Is pharmacotherapy enough for urgent weight loss in severely obese patients?

The need for urgent weight loss can be defined as an imperative requirement of achieving a rapid and significant body weight reduction to get a prompt clinical improvement. Urgent body weight reduction may be required when obesity is associated with severe complications that can be attenuated by rapid and significant body weight reduction. This is the case for respiratory complications such as sleep apnea and hypoventilation syndrome, uncontrolled hypertension, hyperglycemia or dyslipidemia resistant to conventional therapy, incapacitating joint disease, presurgical weight reduction to diminish operative risks, including preparation for bariatric surgery, and treatment of severe weight regain. The question posed in the title refers to severe obesity that, as defined by a BMI> 40 kg/m, has not been widely tested in studies involving pharmacological obesity therapy. In those cases attention should be especially paid to obesity-related comorbidities as well as to the impact of weight excess on quality of life, which may also be severely affected in patients with lower BMI values. Significant caloric restriction represents a key factor to achieve a negative energy balance and hence, successful weight loss. In most cases the prescription of a very lowcalorie diet (VLCD) is an effective option to achieve a rapid improvement in sleep apnea, hypertension or type 2 diabetes control as well as a substantial preoperative weight loss to ensure an affordable operative risk [1]. In all these situations a 10% weight loss is usually followed by a significant clinical improvement. VLCD treatment for 6 weeks is associated with rapid weight loss, significant subcutaneous and visceral adipose tissue reduction as well as an improvement in liver fat content and insulin sensitivity [2]. As a consequence, glucose values improve as well as other complications such as hyperchylomicronemia, sleep apnea, hypertension or pulmonary insufficiency. In a presurgical scenario, a 4–13% BMI reduction can be achieved by VLCD treatment over 2–12 weeks [3], leading to a reduction of preoperative surgical risks. In general, VLCDs induce higher weight loss than low-calorie diets (LCDs) over three months of treatment [4], reaching up to 15–25% weight reduction [5]. However, therapy with a VLCD may be associated with some adverse effects such as alopecia, cold intolerance, constipation, electrolyte disorders, hypotension, or gallstone formation [5]. Moreover, VLCD use is contraindicated in the presence of cardiac arrhythmias, acute heart failure, psychiatric disorders, type 1 diabetes, liver and renal failure [1]. Although classically VLCDs are contraindicated in elderly patients, a recently published study shows that older obese adults treated with Optifast, a VLCD program, over three months experienced 11% weight loss with only 5% fatfree mass reduction [6]. Moreover, the adherence to a VLCD may be difficult to maintain, attrition reaching up to 22% [5]. Another concern regarding VLCDs is weight regain, which seems to be related to fat-free mass loss [7]. A complementary option to facilitate caloric restriction is represented by the use of endoscopic devices such as intragastric balloons (IGB) or duodenum-jejunal liners [3]. These devices are effective in the short-term to induce rapid weight loss but may also be associated with adverse effects that can lead to early removal, which in many cases is followed by significant weight regain.