Ghusn, Wissam

Abstract Disclosure: S. Fansa: None. W. Ghusn: None. E. Tama: None. B. Nicolalde: None. D. Anazco: None. S. D'Andre: None. S. Faubion: None. C. Shufelt: None. A. Acosta: None. M.D. Hurtado: None. Background: Aromatase inhibitors (AIs) block estrogen synthesis and are used as adjuvant treatment for breast cancer. AIs are associated with weight gain that can lead to increased cardiometabolic risk, thereby affecting health and survivorship quality in these patients. The role of anti-obesity medications (AOMs) in patients using AIs has not been studied. We sought to investigate weight loss outcomes to AOMs in patients taking AIs for breast cancer treatment. Methods: This is a matched case-control retrospective cohort study of breast cancer survivors on AI using FDA-approved AOMs (AI/AOM group). We compared their weight loss outcomes with a group of female patients with obesity, without a history of breast cancer or AI use, on AOMs (AOM group). We matched patients by age and body mass index (BMI). Exclusion criteria: AOM initiation prior to AI therapy, ≤3 months of AOM use, history of bariatric surgery, active malignancy, or pregnancy. Primary endpoint: total body weight loss % (TBWL%) at 12 months. Secondary endpoints: TBWL% at 3 and 6 months and % of patients achieving categorical TBWL ≥5%, ≥10% and ≥15% at 12 months. We used Pearson χ2 and unpaired t-test to compare baseline characteristics and outcomes between groups, and univariate analyses to estimate the contribution of variables to TBWL% in the AI/AOM group. We present results as mean ± standard deviation. Results: We included 99 patients: 63 in the AI/AOM group (63.5±10 years, BMI 34.4±7.0 kg/m2) and 36 in the AOM group (60.4±8.7 years, BMI 36.3±6.9 kg/m2). Liraglutide, semaglutide and phentermine were the only AOMs used. There was no difference in the frequency of use of these three AOMs among both groups (p= 0.1). AI/AOM group had a lower TBWL% compared to the AOM group during follow-up: 3.7± 4.3% vs. 5.6 ± 4.1% (p= 0.03) at 3 months, 3.9± 4.3% vs. 9.5± 4.7% (p< 0.0001) at 6 months, and 5.2± 5.3% vs. 10.5± 6.8% (p< 0.0001) at 12 months. Although the AI/AOM group was more likely to use lower doses of AOMs (p= 0.0004), TBWL% differences persisted among groups at 12 months after adjusting for AOM dosing (p< 0.0001). There was no difference in nutritional and behavioral modification sessions among groups (p=0.06 and p=0.9, respectively). At 12 months, the percentage of patients achieving ≥5%, ≥10%, and ≥15% TBWL was greater in the AOM group compared to the AI/AOM group: ≥5% TBWL, 85.7% vs. 50.0% (p< 0.0001); ≥10%, 57.1 vs. 20.0% (p< 0.0001); and ≥15%, 28.6 vs. 5.0% (p< 0.0001); respectively. We found no predictors of TBWL% at 12 months in the AI/AOM group. Conclusion: Weight loss outcomes in breast cancer survivors on AIs taking AOMs are poorer compared to patients without breast cancer history and not taking AIs. Studies are needed to assess the mechanisms behind the different weight loss response to AOMs in women taking AIs, which we hypothesize may relate to AIs’ anti-estrogenic effect on lean and fat mass. Presentation: Friday, June 16, 2023

