Faculty Bibliography

BACKGROUND:Given the cardiovascular, renal, and survival benefits of GLP-1 receptor agonists for diabetes, these agents could be effective among kidney transplant recipients. However, kidney transplant recipients are distinct from GLP-1 receptor agonist trial participants, with longer diabetes duration and severity, greater end-organ damage, increased cardiovascular risk, and multimorbidity. We examined GLP-1 receptor agonist real-world effectiveness and safety in kidney transplant recipients with diabetes. METHODS:This USA-based retrospective cohort study included kidney transplant recipients with type 2 diabetes at transplantation and Medicare as their primary insurance from a national registry linked with Medicare claims. Post-transplantation GLP-1 receptor agonist use was identified through Medicare claims. Death-censored graft loss was estimated using the Fine-Gray sub-distribution hazard model and extended Cox models were used for mortality and safety endpoints. Models incorporated inverse probability of treatment weights. To further test whether bias could affect the main results, a cohort was created in which each GLP-1 receptor agonist user was matched with a kidney transplant recipient who had not started a GLP-1 receptor agonist, was alive with a functioning graft, and had accrued the same amount of post-transplant survival time. FINDINGS/RESULTS:Between Jan 1, 2013 and Dec 31, 2020, we identified 44 536 first time kidney transplant recipients with Medicare as primary payer in the 6 months before and at transplantation. 24 192 patients were excluded as they did not have type 2 diabetes. 2328 patients were ineligible (1916 had missing values and 412 used GLP-1 receptor agonists before transplantation). The primary cohort thus consisted of 18 016 kidney transplant recipients with diabetes. Of these patients, 1969 (10·9%) had at least one GLP-1 receptor agonist prescription filled post-transplant. Compared with patients who had not received a GLP-1 receptor agonist, GLP-1 receptor agonist users were younger (median age at transplant 57 years [IQR 49-64] vs 60 years [51-66], p<0·0001) and more likely to be female (786 [39·9%] vs 5645 [35·2%], p<0·0001). Among GLP-1 receptor agonist users, 552 [28·0%] were non-Hispanic White, 703 [35·7%] were non-Hispanic Black, and 568 [28·8%] were Hispanic. The 5-year unadjusted cumulative incidence of death-censored graft loss from a cohort matched on survival time before GLP-1 receptor agonist initiation was 6·0% for GLP-1 receptor agonist users and 10·7% for non-users (Gray's test p=0·004). The 5-year unadjusted cumulative incidence for mortality from a cohort matched on survival time before GLP-1 receptor agonist initiation was 17·0% for GLP-1 receptor agonist users and 25·8% for non-users (log-rank p=0·0006). The 5-year unadjusted cumulative incidence for mortality was 13·5% for GLP-1 receptor agonist users and 19·9% for non-users (log-rank p<0·0001). GLP-1 receptor agonist use was associated with a 49% lower incidence of death-censored graft loss (adjusted subhazard ratio [aSHR] 0·51, 95% CI 0·36-0·71; p=0·0001) and 31% lower mortality (adjusted hazard ratio [aHR] 0·69, 95% CI 0·55-0·86; p=0·001). Inferences were robust when matched on survival time (death-censored graft loss aSHR 0·53, 95% CI 0·37-0·75; p=0·0005; mortality aHR 0·70, 95% CI 0·55-0·88; p=0·003). Safety endpoints were rare and not associated with GLP-1 receptor agonists, with the exception of diabetic retinopathy (aHR 1·49, 1·11-2·00; p=0·008). INTERPRETATION/CONCLUSIONS:GLP-1 receptor agonists were associated with better graft and patient survival. Clinical trials are needed to confirm these findings. FUNDING/BACKGROUND:National Institutes of Health.

