was significantly greater than the 35% predefined threshold (p < 0.0001). Twenty-seven percent of Epitomee-treated and eleven percent of placebo-treated participants achieved ≥10% weight loss. Adverse event rates were similar between the groups. No device-related serious adverse events occurred. CONCLUSIONS: The Epitomee capsule is a safe and efficacious nonpharmacological option for weight management with potential broad application in participants with overweight or obesity.

  PublisherOA PDFDOI

• Intervention adherence, engagement and tool utilization in the breast cancer weight loss (BWEL) trial by race and ethnicity (Alliance A011401).

  Journal of Clinical Oncology · 2025-05-28

  article

  1586 Background: Black and Hispanic breast cancer (BC) survivors have a higher prevalence of obesity and experience less success with weight loss interventions (WLI) than White BC survivors. The BWEL trial (Alliance A011401; NCT02750826) is a phase III randomized trial evaluating the impact of a 2-year telephone-based WLI on invasive disease-free survival in participants (pts) with stage II-III HER2-negative BC and a BMI ≥ 27 kg/m 2 . At 12-months, the WLI induced significant weight loss across demographic factors, including race and ethnicity. However, Black and Hispanic pts lost less weight and completed fewer calls than White pts. Here, we evaluate intervention adherence, engagement and tool utilization in BWEL pts by race and ethnicity. Methods: BWEL randomized pts to a WLI plus health education (HE) or HE alone. WLI pts received semi-structured telephone-based health coaching, delivered in English or Spanish, and received an activity monitor and wireless scale. Pts self-reported race and ethnicity. Mean values for call duration, call density (time to complete the initial 12-week intensive intervention phase), intervention attrition, and frequency of Fitbit use and weight tracking over 12-months were compared by race and ethnicity, comparing least squares means with Tukey-Kramer adjustment for multiple comparisons with adjusted p-values. Results: Of 3181 pts randomized to the study between 08/2016 and 02/2021, 1591 pts were allocated to the WLI arm. 80.5% of pts were White, 12.8% Black, and 7.1% Hispanic. Average BMI was 34.5 (±5.7) kg/m2. Compared to White pts, Black pts had fewer days of Fitbit usage (113.6 vs. 159.8, p&lt;0.0001) and weight tracking (77.9 vs. 135.6 days, p&lt; 0.0001). Hispanic pts had fewer days of Fitbit usage (108.8 vs. 154.9, p= 0.001) and weight tracking (87 vs. 129.5 days, p=0.0002) compared to non-Hispanic pts. There were no differences in attrition rate, average call duration, or call density by race or ethnicity. Conclusions: In a phase III WLI trial, engagement with tools designed to support weight loss was significantly lower in Black and Hispanic pts. Future work is needed to explore ways to enhance engagement and improve weight loss outcomes for racial and ethnic minority pts. Support: U10CA180821, U10CA180882, UG1CA189823; https://acknowledgments.alliancefound.org . Clinical trial information: NCT02750826 . Measure of engagement Race Ethnicity WhiteN=1281 BlackN=204 p-value Non-HispanicN=1459 HispanicN=113 p-value Withdrew from intervention n (%) 58 (4.5%) 13 (6.4%) 0.56 70 (4.8%) 6 (5.3%) 0.51 Call Duration (min)Mean (SD) 34.5 (7.6) 34.6 (9.1) 0.99 34.6 (7.8) 33.3 (7.9) 0.25 Call density(weeks)Mean (SD) 14.2 (7.2) 14.2 (8.8) 0.99 14.2 (7.3) 14.2 (9.7) 0.99 Days of Fitbit UseMean (SD) 159.8 (132.2) 113.6 (124.7) &lt; 0.0001 154.9 (131.8) 108.8 (125.7) 0.001 Days of weight trackingMean (SD) 135.6 (109.5) 77.9 (87.5) &lt; 0.0001 129.5 (108.8) 87 (96.5) 0.0002

  PublisherDOI

• Association of the Early Response to an Oral Shape‐Shifting Superabsorbent Hydrogel Capsule With Weight Loss