Abstract Disclosure: S. Fansa: None. W. Ghusn: None. B. Nicolalde: None. D. Anazco: None. E. Tama: None. A. Acosta: None. M.D. Hurtado: None. Introduction: The increasing prevalences of obesity and type 2 diabetes (T2D), the “twin epidemics”, have led to the development of drugs targeting both diseases simultaneously. Liraglutide and semaglutide, GLP-1 receptor agonists used for T2DM, are also FDA-approved for weight loss. Tirzepatide, a novel dual GIP/GLP-1 receptor agonist approved for T2D, has shown promising weight loss outcomes in clinical trials. To date, no study has assessed weight loss outcomes of tirzepatide in a real-world setting. Our aim is to assess its efficacy and safety in patients with overweight or obesity. Methods: This is a retrospective cohort study of adults with overweight or obesity taking weekly subcutaneous tirzepatide for T2D or off-label for weight loss. We excluded patients taking tirzepatide for less than one month, prior bariatric procedure, use of any anti-obesity medications, and active malignancy or pregnancy. The primary outcome was total body weight loss percentage (TBWL%) at 3 months. Secondary outcomes included TBWL% at 1 and 2 months; TBWL% difference by T2D status (with and without) and by sex at 3 months; proportion of patients achieving ≥5%, ≥10%, and ≥15% of TBWL% at 3 months; predictors of TBWL% at 3 months; and reported side effects during follow up. We used paired t-test to assess TBWL% compared to baseline, non-paired t-test to compare TBWL% by T2D status and sex, and univariate analyses to estimate the contribution of other variables to TBWL%. Results are presented as mean ± standard deviation. Results: We included 175 participants (81% female, age 49.8±12.2, 91% white, BMI 38.8±7.3 kg/m2). One third of patients had T2D (n=59, 34%). Most patients were on 5mg (39%) or 7.5mg (22%) of tirzepatide weekly. TBWL% at 1, 2, and 3 months was 3.6±2.5% (n=87), 5.8±3.5% (n=100), and 8.4± 4.3% (n=60), respectively (p <0.0001 compared to baseline at all timepoints). Patients with T2D lost less weight at 3 months compared to patients without T2D: 6.9±4.0% vs. 9.1±4.4% (p= 0.03). At 3 months, TBWL% was greater in females, 9.2±4.3% vs. 5.0±2.5% for males, p<0.0001. Greater baseline weight was associated with greater TBWL% (R=0.32, p<0.0001). At 3 months, 60 patients had documented weights with 81.6% achieving ≥ 5%, 30% achieving ≥10%, and 10% achieving ≥15% TBWL. Forty participants (23%) reported side effects. The most frequent were nausea/vomiting (n=27, 15%), constipation (n=6, 3%), and abdominal pain (n=5, 3%). Eight patients (5%) had to either decrease dosage or discontinue the drug due to side effects. Conclusion: In this retrospective cohort study, tirzepatide led to substantial weight loss at 3 months. Patients with T2DM lost less weight than patients without. Further real-world studies with longer follow-up duration and higher tirzepatide doses are needed to establish the long-term efficacy, safety, and tolerability of this drug in this setting. Presentation: Friday, June 16, 2023

ABSTRACT Enterocolic fistulae lead to abnormal diversion of gastrointestinal contents from the small intestine to the colon, causing diarrhea and protein energy malnutrition. We describe a rare case of a 40-year-old patient presenting with chronic diarrhea, unintentional weight loss, sitophobia, and severe abdominal pain in the setting of extensive thrombosis due to JAK2 V617F mutant disorder and associated tobacco use. Computed tomography enterography demonstrated an enterocolic fistula (jejunum to cecum), and a colonoscopy confirmed a 4 mm fistula in the cecum. The patient was nutritionally optimized with plans for a surgical fistula takedown in the future.

ImportanceNo retrospective cohort study has assessed the effectiveness of semaglutide at doses used in randomized clinical trials to treat obesity (ie, 1.7 and 2.4 mg).ObjectiveTo study weight loss outcomes associated with semaglutide treatment at doses used in randomized clinical trials for patients with overweight or obesity.Design, Setting, and ParticipantsThis cohort study, conducted at a referral center for weight management, retrospectively collected data on the use of semaglutide for adults with overweight or obesity between January 1, 2021, and March 15, 2022, with a follow-up of up to 6 months. A total of 408 patients with a body mass index (BMI) of 27 or more were prescribed weekly semaglutide subcutaneous injections for 3 months or more. Patients with a history of bariatric procedures, taking other antiobesity medications, and with an active malignant neoplasm were excluded.ExposuresWeekly 1.7-mg or 2.4-mg semaglutide subcutaneous injections for 3 to 6 months.Main Outcomes and MeasuresThe primary end point was the percentage of weight loss. Secondary end points were the proportion of patients achieving weight loss of 5% or more, 10% or more, 15% or more, and 20% or more after 3 and 6 months and the percentage of weight loss for patients with or without type 2 diabetes after 3 and 6 months.ResultsThe study included 175 patients (132 women [75.4%]; mean [SD] age, 49.3 [12.5] years; mean [SD] BMI, 41.3 [9.1]) in the analysis at 3 months and 102 patients at 6 months. The mean (SD) weight loss after 3 months was 6.7 (4.4) kg, equivalent to a mean (SD) weight loss of 5.9% (3.7%) (P < .001), and the mean (SD) weight loss after 6 months was 12.3 (6.6) kg, equivalent to a mean (SD) weight loss of 10.9% (5.8%) (P < .001 from baseline). Of the 102 patients who were followed up at 6 months, 89 (87.3%) achieved weight loss of 5% or more, 56 (54.9%) achieved weight loss of 10% or more, 24 (23.5%) achieved weight loss of 15% or more, and 8 (7.8%) achieved weight loss of 20% or more. Patients with type 2 diabetes had a lower mean (SD) percentage weight loss at 3 and 6 months compared with those without type 2 diabetes: 3.9% (3.1%) vs 6.3% (3.7%) at 3 months (P = .001) and 7.2% (6.3%) vs 11.8% (5.3%) at 6 months (P = .005).Conclusions and RelevanceThe results of this cohort study suggest that weekly 1.7-mg and 2.4-mg doses of semaglutide were associated with weight loss similar to that seen in randomized clinical trials. Studies with longer periods of follow-up are needed to evaluate prolonged weight loss outcomes.