BACKGROUND:Bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) remains the gold standard for treating obesity. Most people regain weight from postsurgery nadir. OBJECTIVES/OBJECTIVE:Liraglutide 3.0 mg is approved for weight management. This study will examine the effects on liraglutide 3.0 mg on weight regain post-RYGB. SETTING/METHODS:University Hospital, United States. METHODS:A 56-week, double-blind, placebo-controlled study was conducted in 132 subjects, who achieved ≥25% total body weight loss (TBWL) status-post-RYGB and regained ≥10% TBWL after reaching nadir weight (NW). Subjects 18-120 months post-RYGB were randomized to receive liraglutide 3.0 mg/d (n = 89) or placebo (n = 43) with lifestyle counseling regularly for 56 weeks. The co-primary endpoints were the proportion of subjects losing at least 5%, 10%, and 15% TBWL and achieving weight lower than their NW. RESULTS:53.4% of the placebo group and 65% of the liraglutide group completed the trial due to Severe acute respiratory syndrome coronavirus 2 pandemic. The change in %TBWL from baseline to 56-weeks was -8.8 (8.5, -29.2 to 9.7) and 1.1 (3.5, -7.9 to 5.99) in the liraglutide and placebo groups, respectively. 76% and 17% of subjects achieved ≥5% TBWL at 56 weeks in the liraglutide and placebo groups, respectively; 51% and 26.0% of the liraglutide group achieved ≥10% and ≥15% TBWL, respectively. None of the placebo group lost ≥10% TBWL. Twenty-one percent of subjects receiving liraglutide surpassed postoperative NW. No subjects on placebo met this goal. Nonserious adverse events occurred in 41.6% of subjects on liraglutide. Serious adverse events (SAE) occurred less often on liraglutide. CONCLUSIONS:Liraglutide was significantly more effective than placebo in treating weight regain that occurs post-RYGB without increased SAE.

Highly effective antiobesity and diabetes medications such as glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide/GLP-1 (dual) receptor agonists (RAs) have ushered in a new era of treatment of these highly prevalent, morbid conditions that have increased across the globe. However, the rapidly escalating use of GLP-1/dual RA medications is poised to overwhelm an already overburdened health care provider workforce and health care delivery system, stifling its potentially dramatic benefits. Relying on existing systems and resources to address the oncoming rise in GLP-1/dual RA use will be insufficient. Generative artificial intelligence (GenAI) has the potential to offset the clinical and administrative demands associated with the management of patients on these medication types. Early adoption of GenAI to facilitate the management of these GLP-1/dual RAs has the potential to improve health outcomes while decreasing its concomitant workload. Research and development efforts are urgently needed to develop GenAI obesity medication management tools, as well as to ensure their accessibility and use by encouraging their integration into health care delivery systems.

Obesity is a public health crisis, with prevalence rates tripling over the past 60 y. Although lifestyle modifications, such as diet and physical activity, remain the first-line treatments, recent anti-obesity medications (AOMs) have been shown to achieve greater reductions in body weight and fat mass. However, AOMs also reduce fat-free mass, including skeletal muscle, which has been demonstrated to account for 20% to 50% of total weight loss. This can equate to ∼6 kg or 10% of total lean mass after 12-18 mo, a loss comparable to a decade of human aging. Despite questions surrounding the clinical relevance of weight loss-induced muscle loss, the importance of adopting lifestyle behaviors such as eating a protein-rich diet and incorporating regular resistance training to support skeletal muscle health, long-term weight loss maintenance, and overall well-being among AOM users should be encouraged. Herein, we provide a rationale for the clinical significance of minimizing weight-loss-induced lean mass loss and emphasize the integration of diet and physical activity into AOM clinical care. Owing to a lack of published findings on diet and physical activity supporting skeletal muscle health with AOMs, specifically, we lean on findings from large-scale clinical weight loss and diet and exercise trials to draw evidence-based recommendations for strategies to protect skeletal muscle. We conclude by identifying gaps in the literature and emphasizing the need for future experimental research to optimize skeletal muscle and whole-body health through a balance of pharmacotherapy and healthy habits.

