Trial of restarting and tolerating metformin (TreatMet).

This randomized, double-blind, placebo-controlled, n-of-1 crossover study assessed whether metformin's side effects are reproducible in patients with a history of metformin intolerance. Participants completed up to four cycles of 2 weeks of metformin exposure and 2 weeks of placebo exposure. Participants completed surveys based on the Gastrointestinal Symptom Rating Scale and the Treatment Satisfaction Questionnaire for Medication. The primary hypotheses were that treatment satisfaction would be equal for placebo and metformin and that more than 30% of the study enrollees would be able to adhere to a higher dose of metformin 6 months after participation. Thirteen patients (all women, mean age 52.4 years) enrolled, three of whom were lost to follow-up or were non-adherent to study protocol. Metformin was associated with significantly lower global treatment satisfaction scores compared with placebo (39.58 vs. 53.75, P < .05 ) but participants could not distinguish metformin from placebo and did not report higher rates of gastrointestinal side effects on metformin. Two out of 10 participants adhered to a higher dose of metformin after trial completion. Metformin appears to have barriers to use beyond its classic gastrointestinal side effects.

The impact of food order on postprandial glycaemic excursions in prediabetes.

Data suggest that nutrient order during a meal significantly impacts postprandial glucose and insulin excursions in type 2 diabetes, while its effects in prediabetes have not been reported. Fifteen participants with prediabetes consumed the same meal on 3 days in random order: carbohydrate first, followed 10 minutes later by protein and vegetables (CF); protein and vegetables first, followed 10 minutes later by carbohydrate (PVF); or vegetables first followed by protein and carbohydrate (VF). Blood was sampled for glucose and insulin measurements at 0, 30, 60, 90, 120, 150 and 180 minutes. Incremental glucose peaks were similarly attenuated by >40% in the PVF and VF meal conditions compared with CF. The incremental area under the curve for glucose was 38.8% lower following the PVF meal order, compared with CF, and postprandial insulin excursions were significantly lower in the VF meal condition compared with CF. The CF meal pattern showed marked glycaemic variability whereas glucose levels were stable in the PVF and VF meal conditions. Food order presents a novel, simple behavioural strategy to reduce glycaemic excursions in prediabetes.

Percutaneous Gastrostomy Device for the Treatment of Class II and Class III Obesity: Results of a Randomized Controlled Trial.

OBJECTIVES: The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling. METHODS: In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0-55.0 kg/m2 were randomly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling (n=137; mean BMI was 42.2±5.1 kg/m2) or Lifestyle Counseling alone (n=70; mean BMI was 40.9±3.9 kg/m2). The co-primary end points were mean percent excess weight loss and the proportion of participants who achieved at least a 25% excess weight loss. RESULTS: At 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (±s.d.) of 31.5±26.7% of their excess body weight (12.1±9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5% of their excess body weight (3.5±6.0% total body weight) (P<0.001). A total of 58.6% of participants in the AspireAssist group and 15.3% of participants in the Lifestyle Counseling group lost at least 25% of their excess body weight (P<0.001). The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period. Serious adverse events were reported in 3.6% of participants in the AspireAssist group. CONCLUSIONS: The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone.

Is Obesity the New Hypertension? Parallels in the Evolution of Obesity and Hypertension as Recognized Disease States.

Obesity and hypertension are recognized disease states that share many similarities including complex physiology, therapeutic response to both lifestyle modification and pharmacotherapy, and the need for long-term management. Both were initially believed to be disorders of lifestyle rather than true disease entities, and initial efforts at developing medical and surgical therapies were criticized. Ultimately, both have proven to be amenable to treatments that control their underlying physiology. Both hypertension and obesity have complex pathophysiology involving multiple regulatory pathways that may require combination therapies in addition to lifestyle modification to reach therapeutic goals. While hypertension is now a mature field practiced widely in primary care with the availability of 127 antihypertensive drugs, the specialty of obesity medicine is still in its infancy and growing in terms of management and development of medications, devices, and minimally invasive surgical interventions. Although the medical antiobesity armamentarium is relatively limited at present to six FDA-approved drugs, the development of combination pharmacotherapies with lower doses of component agents has improved efficacy and tolerability. As we look to the future of obesity medicine, hypertension can be used as a template to educate the public, fund research, and develop further treatment strategies.

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.

The feasibility, acceptability, and usability of telehealth visits.

