Progression from prediabetes to type 2 diabetes mellitus in adolescents: a real world experience.

Background: Obesity in pediatric patients is strongly associated with increased vascular and metabolic risk. Prediabetes is present in up to 1 in 5 adolescents, aged 12-18 years-old, though is thought to remit spontaneously in a significant portion. Pediatric patients with type 2 diabetes mellitus (T2D) have a more rapid decline of beta-cell function and progression to treatment failure than adult T2D patients. Thus, there is a strong interest in better understanding the natural history of prediabetes in these youth. We aimed to evaluate the real-world rate of progression of prediabetes to T2D in adolescent patients. Methods: This is a retrospective study of 9,275 adolescent subjects aged 12-21 years-old with at least 3 years of de-identified commercial claims data and a new diagnosis of prediabetes during the observation period. Enrollees with a T2D diagnosis and/or diabetes medication use in the 1 year prior to prediabetes diagnosis or a T2D diagnosis in the 1 month following prediabetes diagnosis were excluded. Enrollees with diagnoses of type 1 diabetes (T1D) or polycystic ovarian syndrome over the 3 years were also excluded. Progression to T2D was defined by claims data of two T2D diagnoses at least 7 days apart, HbA1c ≥ 6.5%, and/or prescription of insulin without known T1D. Enrollees were followed for 2 years after prediabetes diagnosis. Results: Overall, 232 subjects (2.5%) progressed from prediabetes to T2D. There were no differences found in T2D progression based on sex or age. Progression to T2D occurred at a median of 302 days after prediabetes diagnosis (IQR 123 to 518 days). This study was limited by the lack of laboratory/anthropometric data in administrative claims, as well as the exclusion of 23,825 enrollees for lack of continuous commercial claims data over 3 years. Conclusion: In the largest sample to date on adolescent prediabetes, we found a 2.5% progression of prediabetes to T2D over a median duration of about one year.

Five-year Weight Loss Maintenance With Obesity Pharmacotherapy.

CONTEXT: Long-term treatment of obesity with lifestyle changes alone is unsustainable for most individuals because of several factors including adherence and metabolic adaptation. Medical management of obesity has proven efficacy for up to 3 years in randomized controlled trials. However, there is a dearth of information regarding real-world outcomes beyond 3 years. OBJECTIVE: This work aimed to assess long-term weight loss outcomes over a 2.5- to 5.5-year period with US Food and Drug Administration (FDA)-approved and off-label antiobesity medications (AOMs). METHODS: A cohort of 428 patients with overweight or obesity were treated with AOMs at an academic weight management center with an initial visit between April 1, 2014, and April 1, 2016. Intervention included FDA-approved and off-label AOMs. The primary outcome was percentage weight loss from initial to final visit. Key secondary outcomes included weight reduction targets as well as demographic and clinical predictors of long-term weight loss. RESULTS: The average weight loss was 10.4% at a mean follow-up duration of 4.4 years. The proportions of patients who met the weight reduction targets of 5% or greater, 10% or greater, 15% or greater, and 20% or greater were 70.8%, 48.1%, 29.9%, and 17.1%, respectively. On average, 51% of maximum weight loss was regained, while 40.2% of patients maintained their weight loss. In a multivariable regression analysis, a higher number of clinic visits was associated with more weight loss. Metformin, topiramate, and bupropion were associated with increased odds of maintaining 10% or greater weight loss. CONCLUSION: Clinically significant long-term weight loss of 10% or more beyond 4 years is achievable in clinical practice settings with obesity pharmacotherapy.

Long-term weight loss maintenance with obesity pharmacotherapy: A retrospective cohort study.

Objective: To determine the association of anti-obesity medications (AOMs) with weight loss maintenance over 2 years. Methods: This is a retrospective observational cohort study of adults treated for obesity between 1 April 2014 and 1 April 2016 at a tertiary academic weight management center and who completed 2 years of follow-up. Main outcome measures were mean percent weight loss, percent of individuals who achieved clinically significant long-term weight loss (≥5% weight loss over 2 years), and long-term weight loss maintenance (achievement of ≥5% weight loss at 1 year and maintenance of the ≥5% reduction for the second year). Results: Of the 1566 new patients, 421 completed 1- and 2-year follow-up appointments. Patients were mostly female and on average 51 years old; they weighed 100.1 kg and had a BMI of 35.8 kg/m2 at initial visit. Mean weight losses at 1 and 2 years were 10.1% and 10.2%, respectively. The proportion of patients who experienced ≥5% weight loss was 75.5% at 1 year and 72.9% at 2 years. Long-term weight loss maintenance was achieved by 65.3% of patients. Almost all (96.2%) were on ≥1 AOM at 2 years, with metformin, phentermine, and topiramate among the most prescribed. AOM usage and older age demonstrated trends toward predicting weight loss maintenance over 2 years. Conclusions: Long-term weight loss maintenance was observed among adults with medically managed obesity who completed 2 years of follow-up.