OBJECTIVES/OBJECTIVE:Obesogenic medications are a putative contributor to the obesity epidemic. While 20% of adults take ≥1 obesogenic medication, the proportion in the end-stage kidney disease (ESKD) population-a group enriched for cardiometabolic complications-is unknown. Obesogenic medications may contribute to obesity and hamper weight loss efforts to achieve transplant listing. METHODS:Using 2017-2020 USRDS and Medicare claims, patients were identified as taking obesogenic medications if prescribed anticonvulsants, antidepressants, antidiabetics, anti-inflammatories, antipsychotics, and/or antihypertensives known to cause weight gain for ≥30 days in their first hemodialysis year. Ordinal logistic and Cox regression with inverse probability of treatment weighting were used to quantify obesogenic medications' association with body mass index (BMI) and listing, respectively. RESULTS:Among 271 401 hemodialysis initiates, 63.5% took ≥1 obesogenic medication. For those in underweight, normal weight, overweight, and class I, II, and III categories, 54.3%, 58.4%, 63.1%, 66.5%, 68.6%, and 68.8% took ≥1, respectively. Number of obesogenic medications was associated with increased BMI; use of one was associated with 13% increased odds of higher BMI (aOR [adjusted odds ratio] 1.14; 95%CI: 1.13-1.16; p < 0.001), use of three was associated with a 55% increase (aOR 1.55; 95%CI: 1.53-1.57; p < 0.001). Any use was associated with 6% lower odds of transplant listing (aHR [adjusted hazard ratio] 0.94; 95%CI: 0.92-0.96; p < 0.001). Within each BMI category, obesogenic medication use was associated with lower listing likelihood. CONCLUSIONS:Obesogenic medication use is common in ESKD patients-particularly those with obesity-and is associated with lower listing likelihood. Whenever possible, non-obesogenic alternatives should be chosen for ESKD patients attempting weight loss to achieve transplant listing.

Obesity is a chronic, relapsing disease that increases the risks of living kidney donation; at the same time, transplant centers have liberalized body mass index constraints for donors. With the increasing number of anti-obesity medications available, the treatment of obesity with anti-obesity medications may increase the pool of potential donors and enhance donor safety. Anti-obesity medications are intended for long-term use given the chronic nature of obesity. Cessation of treatment can be expected to lead to weight regain and increases the risk of comorbidity rebound/development. In addition, anti-obesity medications are meant to be used in conjunction with-rather than in replacement of-diet and physical activity optimization. Anti-obesity medication management includes selecting medications that may ameliorate any co-existing medical conditions, avoiding those that are contraindicated in such conditions, and being sensitive to any out-of-pocket expenses that may be incurred by the potential donor. A number of questions remain regarding who will and should shoulder the costs of long-term obesity treatment for donors. In addition, future studies are needed to quantify the degree of weight loss and duration of weight loss maintenance needed to normalize the risk of adverse kidney outcomes relative to comparable non-donors and lower weight donors.

Obesity is a growing public health crisis in the United States and is associated with a substantial disease burden due to an increased risk for multiple complications, including cardiovascular and metabolic diseases. As highlighted in this review, obesity disproportionately affects the African American population, women in particular, regardless of socioeconomic status. Structural racism remains a major contributor to health disparities between African American people and the general population, and it limits access to healthy foods, safe spaces to exercise, adequate health insurance, and medication, all of which impact obesity prevalence and outcomes. Conscious and unconscious interpersonal racism also impacts obesity care and outcomes in African American people and may adversely affect interactions between health care practitioners and patients. To reduce health disparities, structural racism and racial bias must be addressed. Culturally relevant interventions for obesity management have been successfully implemented that have shown benefits in weight management and risk-factor reduction. Strategies to improve health care practitioner-patient engagement should also be implemented to improve health outcomes in African American people with obesity. When managing obesity in African American people, it is critical to take a holistic approach and to consider an individual's social and cultural context in order to implement a successful treatment strategy.