Background: Telemedicine is now common practice for many fields of medicine, but questions remain as to whether telemedicine will continue as an important patient care modality once COVID-19 becomes endemic. We explored provider and patients' perspectives on telemedicine implementation. Methods: Physicians from three specialties within the Department of Medicine of a single institution were electronically surveyed regarding their perceptions of satisfaction, benefits, and challenges of video visits, as well as the quality of interactions with patients. Patients were surveyed via telephone by the Survey Research Group at Cornell about participation in video visits, challenges encountered, perceived benefits, preferences for care, and overall satisfaction. Results: Providers reported an overwhelmingly positive experience with video visits, with the vast majority agreeing that they were comfortable with the modality (98%) and that it was easy to interact with patients (92%). Most providers (72%) wanted to have more telemedicine encounters in the future. Key factors interfering with successful telemedicine encounters were technical challenges and insufficient technical support. Overall, patients also perceived video visits very positively regarding ease of communication and care received and had few privacy concerns. Some (10%-15%) patients expressed interest in receiving more technical support and training. There was a gradient of satisfaction with telemedicine across specialties with patients receiving weight management reporting more favorable responses while patients with lymphoma expressed more mixed responses. Conclusion: Both providers and patients found telemedicine to be an acceptable and useful modality to provide or receive medical care. The principal barrier to successful encounters was technical challenges.

A Randomized Controlled Pilot Study of the Food Order Behavioral Intervention in Prediabetes.

(1) Background: Prior research in individuals with overweight/obesity and prediabetes or type 2 diabetes has shown that the ingestion of protein-rich food and non-starchy vegetables before concentrated carbohydrates (a carbohydrate-last food order) led to lower postprandial glucose excursions over 180 min, compared to eating the same foods in the reverse order. To expand upon this research, we sought to examine the feasibility and impact of carbohydrate-last food order behavioral intervention on glucose tolerance (GT), HbA1c, weight, and nutrient intake in adults with prediabetes in the real world over a 16-week span. (2) Methods: A total of 45 adults with overweight/obesity and prediabetes were randomized to receive 4-monthly standard nutritional counseling (C) or standard nutritional counseling plus carbohydrate-last food order counseling (FO) sessions (NCT# NCT03896360). (3) Results: The FO group decreased in body weight (-3.6 ± 5.7 lbs, p = 0.017), and trended toward lower HbA1c (-0.1 ± 0.2, p = 0.054). The C group weight trended lower (-2.6 ± 6.8 lbs, p = 0.102) without altering HbA1c (-0.03 ± 0.3, p = 0.605). GT was unchanged in both groups after 16 weeks. Changes in weight, HbA1c, and GT were similar between groups. Sensitivity analysis of pre-COVID participants showed significant weight loss in the FO group (-5.9 ± 5.3 lbs, p = 0.003) but not in C group (-1.0 ± 6.8 lbs, p = 0.608). After 16 weeks, the C group significantly reduced its daily intake of calories, fat, protein, and grains whereas the FO group increased its daily intake of vegetables and protein. There were 17 (94%) FO participants that reported high intervention adherence and 13 (72%) reported it was easy to eat protein/vegetables before carbohydrates. (4) Conclusions: A carbohydrate-last food order is a feasible behavioral strategy in individuals with prediabetes that improves diet quality, notably increasing protein and vegetable intake.

Interventional diabetology: the evolution of diabetes care in the XXI century.

It has been observed that bariatric surgery, in addition to its profound weight-reduction effects, leads to a durable resolution of type 2 diabetes. This supports the possibility that a cure for this disease may be obtainable, both by surgery as well as with drugs or devices that mimics the effects of surgery'. Elucidating the mechanisms underlying the beneficial effects of gastrointestinal surgery may also facilitate understanding of the elusive etiology of this condition. Current evidence supports a role for surgical interventions in the treatment algorithm of obese patients with type 2 diabetes, while a number of device-based gastrointestinal interventions are now being investigated as novel and less invasive alternatives. Interventional diabetology could be defined by the use and study of traditional surgical options and novel, gastrointestinal device- based interventions for diabetes. In this manuscript, we discuss how the introduction of interventional diabetology may shape the way we approach diabetes in the 21st century.

Tirzepatide: Does the Evidence to Date Show Potential for the Treatment of Early Stage Type 2 Diabetes?