Weight Loss Outcomes With Telemedicine During COVID-19.

Background: Amidst the COVID-19 pandemic, telemedicine was rapidly implemented to maintain patient care during quarantine. However, there is little data on how this transition may have impacted weight loss outcomes and interventions among patients with overweight or obesity. Methods: This was a retrospective observational study of adults who established care for medically managed obesity at the Weill Cornell Comprehensive Weight Control Center during September-November 2019 and May-July 2020 and who completed 6 months of follow-up. Weight loss outcomes and weight management interventions were explored and stratified by patient-provider interaction: in-person visits only, in-person and video visits, and video visits only. Results: Of 499 charts eligible for review, 245 (49%) returned for their 6-month follow-up visit and were included for analysis. Of 245 patients, 69 had in-person visits only ("in-person"), 85 started in-person and later switched to video visits ("hybrid"), and 91 had video visits only ("video"). All cohorts were predominantly white and female. Median ages were 56, 49, and 49 years; baseline median weights were 98.9, 96.8, and 93.0 kg; and baseline median BMIs were 35.3, 34.4, and 34.0 kg/m2 for in-person, hybrid, and video cohorts, respectively. The median percent weight changes over 6 months were not significantly different among cohorts: -4.3% [-8.5, -1.5] in the in-person cohort, -5.6% [-8.7, -2.2] in the hybrid group, and -5.8% [-9.7, -2.4] in the video cohort. The percent of patients who achieved ≥5% weight loss were also similar: 46.4%, 55.3%, and 59.3%, respectively. The median number of visits in the video cohort was more than in the in-person or hybrid groups (5 vs. 4). Median number of anti-obesity medications (AOMs) prescribed was similar among groups. The most common AOMs were metformin (all cohorts) followed by semaglutide 1.0 mg (in-person and video) or topiramate (hybrid). Conclusion: Patients on anti-obesity medications who were followed for 6 months via video or video plus in-person visits (hybrid) experienced clinically significant weight loss. Median number of AOMs were similar among groups, and the most common AOMs were metformin, semaglutide 1.0 mg, and topiramate. More investigation is required to compare telemedicine models with in-person care.

Pharmacologic management of weight regain following bariatric surgery.

While bariatric surgery restults in significant long-term weight loss for most patients with obesity, post-surgical weight gain affects a considerable percentage of patients to varying degrees of severity. Furthermore, a small but significant percentage of patients experience inadequate post-surgical weight loss. Although many studies have examined the role of anti-obesity medications to address post-operative weight regain, an evidence-based consensus has not yet been achieved because of the heterogeneity of populations studied and the studies themselves. Observational studies in the post-bariatric surgery population consistently demonstrate the benefit of medical weight management after bariatric surgery, with most evidence highlighting liraglutide, topiramate, and phentermine/topiramate. New anti-obesity medications are anticipated to be helpful for post-surgical weight optimization given their efficacy in the non-surgical population.

Obesity and Diabetes.

Obesity is the most significant risk factor for the development of diabetes. Both obesity and diabetes rates have continued to increase in tandem and pose increased mortality for patients and increased health care costs for the community. Weight loss of 5% or more of total body weight renders improvements in glycemic control, decreases in the need for diabetes medications, and improved quality of life. Cotreatment of obesity and diabetes requires a comprehensive medical approach that encompasses intensive lifestyle modification including behavioral changes, nutrition, and physical activity, as well as pharmacotherapy and possible surgical management.

Combined medical strategies for the management of type 2 diabetes mellitus and obesity in adults.

INTRODUCTION: Given the relationship between the pathogenesis of obesity and type 2 diabetes mellitus (T2DM) as well as their significant health consequences, treatment strategies that can induce weight loss while achieving glycemic control are needed. Novel weight-reducing anti-diabetic agents along with anti-obesity medications (AOMs) can help medical providers address both conditions simultaneously and effectively. AREAS COVERED: This review summarizes and compares weight loss efficacy and glycemic control of weight-reducing anti-diabetic medications, AOMs and emerging pharmacologic agents that help treat both obesity and T2DM. EXPERT OPINION: Management of obesity and T2DM can be challenging to achieve and sustain in the presence of obesogenic anti-diabetic agents. Utilizing weight-reducing anti-diabetic agents, AOMs, and endobariatric or surgical procedures, either separately or in combination, can help achieve better clinical outcomes in patients with obesity and T2DM. Some agents in development, such as tirzepatide and bimagrumab, are promising pharmacotherapy options that may change the standards of care for cardiometabolic disease management.