BACKGROUND:Bariatric procedures are safe and effective treatments for obesity, inducing rapid and sustained loss of excess body weight. Laparoscopic adjustable gastric banding (LAGB) is unique among bariatric interventions in that it is a reversible procedure in which normal gastrointestinal anatomy is maintained. Knowledge regarding how LAGB effects change at the metabolite level is limited. OBJECTIVES/OBJECTIVE:To delineate the impact of LAGB on fasting and postprandial metabolite responses using targeted metabolomics. SETTING/METHODS:Individuals undergoing LAGB at NYU Langone Medical Center were recruited for a prospective cohort study. METHODS:We prospectively analyzed serum samples from 18 subjects at baseline and 2 months after LAGB under fasting conditions and after a 1-hour mixed meal challenge. Plasma samples were analyzed on a reverse-phase liquid chromatography time-of-flight mass spectrometry metabolomics platform. The main outcome measure was their serum metabolite profile. RESULTS:We quantitatively detected over 4,000 metabolites and lipids. Metabolite levels were altered in response to surgical and prandial stimuli, and metabolites within the same biochemical class tended to behave similarly in response to either stimulus. Plasma levels of lipid species and ketone bodies were statistically decreased after surgery whereas amino acid levels were affected more by prandial status than surgical condition. CONCLUSIONS:Changes in lipid species and ketone bodies postoperatively suggest improvements in the rate and efficiency of fatty acid oxidation and glucose handling after LAGB. Further investigation is necessary to understand how these findings relate to surgical response, including long term weight maintenance, and obesity-related comorbidities such as dysglycemia and cardiovascular disease.

Introduction: Non-alcoholic fatty liver disease (NAFLD) is present in 36-70% of women with polycystic ovary syndrome (PCOS). Both are highly prevalent in subjects with obesity. Androgen overproduction in PCOS promotes a pro-apoptotic environment and may contribute to NAFLD. Our objective was to examine the association between PCOS and NAFLD diagnosis and if PCOS is an independent predictor of advanced fibrosis in patients with NAFLD.
Method(s): In a single-center retrospective analysis of electronic medical records, 625 adult patients ( .18 years old) with a diagnosis of NAFLD from 2018-2019 were divided into 3 cohorts: a female study group with PCOS, female control group without PCOS, and a male control cohort, age-matched to the study group. PCOS diagnosis was based on established PCOS society criteria. Our primary outcome was to assess the stage of liver fibrosis, as defined by histology, Fibroscan, MR elastography, NAFLD fibrosis score (NFS), by the age of initial diagnosis. Additionally, demographic, laboratory and clinical parameters were analyzed to compare the three cohorts. Demographics were analyzed using ANOVA, Pearson's chi-squared, and Kruskal-Wallis methods. Linear regression modeling NAFLD score as a function of age of diagnosis was performed.
Result(s): A total of 625 subjects with NAFLD were seen. Of these, 21 met criteria for the female NAFLD/PCOS study group, 525 in the female NAFLD only control group, and 79 age-matched male subjects with NAFLD. The NAFLD/PCOS females study group were significantly younger than the other two cohorts at time of diagnosis of NAFLD, had the highest BMI of 38.4, highest AST/ALT ratio of 0.92, lowest albumin value of 4.03, highest percentage of patients with physical signs of the male cohort was associated with a 0.7 reduction in NFS compared to women with NAFLD only. Females with NAFLD demonstrate significant difference in the mean NFS and mean age of diagnosis compared to the other 2 groups, while females with both versus males with NAFLD did not (Image 1).
Conclusion(s): Females with PCOS significantly demonstrated NAFLD at an earlier age supported by positive physical and radiological signs, and worse NFS vs. males at the time of initial NAFLD diagnosis.