Rekha B. Kumar

Endoscopic Sleeve Gastroplasty Significantly Reduces Body Mass Index and Metabolic Complications in Obese Patients

BACKGROUND & AIMS Endoscopic sleeve gastroplasty (ESG) is an incisionless, minimally invasive bariatric procedure that reduces the length and width of the gastric cavity to facilitate weight loss. We performed a prospective study to evaluate the effects of ESG on total body weight loss and obesity‐related comorbidities. METHODS We collected data from 91 consecutive patients (mean age, 43.86 ± 11.26 years; 68% female) undergoing ESG from August 2013 through March 2016. All patients had a body mass index (BMI) greater than 30 kg/m2 and had failed noninvasive weight‐loss measures or had a BMI greater than 40 kg/m2 and were not considered as surgical candidates or refused surgery. All procedures were performed with a cap‐based flexible endoscopic suturing system to facilitate a triangular pattern of sutures to imbricate the greater curvature of the stomach. Patients were evaluated after 6 months (n = 73), 12 months (n = 53), and 24 months (n = 12) for anthropometric features (BMI, weight, waist circumference, blood pressure) and underwent serologic (hemoglobin A1c), lipid panel, serum triglycerides, and liver function tests. The primary outcomes were total body weight loss at 6, 12, and 24 months. Secondary outcomes were the effects of ESG on metabolic factors (blood pressure, diabetes, hyperlipidemia, steatohepatitis) and safety. RESULTS The patients’ mean BMI before the procedure was 40.7 ± 7.0 kg/m2. Patients had lost 14.4% of their total body weight at 6 months (80% follow‐up rate), 17.6% at 12 months (76% follow‐up rate), and 20.9% at 24 months (66% follow‐up rate) after ESG. At 12 months after ESG, patients had statistically significant reductions in levels of hemoglobin A1c (P = .01), systolic blood pressure (P = .02), waist circumference (P < .001), alanine aminotransferase (P < .001), and serum triglycerides (P = .02). However, there was no significant change in low‐density lipoprotein after vs before ESG (P = .79). There was one serious adverse event (1.1%) (perigastric leak) that occurred that was managed non‐operatively. CONCLUSIONS ESG is a minimally invasive and effective endoscopic weight loss intervention. In addition to sustained total body weight loss up to 24 months, ESG reduced markers of hypertension, diabetes, and hypertriglyceridemia.

Pharmacotherapy for Obesity

Successful treatment of obesity requires a multidisciplinary approach including diet, exercise and behavioral modification. As lifestyle changes are not sufficient for some patients, pharmacologic therapies should be considered as adjuncts to lifestyle interventions. In this article, we review clinical indications, mechanisms of action, dosing/administration, side effects, drug interactions and contraindications for the six most widely prescribed obesity medications. We also summarize the efficacy data from phase 3 trials which led to drug approval. As multiple agents are sometimes required for clinically significant weight loss, the future of obesity medicine will likely involve combinations of agents in addition to behavioral counseling.

Lorcaserin Hcl for the treatment of obesity

Introduction: Obesity is a major health priority necessitating safe and effective strategies to address the obesity epidemic. Lorcaserin is a serotonergic agonist specific to the 5HT 2C receptor approved for chronic management of obesity in patients with a BMI ≥ 30 kg/m2 or a BMI ≥ 27 kg/m2 with comorbidities related to obesity. Areas covered: In this paper, the pharmacodynamic and pharmacokinetic properties of lorcaserin are reviewed followed by a discussion of efficacy and safety data from major clinical trials. Expert opinion: Lorcaserin is a unique highly selective serotonergic agonist designed to mitigate the risks associated with previous agents in this class. At therapeutic doses, it is well tolerated and produces modest but clinically meaningful weight loss with significant improvement in cardiometabolic parameters. Therapeutic efficacy should be assessed at 12 weeks (≥ 5% weight loss) to identify responders who will derive maximum weight loss and metabolic benefit from long-term therapy. The results of the ongoing cardiovascular outcomes trial (CAMELLIA TIMI 61) will determine the role of lorcaserin in primary prevention of diabetes in overweight/obese individuals and its use in the high-risk population of patients with established cardiovascular disease or multiple cardiovascular risk factors.