A Systematic Review of Dietary Supplements and Alternative Therapies for Weight Loss.

OBJECTIVE: Dietary supplements and alternative therapies are commercialized as a panacea for obesity/weight gain as a result of the minimal regulatory requirements in demonstrating efficacy. These products may indirectly undermine the value of guideline-driven obesity treatments. Included in this study is a systematic review of the literature of purported dietary supplements and alternative therapies for weight loss. METHODS: A systematic review was conducted to evaluate the efficacy of dietary supplements and alternative therapies for weight loss in participants aged ≥18 years. Searches of Medline (PubMed), Cochrane Library, Web of Science, CINAHL, and Embase (Ovid) were conducted. Risk of bias and results were summarized qualitatively. RESULTS: Of the 20,504 citations retrieved in the database search, 1,743 full-text articles were reviewed, 315 of which were randomized controlled trials evaluating the efficacy of 14 purported dietary supplements, therapies, or a combination thereof. Risk of bias and sufficiency of data varied widely. Few studies (n = 52 [16.5%]) were classified as low risk and sufficient to support efficacy. Of these, only 16 (31%) noted significant pre/post intergroup differences in weight (range: 0.3-4.93 kg). CONCLUSIONS: Dietary supplements and alternative therapies for weight loss have a limited high-quality evidence base of efficacy. Practitioners and patients should be aware of the scientific evidence of claims before recommending use.

Preadmission predictors of severe COVID-19 in patients with diabetes mellitus.

OBJECTIVE: To explore predictors of severe COVID-19 disease in patients with diabetes hospitalized for COVID-19. METHODS: This is a retrospective observational study of adults with diabetes admitted for COVID-19. Bivariate tests and multivariable Cox regression were used to identify risk factors for severe COVID-19, defined as a composite endpoint of intensive care unit admission/intubation or in-hospital death. RESULTS: In 1134 patients with diabetes admitted for COVID-19, more severe disease was associated with older age (HR 1.02, p<0.001), male sex (HR 1.28, p=0.017), Asian race (HR 1.34, p=0.029 [reference: white]), and greater obesity (moderate obesity HR 1.59, p=0.015; severe obesity HR 2.07, p=0.002 [reference: normal body mass index]). Outpatient diabetes medications were not associated with outcomes. CONCLUSIONS: Age, male sex, Asian race, and obesity were associated with increased risk of severe COVID-19 disease in adults with type 2 diabetes hospitalized for COVID-19. SUMMARY: In patients with type 2 diabetes hospitalized for COVID-19 disease, we observed that age, male sex, Asian race, and obesity predicted severe COVID-19 outcomes of intensive care unit admission, intubation, or in-hospital death. The risk conferred by obesity increased with worsening obesity. Outpatient diabetes medications were not observed to be significant predictors of study outcomes.

The Independent Risk of Obesity and Diabetes and Their Interaction in COVID-19: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to assess whether diabetes mellitus (DM) or obesity is an independent risk factor for severe coronavirus disease 2019 (COVID-19) outcomes and to explore whether the risk conferred by one condition is modified by the other. METHODS: This retrospective cohort study of inpatient adults with COVID-19 used multivariable Cox regression to determine the independent effects of DM and obesity on the composite outcome of intubation, intensive care unit admission, or in-hospital mortality. Effect modification between DM and obesity was assessed with a statistical interaction term and an exploration of stratum-specific effects. RESULTS: Out of 3,533 patients, a total of 1,134 (32%) had DM, 1,256 (36%) had obesity, and 430 (12%) had both. DM and obesity were independently associated with the composite outcome (hazard ratio [HR] 1.14 [95% CI: 1.01-1.30] and HR 1.22 [95% CI: 1.05-1.43], respectively). A statistical trend for potential interaction between DM and obesity was observed (P = 0.20). Stratified analyses showed potential increased risk with obesity compared with normal weight among patients with DM (HR 1.34 [95% CI: 1.04-1.74]) and patients without DM (HR 1.18 [95% CI: 0.96-1.43]). CONCLUSIONS: DM and obesity are independent risk factors associated with COVID-19 severity. Stratified analyses suggest that obesity may confer greater risk to patients with DM compared with patients without DM, and this relationship requires further exploration.