  Clinical Obesity · 2025-07-29 · 3 citations

  articleOpen accessSenior author

  Early response (ER) to treatment is predictive of longer-term weight loss. In this post hoc analysis, ER to an oral shape-shifting superabsorbent hydrogel capsule (Epitomee) combined with a lifestyle intervention was compared to placebo combined with a lifestyle intervention. Participants (age = 48.5 ± 12.5 and 48.6 ± 12.4; BMI = 34.1 ± 3.3 and 33.7 ± 3.4, in the Epitomee and placebo groups, respectively) were randomised to Epitomee (N = 138) or placebo (N = 141) with lifestyle intervention. Analyses included body weight measurements taken at baseline, week 8, and week 24. Of the 279 participants enrolled in the study, 250 (90% of the ITT population) provided weight data, including 124 participants in the Epitomee group and 126 in the placebo group. Participants with missing weight data at week 24 were classified as non-responders. Early response (ER) was defined as a weight loss of ≥ 2% at week 8. Weight loss at week 24 was greater in ER to Epitomee compared to placebo (9.3% ± 6.0% vs. 6.9% ± 4.3%; p < 0.0001). The odds ratio for ER to achieve > 5% weight loss at week 24 was 4.10 (95% CI: 1.02, 16.46) for Epitomee and 2.38 (95% CI: 0.62, 9.21) for placebo. A greater proportion of ER to Epitomee, compared to placebo, achieved > 5% (76% vs. 62%; p = 0.0472), ≥ 7% (61% vs. 38%; p < 0.0045) and ≥ 10% (39% vs. 17%; p < 0.0025) weight loss at week 24. ER response to Epitomee was associated with greater weight loss at 24 weeks compared to placebo. Monitoring ER to Epitomee and titrating treatment based on ER may enhance weight loss.

  PublisherOA PDFDOI

• Brain activity associated with breakthrough food preoccupation in an individual on tirzepatide

  Nature Medicine · 2025-11-17 · 5 citations

  articleOpen access

  Obesity and related conditions are associated with distressing food preoccupation that often culminates in dysregulated eating behaviors. Incretin-based therapies can reduce excessive weight in obesity, but their impact on dysregulated eating behaviors remains largely unexamined. Understanding how these pharmacologics engage the brain's mesolimbic circuitry may inform the expansion of their therapeutic potential. We report a rare, first-in-human exploration of the physiological action of these therapies by examining the electrophysiology directly within the human nucleus accumbens. After a short-term course of tirzepatide, the patient-participant exhibited increased severe food preoccupation episodes, which were preceded by an increased delta-theta frequency (≤7 Hz) power in the nucleus accumbens region. We propose that the effects of an incretin-based therapy (tirzepatide) on food preoccupation may be associated with modulation of aberrant activity within this key hub of human mesolimbic circuitry.

  PublisherOA PDFDOI

• Correction: Quality of life improvements associated with weight loss using a novel shape-shifting hydrogel capsule: RESET study results

  International Journal of Obesity · 2025-11-13

  articleOpen access
  PublisherOA PDFDOI

• Weight and cardiometabolic effects of a novel oral shape-shifting superabsorbent hydrogel capsule: Prespecified and exploratory analysis of the Epitomee capsule RESET study

  Obesity Pillars · 2025-01-31 · 3 citations

  articleOpen access

  Background: Management of obesity potentially improves cardiometabolic risk factors in patients with metabolic syndrome (MetS). The Epitomee capsule is a non-pharmacological, biodegradable device treatment for weight reduction in patients with overweight and obesity. Methods: This secondary analysis of the Randomized Evaluation of Safety and Efficacy of the Epitomee capsule Trial (RESET) (a randomized, 24-week, multicenter, placebo-controlled, double-blind trial that enrolled 279 adults aged ≥18 years with a BMI of 27-40 kg/m2) evaluated changes in cardiometabolic parameters in participants treated with Epitomee or placebo combined with lifestyle counseling among (a) the entire RESET study population, and (b) participants meeting diagnostic criteria for prediabetes. Predefined and exploratory endpoints included changes in waist circumference, glycemic parameters, blood pressure, and lipid blood levels; this analysis also assessed percent weight loss in participants with MetS. Results: Waist circumference, systolic and diastolic blood pressure and some measures of glycemia and lipids, improved with both Epitomee and placebo with no significant differences. Participants with prediabetes treated with Epitomee showed significantly greater reductions in HOMA-IR (p < 0.007) and insulin levels (p < 0.003) than the placebo group. Participants with MetS at baseline experienced significantly greater percent change in initial weight when treated with the Epitomee capsule (n = 27) compared to placebo (n = 31), -8.3% vs -5.2 %, respectively (p < 0.0004). Similar percentages of participants with MetS in both groups achieved ≥5 % weight reduction (59.3 % and 54.8 %, in Epitomee and placebo groups respectively). Significantly more participants with MetS treated with Epitomee achieved ≥10 % weight reduction compared with those treated with placebo (40.7 % vs. 6.5 %, respectively, p < 0.002). Conclusion: Treatment with either Epitomee and placebo combined with lifestyle improve cardiometabolic risk factors. Compared to placebo, Epitomee significantly reduced HOMA-IR and insulin levels in participants with prediabetes. Among participants with MetS, Epitomee significantly reduced body weight [ClinicalTrials.gov ID NCT04222322].

