Obesity and Weight Loss
Novel and Emerging Therapies for Obesity
Temporary Surgical Procedures/Endosleeves
The duodenojejunal bypass sleeve (DJBS) is a flexible, nutrient-impermeable plastic sleeve that is surgically inserted into the upper part of the small intestine (duodenum). The sleeve serves as a barrier to nutrient absorption, simulating the effect of a Roux-en-Y gastric bypass, but is a reversible procedure (Gersin 2007). By preventing absorption in the part of the small intestine closest to the stomach, the sleeve may also delay gastric emptying and stimulate satiety (Nguyen 2012a). DJBSs are temporary devices for weight loss; in human trials they were left in place for 3 months and successfully removed, resulting in the loss of 22-24% of excess weight. Complications include esophageal tears, bloating, upper gastrointestinal bleeding, and movement of the sleeve (Nguyen 2012a).
Metformin, a first-line anti-diabetic drug with a long history of safety and efficacy, has shown promising results as an anti-obesity therapy. While not currently approved for weight loss, studies have shown average weight losses between 4.4 and 6.6 pounds, reaching up to 19.8 pounds in some studies. Metformin also has the added benefit of being known to prevent progression to diabetes in pre-diabetic patients (Garber 2012). Metformin may also reduce the activity of inflammatory cytokines; low-grade inflammation is associated with the incidence of metabolic disorders (eg, obesity and diabetes) (Molavi 2007; Buler 2012). Finally, metformin can produce many of the gene expression changes associated with long-term caloric restriction in animal models, possibly due to its influence on insulin or IGF-1 signaling (Dhahbi 2005).
Acarbose (Precose®) is an oral anti-diabetic agent that delays glucose release from complex carbohydrates by inhibiting the activity of the enzyme alpha-glucosidase, and can lead to a reduction of post-meal blood glucose levels (Hanefeld 2004). Two comprehensive reviews of more than 30 randomized, double-blind, placebo-controlled trials with a minimum acarbose treatment course of 12-weeks have shown its ability to significantly improve glycemic control and lower glycated hemoglobin (HbA1c) in type 2 diabetic patients (Van de Laar 2005). The first of the 2 analyses (7 acarbose studies) (Hanefeld 2004) demonstrated lower triglyceride levels and systolic blood pressure in the acarbose treatment group, and a significant effect on reducing the risk of heart attack and other cardiovascular events. Across these studies, there was a slight average reduction in body weight of 2.4 pounds among type 2 diabetic patients on acarbose therapy, compared to 1.8 pounds for the placebo group; BMI data also showed a similar modest reduction with acarbose treatment. In the second review (Van de Laar 2005), the weight-lowering effects of acarbose were not clinically significant.
Researchers have identified a natural fiber called alpha-cyclodextrin that selectively absorbs and eliminates bad fats such as trans fat or saturated fat while leaving good fats like omega-3s untouched to deliver their benefits. This remarkable molecule binds up to nine times more dietary fat from the intestinal tract in comparison with other fibers. Unlike conventional dietary fiber, which non-selectively binds fat in about a 1:1 ratio, a single gram of alpha-cyclodextrin is able to bind up to approximately 9 grams of fat (Jen 2013).
Moreover, alpha-cyclodextrin has been shown to selectively reduce unhealthy fats while leaving alone the safer fats. In a compelling confirmatory experiment, rats were fed diets containing alpha-cyclodextrin or control supplements and then given a test diet with radioactively labeled saturated or unsaturated fats. The result was a seven-fold increase in excretion of saturated fats in those given alpha-cyclodextrin compared with control animals. And there was no increase in excretion of the beneficial polyunsaturated fats like omega-3s in the alpha-cyclodextrin group (Gallaher 2007).
Studies showed if alpha-cyclodextrin were taken three times daily during high-fat meals (2 g per meal), it could engulf as much as 2 ounces of trans fat and saturated fat each day, which represents up to 500 calories of pure fat that never gets absorbed into the bloodstream (Jen 2013).