Tirzepatide is a novel "twincretin" with glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide receptor agonist activity, which was recently approved by the Food and Drug Administration for the treatment of type 2 diabetes mellitus. In this review, we discuss preclinical and mechanistic human studies, which demonstrate improvements in insulin sensitivity and beta-cell function with the use of tirzepatide, as compared to placebo and glucagon-like peptide 1 receptor agonists. We then discuss SURPASS trials 1-5, which evaluated the safety and efficacy of tirzepatide for type 2 diabetes mellitus as either monotherapy or combination therapy with other antidiabetic agents. The magnitude of tirzepatide's effects and the efficacy relative to other anti-diabetes medications on weight, glycemic control, and beta-cell function may prove beneficial for the treatment of early type 2 diabetes mellitus. Further studies, including data on cardiovascular outcomes and long-term safety, will continue to elucidate the role of tirzepatide in the treatment algorithm of type 2 diabetes mellitus.

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.

Management of Weight Regain Following Bariatric Surgery: Behavioral Intervention and Pharmacotherapy.

INTRODUCTION: Bariatric surgery is the most effective intervention currently available for significant and durable weight loss, but weight regain after surgery is not uncommon. This paper focuses on updates in behavioral interventions and pharmacotherapy to combat weight regain after bariatric surgery. AREAS COVERED: This paper critically reviews both prospective and retrospective studies assessing pharmacotherapy in post-bariatric surgical patients published within the past 5 years. It also evaluates updates in behavioral therapies and delivery of the therapies in this patient population. EXPERT OPINION: Weight regain after bariatric surgery is common. Patients who experience weight regain should be evaluated and treated by a multidisciplinary team. Antiobesity pharmacotherapy should be considered for those who qualify as an adjunct to lifestyle modifications, along with behavioral interventions such as cognitive behavioral therapy.

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.

Medical weight management protects against weight gain during the COVID-19 pandemic.

Background: American adults have gained weight during the COVID-19 pandemic. Little is known about how patients who are medically managed for overweight and obesity, including patients who are prescribed antiobesity pharmacotherapy, have fared. Objective: To assess the COVID-19 pandemic's effect on weight, food choices, and health behaviors in patients receiving medical treatment for overweight or obesity. Methods: Adult patients treated at an urban academic weight management center between 1 May 2019 and 1 May 2020 were electronically surveyed between 23 February and 23 March 2021. The survey assessed changes in weight, eating, behaviors, and the use of antiobesity medications (AOMs) following issuance of social distancing/stay-at-home policies in March 2020. Results: In 970 respondents, median percent weight change for those taking AOMs was -0.459% [interquartile range -5.46%-(+3.73%)] compared to +2.33% [IQR -1.92%-(+6.52%)] for those not taking AOMs (p < 0.001). More participants achieved ≥5% weight loss if they were taking AOMs compared to those who were not (26.7% vs. 15.8%, p = 0.004), and weight gain ≥5% was also lower in those taking AOMs (19.8% vs. 30.3%, p = 0.004). Patients with pre-pandemic BMI ≥30 kg/m2 taking AOMs experienced the greatest weight reduction, and there was greater weight loss associated with increased physical activity. Conclusions and Relevance: Medical weight management protected against weight gain during this period of the COVID-19 pandemic. Increased physical activity, decreased alcohol intake, and use of AOMs were factors that contributed to this protective effect.

Literature review on antiobesity medication use for metabolic and bariatric surgery patients from the American Society for Metabolic and Bariatric Surgery Clinical Issues Committee.

The following literature search is in response to inquiries made to the American Society for Metabolic and Bariatric Surgery (ASMBS) regarding antiobesity medication (AOM) use in patients who are having or have already had metabolic and bariatric surgery (MBS). These recommendations are based on current clinical knowledge, expert opinion, and published peer-reviewed scientific evidence available at this time. This paper is not intended to establish a local, regional, or national standard of care. The paper will be revised in the future as additional evidence becomes available.

Use of Weight Loss Medications in Patients after Bariatric Surgery.

PURPOSE OF REVIEW: Weight regain after bariatric surgery is unfortunately a common occurrence. In this article, we have reviewed the data addressing this clinical problem focusing on pharmacological management of weight regain. RECENT FINDINGS: Data from several small, non-randomized, retrospective, and prospective studies provide evidence that a number of pharmacological options, both FDA approved and off-label, are effective in mitigating and managing weight regain after bariatric surgery. There is a suggestion that the optimal time to initiate weight loss medications may be at the time of weight plateau, rather than after weight regain. Adjuvant pharmacotherapy can help treat weight regain after bariatric surgery. Future studies should investigate the optimal timing for starting weight loss medications, as well as the best medication or combinations of medicines, for managing postoperative weight regain in different patient groups, including those who have undergone different types of bariatric surgeries.

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.

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.