  PublisherDOI

• Feasibility and Acceptability of a Psychological Intervention for Internalized Health-Related Stigma Among Adults With Chronic Health Conditions: Preliminary Investigation

  JMIR Formative Research · 2025-07-29 · 1 citations

  articleOpen access

  Background: Health-related stigma is widely acknowledged as a threat to public health and a barrier to managing chronic health conditions. Internalized stigma is a particularly strong predictor of poor health outcomes across health conditions, yet few evidence-based interventions are available. Peer support and counseling have been investigated as interventions for reducing internalized stigma. Typically, these interventions are developed and tested in disease-specific research, focusing on one health condition in isolation from others. This approach may limit knowledge and dissemination of support for health-related stigma across health conditions. Recent work has highlighted the need for research that breaks down traditional silos by using cross-cutting approaches to understand and reduce stigma. Objective: This study aimed to determine the feasibility and acceptability of a new group-based psychological intervention designed to reduce internalized health-related stigma among adults with different stigmatized chronic physical health conditions. Methods: A group intervention that was initially designed to address internalized weight stigma was adapted to be generalizable to other forms of internalized health-related stigma. This was done with input from Advisory Board members living with different stigmatized chronic health conditions and health professionals who specialized in these conditions. Adults with obesity, diabetes, HIV, skin diseases, chronic pain, or cancers were recruited to attend 12 weekly online group meetings. The average session attendance rate was computed with and without makeup sessions. A treatment acceptability questionnaire was completed at week 12. Primarily for feasibility testing, participants completed pre- and post-treatment questionnaires that assessed internalized health-related stigma and other relevant aspects of mental health and health-related quality of life. At baseline, participants were also asked to report reasons for perceived discrimination. Data collection occurred from December 2023 through April 2024. Results: In total, 10 adults were recruited within approximately 6 weeks, of whom 8 attended at least 1 treatment session and completed post-treatment questionnaires, with a 80% retention. The average session attendance rate was 95.8% with makeup sessions and 83.3% for those without makeup. Treatment acceptability ratings were high, with an overall acceptability rating of approximately 6.5 (SD 0.5) out of 7. Medium to large effect sizes were observed for changes in internalized stigma and some aspects of mental health. Almost all (n=7, 87.5%) of participants reported experiencing discrimination due to their health conditions, which accompanied a wide range of other reasons for perceived discrimination. Conclusions: Results showed high feasibility and acceptability of a transdiagnostic, online group psychological intervention for internalized health-related stigma delivered to adults with different types of stigmatized chronic physical health conditions. Given the small sample size and limited generalizability, testing in a large efficacy trial is needed to determine intervention benefits.

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Recent grants

• NIH Grant R01DK056124

  NIH · $1.9M · 2003

• NIH Grant R01HD020152

  NIH · $179k · 1988

• NIH Grant R01HL070301

  NIH · $6.3M · 2014

• NIH Grant R01DK050058

  NIH · $1.2M · 1999

• NIH Grant R01MH049451

  NIH · $1.1M · 1996

Frequent coauthors

• Rena R. Wing

  Miriam Hospital

  186 shared

• David B. Sarwer

  Temple University

  162 shared

• Samuel T. Kuna

  Philadelphia VA Medical Center

  119 shared

• Jesse Chittams

  University of Pennsylvania

  115 shared

• Robert I. Berkowitz

  University of Pennsylvania

  113 shared

• Karen Johnson

  University of Tennessee Health Science Center

  111 shared

• Julio A. Chirinos

  University of Pennsylvania

  109 shared

• Indira Gurubhagavatula

  University of Pennsylvania

  109 shared