An update on pharmacotherapeutic strategies for obesity.

INTRODUCTION: The field of obesity medicine has evolved over the past several years. With greater understanding of its pathophysiology, obesity is regarded more as a chronic disease than a lifestyle choice. However, it is difficult to treat with lifestyle modifications alone due to the complexity of energy dysregulation. The availability of anti-obesity medications (AOMs) provides practitioners with more effective and sustainable ways to treat obesity. AREAS COVERED: This review briefly summarizes the weight loss efficacy of AOMs currently approved for long-term use and expands on their therapeutic potential beyond weight loss with particular focus on obesity-related comorbidities. Possible future AOMs with promising phase II or III data are also covered. EXPERT OPINION: The future of obesity medicine is in recognizing obesity as a disease and approaching treatment similarly to other chronic diseases. Lifestyle interventions alone are rarely sufficient in the treatment of chronic diseases, and pharmacotherapy often plays a necessary role in changing the course of disease. Current AOMs have proven efficacy in weight management and emerging therapeutic uses in obesity-related comorbidities, such as non-alcoholic fatty liver disease, obstructive sleep apnea, and polycystic ovarian syndrome. The development of new AOMs will further empower providers to deliver effective obesity management.

Metformin-induced weight loss in patients with or without type 2 diabetes/prediabetes: A retrospective cohort study.

It is unknown whether weight loss outcomes differ with metformin monotherapy in patients with obesity with or without type 2 diabetes (T2DM)/prediabetes (PreDM). In this retrospective study, 6- or 12-month weight loss outcomes were compared in 222 patients with or without T2DM/preDM who completed metformin monotherapy. Average weight loss was similar between groups, euglycemic vs. T2DM/preDM (6 months: 6.5 [6.0%] vs. 6.5 [6.1%] p = 0.97; 12 months: 7.4 [6.2%] vs. 7.3 [7.7%], p = 0.92). Categorical weight losses (≥5% and ≥10% of baseline weight) were also similar. Comparable clinically significant weight loss was achieved with metformin monotherapy in patients with obesity with or without T2DM/PreDM.

Best Practices in the Management of Overweight and Obesity.

Obesity is a chronic disease caused by dysregulated energy homeostasis pathways that encourage the accumulation of adiposity, which in turn results in the development or exacerbation of weight-related comorbidities. Treatment of obesity relies on a foundation of lifestyle modification; weight loss pharmacotherapy, bariatric surgery and devices are additional tools to help patients achieve their health goals. Appropriate management of patients with obesity provides multiple metabolic benefits beyond weight loss.

Medical Weight-Loss Outcomes in Patients Receiving Concomitant Psychotropic Medication: A Retrospective Cohort Study.

OBJECTIVE: This study aimed to elucidate medical weight-loss outcomes in patients unexposed or exposed to psychotropic medication(s). METHODS: This retrospective cohort study evaluated weight-loss outcomes of completers treated at an academic weight-management center between April 1, 2014, and April 1, 2016. Patients were classified as either unexposed (not prescribed psychotropic medication) or exposed (prescribed psychotropic medication) based on use of antidepressants, mood stabilizers, or antipsychotics during the study. RESULTS: Of 1,932 patients seen during the study period, 885 were eligible for inclusion, of whom 619 (70.0%) were unexposed and 266 (30.0%) were exposed to psychotropic medications. In the unexposed and exposed groups, the mean age, sex distribution, proportion with type 2 diabetes, initial BMI, and number of weight-loss medications prescribed were similar. At 12 months, the unexposed group lost 1.6% more weight on average than the exposed group (9.1% [SD 7.6%] vs. 7.5% [SD 8.1%], respectively; P = 0.02); 71.0% and 41.2% of the unexposed group achieved ≥ 5% and ≥ 10% weight loss at 12 months, respectively, compared with 63.1% and 31.8% in the exposed group at 12 months (P = 0.04 at 5%; P = 0.02 at 10%). CONCLUSIONS: Exposure to psychotropic medications was associated with diminished weight loss in patients with medically managed overweight and obesity.

Surgical and Nonsurgical Weight Loss for Patients with Obstructive Sleep Apnea.

A strong association exists between excess weight and obstructive sleep apnea (OSA), and most patients with OSA have elevated body mass index. Weight loss is an essential part of treatment for patients with OSA and overweight or obesity. Lifestyle interventions are cornerstones of weight management. However, most patients have difficulty achieving and maintaining clinically significant weight loss with lifestyle interventions alone. Health care providers who treat patients with OSA should be familiar with advanced treatment options for overweight and obesity including antiobesity medications, bariatric surgery, and devices. The future of weight management is a customized, multidisciplinary approach for each patient.

