Drug treatments for obesity
Peripheral Drugs
‘Peripherally acting anti-obesity drugs’ are another class of medication aimed at causing weight loss in overweight and obese individuals. These work by reducing the calorie intake from food, or altering the metabolism of it in the gastrointestinal system (gut). There is currently only one drug of this kind that is approved for use globally - Orlistat (Xenicol) - and it works by inhibiting the enzyme lipase that breaks down fat in the gut, meaning that the fat cannot be absorbed from food, and instead it is excreted out of the body.[R3]. Studies have shown that is can reduce the amount of fat absorbed from the gut by 30%, causing a decreased calorie intake and therefore weight loss. The weight loss from taking this medication is found to be between 5-10% on average.[R2][R6]. As well as weight loss, Orlistat has been shown to improve several other cardiovascular risk-factors. Low-density lipoproteins (LDL) and triglyceride levels were shown to be reduced by 10% more than expected for the weight loss, as well as blood pressure, waist circumference and lipids being reduced.[R2][R5]. Some research also suggests that Orlistat reduces fasting glucose and HbA1c levels in type 2 diabetics by more than predicted for the weight loss, with suggested methods including increased insulin sensitivity and glucagon-like peptide-1 secretion in the small intestine. Orlistat also helps to reduce the risk of type 2 diabetes in obese subjects by 37.3%. [R2].
However, this drug does not come without some side-effects. Oily-spotting, flatulence, abdominal cramps, faecal urgency/incontinence and liquid stools are the common adverse effects of Orlistat, due to an increase of fat in the gut and stools.[R3]. These side-effects are reported to only be experienced during the early stages, “but they subside as patients learn to use the drug”.[R4]. Orlistat also prevents some absorption of fat-soluble vitamins (A,E,D,K), and so patients are recommended to take supplements.[R3]. The drug does not have any systemic side-effects as it is contained in the gut, however it does affect the absorption of acyclovir, and they shouldn’t be used at the same time. [R4].
In 2001 the NHS National Institute for Health and Clinical Excellence (NICE) issued a press release on guidance for Orlistat use, and it states that it is cost effective to the NHS.[R8]. Studies have also shown that Orlistat is a cost-effective drug in obese adults.[R2].
As well as pharmaceutical drugs that work in the periphery to cause weight loss, there are also intrinsic chemicals produced in the body (hormones) that when released cause a feeling of satisfaction and being ‘full up’. These are called satiety signals. One example is Amylin, which is a hormone secreted along with insulin from the pancreas in response to a meal, causing you to feel full, therefore regulating your meal size. An amylin analogue, Pramlintide, is currently being looked into as a potential anti-obesity therapy, with it already being used in diabetics. Another example is glucagon-like peptide-1, which is released from the gut during eating, and relays satiety information to the brain via the vagus nerve. This is not yet approved, however, for obesity treatment. Another hormone secreted in the gut, peptide YY, could also be a potential for use, along with pancreatic polypeptide (PP) – both of which decrease appetite. Small-scale trials in a peptide called Oxyntomodulin have also been promising, with larger trials waiting to be preformed. [R5].