Practical Use of Pharmacotherapy for Obesity

Obesity management requires a multidisciplinary approach, as there are many factors that contribute to the development of obesity, as well as the preservation of excess weight once it has been gained. Diet, exercise, and behavior modification are key components of treatment. In addition to lifestyle changes, weight gain secondary to medications is an important modifiable risk factor. Even after appropriate lifestyle modification, and medication adjustments (where possible) to avoid agents that can contribute to weight gain, many patients are still unable to achieve clinically meaningful weight loss. Pharmacotherapy for obesity management can fill an important role for these patients. This article will review medications that can lead to weight gain and potential alternatives, currently approved anti-obesity medications and best practices to individualize the selection process, and the use of testosterone in men with hypogonadism and obesity.

Efficacy comparison of medications approved for chronic weight management.

For the first time, patients who are obese are able to benefit from 5 different FDA approved pharmacologic agents for chronic weight management. Although weight loss from all of these medications was limited to 5% to 10% of total body weight loss in the Phase III clinical trials, patients are capable of losing more weight when a cumulative approach of diet, exercise, and multiple medications are used. A pilot study of adding phentermine to lorcaserin yielded double the weight loss than lorcaserin alone. A higher percentage of total body weight is lost with use of combination phentermine/topiramate compared to orlistat, lorcaserin, and bupropion/naltrexone but there are more contraindications to its use and potential cardiovascular adverse effects due to adrenergic agonism. Lorcaserin and bupropion/naltrexone yielded similar weight loss but carry different adverse effect profiles and interactions with other psychiatric medications may preclude use of one over the other. When choosing a medication for obesity, several factors need to be considered, such as comorbidities, medication interactions, and risk of potential adverse effects.

Hypothalamic Inflammation: Is There Evidence for Human Obesity?

With increasing awareness of the obesity epidemic have come research efforts to understand the pathophysiology of body weight and appetite regulation. Clinical trials of diet-induced weight loss demonstrate the difficulty of achieving long term success in obese and overweight individuals, leading investigators to examine the question of what mechanisms makes weight loss so difficult. This has lead to a greater focus on neurologic and hormonal reasons that could explain why maintenance of lost weight is so challenging. Injury to the hypothalamic areas known to play a role in feeding and body weight regulation is being studied. Mechanisms of hypothalamic injury include increased inflammation, gliosis/scarring, and apoptosis of anorexigenic neurons in rodent models of diet induced obesity. Although there is evidence of hypothalamic damage due to interference of cell signaling and eventual loss of weight regulating neurons in rodent models, there is limited data thus far on whether we can apply this mechanism of injury to human obesity.

Current and Future Medical Treatment of Obesity

Obesity is a major health crisis resulting in comorbidities such as hypertension, type 2 diabetes, and obstructive sleep apnea. The need for safe and efficacious drugs to help assist with weight loss and reduce cardiometabolic risk factors is great. With several FDA-approved drugs on the market, there is still a great need to develop long-term obesity treatments or noninvasive oral agents to help assist individuals with obesity when used in conjunction with lifestyle modifications.

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.

Effect of Food Order on Ghrelin Suppression

Data suggest that the temporal sequence of carbohydrate ingestion during a meal has a significant impact on postprandial glucose (1–3), insulin, and glucagon-like peptide 1 (GLP-1) excursions (4) in type 2 diabetes, while the effects on ghrelin suppression and satiety have not been reported. The study design and methods have previously been described in detail (4). Briefly, using a crossover design, 16 subjects with overweight/obesity and metformin-treated type 2 diabetes were assigned to consume the same meal on 3 days in random order: Blood was sampled for glucose, insulin, active GLP-1, and total ghrelin measurements at baseline (just before meal ingestion) and at 30-min intervals up to 180 min. Participants rated their hunger and fullness levels using a visual analog …