Off-label drugs for weight management

Abstract

The global pandemic of obesity and overweight now affects between 2.8 and 3.5 billion of the world population and shows no signs of abatement. Treatment for what is now recognized as a chronic disease includes pharmacotherapy, considered an essential component of comprehensive therapy. New drug discovery is robust, but the pace of the US Food and Drug Administration approval for obesity drugs has been glacial, and only a handful of approved drugs are available for treating obesity. In the last 20 years, the US Food and Drug Administration has approved 208 drugs for cancer, 118 for cardiovascular diseases, 168 for neurological diseases, and 223 endocrinologic drugs, but only 6 for obesity, 2 of which have been taken off market. Currently, there are only 9 drugs approved by the FDA for obesity treatment. US physicians have turned to off-label drug use in their effort to care for increasing numbers of patients with excess adiposity. Phentermine is the most commonly used drug for treating obesity. Although approved only for short-term use, US physicians have used it successfully for long-term since its initial approval in 1959. This drug, used off-label for long-term, has proven to be safe and effective, far safer than the disease it is used to treat. Phentermine and diethylpropion, an equally safe but somewhat less effective drug, are both generic and therefore inexpensive. These drugs have been maligned inappropriately because their two-dimensional structure diagrams resemble amphetamine and also because of unproven presumptions about their potential adverse effects. In the face of an increasing epidemic, worldwide obese and overweight patients deserve effective treatment that prescribing these drugs could provide, if rehabilitated and used more frequently. US physicians will likely continue to use any drug proven useful off-label for this illness until such time as more effective drugs are approved.

RSSDI-ESI clinical practice recommendations for the management of type 2 diabetes mellitus 2020

“…Metformin is the first choice drug with some evidence for weight loss. [ 635 636 ] The DPP and Indian Diabetes Prevention Program (IDPP) trial report that metformin and lifestyle intervention greatly reduce the risk of T2DM in overweight or obese patients. [ 637 ] Use of GLP-1receptor agonists,[ 254 ] SGLT-2 inhibitors,[ 255 638 ] and to some extents DPP-4 inhibitors[ 257 258 ] have been shown to induce weight loss and should be considered as add-on to metformin in obese T2DM patients.…”

Gewichtsänderung als unerwünschte Arzneimittelwirkung

“…Ein solcher "Off-label"-Missbrauch ist z. B. für Methylphenidat gut dokumentiert [17,18]. Bei der Indikationsstellung, aber auch wenn ein bestimmtes Arzneimittel von PatientInnen direkt nachgefragt wird, ist besondere Sorgfalt erforderlich.…”

Topiramate-related adverse events

“…[ 26 ] The precise mechanism by which topiramate leads weight loss remains unclear but appears to induce appetite suppression and increased energy expenditure. In the USA, topiramate has been used off-label for obesity patients both as a monotherapy and in combination with other drugs; [ 19 ] the combination of phentermine and topiramate (Qsymia) was approved for use in obesity. [ 4 ] In contrast, European Medicines Agency refused the marketing authorization for phentermine/topiramate (Qsiva) owing to its AEs.…”