An up-to-date evaluation of lorcaserin hydrochloride for the treatment of obesity.

Introduction: Obesity is a chronic disease caused by dysfunctional neurohormonal systems that result in excess weight, adiposopathy, and increased risk for many comorbidities including cardiovascular disease, type 2 diabetes, and certain types of cancer. Lorcaserin is a serotonergic agonist specific to the 5HT2C receptor that is FDA-approved for the long-term management of obesity in adults with BMI>30 kg/m2 or BMI>27 kg/m2 and at least one weight-related comorbidity.Areas covered: The authors review the pharmacodynamics and pharmacokinetic properties of lorcaserin alongside updates on serotonin's mechanism of action in the central nervous system. The efficacy of lorcaserin in the management of obesity, its related comorbidities, and potential therapeutic applications are also discussed.Expert opinion: The future of obesity management requires a multimodal and personalized approach. The high medical complexity of patients warrants polypharmacotherapy to achieve their metabolic goals. Lorcaserin has proven efficacy and safety in the treatment of obesity and its weight-related comorbidities including type 2 diabetes, cardiovascular disease, and chronic kidney disease. New evidence elucidating its effects on dopaminergic pathways and on glucose homeostasis expands its prospective uses.

Long-Term Modulation of Appetitive Hormones and Sweet Cravings After Adjustable Gastric Banding and Roux-en-Y Gastric Bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) produces greater weight loss compared with a purely restrictive procedure such as laparoscopic adjustable gastric banding (LAGB). OBJECTIVE: The objective of this study was to quantify changes in hormones that regulate energy homeostasis and appetitive sensations before and after LAGB (n = 18) and RYGB (n = 38) in order to better understand the mechanisms underlying the greater weight loss after RYGB. METHODS: A standardized test meal was administered prior to surgery, at 6 months, and annually thereafter to year 2 after LAGB and year 4 after RYGB. Blood samples were obtained in the fasted state and 30, 60, 90, and 120 min post-meal. RESULTS: Progressive increases in fasting PYY were observed after RYGB together with increases in postprandial area under the curve (AUC) levels that were unchanged after LAGB. GLP-1 AUC increased only after RYGB. There was a weight loss-related increase in fasting ghrelin levels after LAGB that was unchanged 1 year after RYGB despite greater percentage weight loss; ghrelin subsequently increased at years 2-4 post-RYGB. HOMA-IR decreased after both procedures but correlated with weight loss only after LAGB, whereas leptin correlated with weight loss in both groups. Sweet cravings decreased after RYGB. CONCLUSION: A number of weight loss-independent changes in the gut hormonal milieu likely act in concert to promote a decrease in insulin resistance and greater weight loss efficacy after RYGB. A progressive change in hormone levels over time may reflect gut enteroplasticity after RYGB. A decrease in sweet cravings specific to RYGB may further promote superior weight loss outcomes.

Metreleptin and generalized lipodystrophy and evolving therapeutic perspectives.

INTRODUCTION: Metreleptin was recently approved by the Food and Drug Administration for the treatment of generalized lipodystrophy, a condition characterized by leptin deficiency. Its efficacy as hormone replacement therapy suggests broader applications in diseases also characterized by leptin abnormalities, such as familial partial lipodystrophy (FPLD), non-alcoholic fatty liver disease (NAFLD), and common obesity. Metreleptin, in conjunction with other pharmacologic interventions, has the potential to address one of the most widespread epidemics of our time, obesity. AREAS COVERED: This review covers the physiology of leptin, the pharmacologic properties of recombinant methionyl human leptin (R-metHu-Leptin, metreleptin), evidence for metreleptin's efficacy in the treatment of generalized lipodystrophy from both completed and ongoing clinical trials, safety concerns, and future directions in metreleptin research. EXPERT OPINION: Metreleptin's approval for generalized lipodystrophy is the first step in defining and expanding its role to other metabolic diseases. Clinical trials are underway to delineate its efficacy in FPLD, human immunodeficiency virus/highly active anti-retroviral therapy-associated acquired lipodystrophy (HAL), and NAFLD. Additionally, there is growing data that support a therapeutic role in obesity. One of the barriers to development, however, is metreleptin's safety and immunogenicity. Further advances in biologic compatibility are required before metreleptin can be approved for additional indications.