Current State Of Anti-Obesity Medications: Introduction

In yesterday’s post, I argued for the need for safe and effective medications to better manage obesity.

I also noted that compared to medications for other chronic diseases like hypertension or diabetes, we are still in the early “pioneer” days of anti-obesity medications.

Nevertheless, in 2012, after a hiatus of nearly 13 years, the US-FDA approved two new anti-obesity drugs and is currently considering a third for approval.

In an invited review, published in Nature Endocrine Reviews, my colleagues Christian Rueda-Clausen, Raj Padwal  and I critically review the pharmacology, efficacy and safety profile of these new agents and discuss their use in the management of obesity.

In the introduction to this article we note that,

“Although the primary driver of weight gain is an imbalance between calorie intake and expenditure, lifestyle and behavioural interventions aimed at correcting this imbalance have limited long-term effectiveness.”

Not only are the lifestyle interventions for obesity characterized by high rates of recidivism or weight regain, but this is generally interpreted as further indication of the patients’ lack of will power.

This simplistic “blame-the-patient” reflex reflects nothing else than the rather limited understanding of most people (health professionals and regulators included) of the complex hormonal, metabolic and neurochemical changes associated with weight gain that result in powerful biological adaptations which both defend against subsequent weight loss and promote weight regain.

As we describe in our paper,

“These counter-regulatory adaptations include persistent changes in neurohormonal activation of appetite6 and marked reductions in resting and activity-related thermogenesis.”

It is this orchestrated biological response to weight loss (and not simply lack of motivation or will-power) that explains why the vast majority of individuals who lose weight as a result of “lifestyle” interventions alone ultimately fail to keep the weight off.

Thus,

“The primary aim of pharmacological treatment for obesity is to suppress the biological drivers of weight gain and/or dampen the counter-regulatory response to weight loss and thereby enable patients to achieve and sustain clinically meaningful reductions in body weight.”

Without doubt, the complexity and redundancy of the powerful neurohormonal systems that control hunger, appetite, satiety and other aspects of energy intake and metabolism make finding safe and effective medications challenging.

But these problems are not insurmountable and there is promise on the horizon.

In subsequent posts I will provide a brief summary of our review of the literature on new and emerging pharmacological treatments for obesity, which I hope will generate a healthy interest and discussion on these pages.

@DrSharma
Edmonton, AB

Rueda-Clausen CF, Padwal RS, & Sharma AM (2013). New pharmacological approaches for obesity management. Nature reviews. Endocrinology, 9 (8), 467-78 PMID: 23752772

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