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Are We Entering a Golden Era of Anti-Obesity Medications?



I have been practicing medicine long enough to remember treating hypertension before there were ACE inhibitors or ARBs. I vividly remember training in a lipid clinic before the introduction of statins. Many will recall managing type 2 diabetes before we had TZDs, DPP4 inhibitors, SGLT2 blockers, or GLP-1 analogues. 

In all of these disease areas, prior to the introduction of the currently available effective medications, the focus was on dietary and other behavioural interventions.  Thus, I recall giving talks on sodium restriction, physical activity, or the DASH diet for managing hypertension or on the AHA Step I/II diets to manage dyslipidemia. While dietary and other behavioural interventions remain important pillars for managing these conditions, it would be quite uncommon today to see clinicians manage any of these entities with “lifestyle” interventions alone. 

However, the latter is still the case for treating obesity, which in itself remains the exception rather than the rule as far as clinical management is concerned.

This may be about to change. 

Thus, according to a paper by Timo Müller and colleagues, published in Nature Reviews Drug Discovery, there is much reason for hope that we will soon have a plethora of anti-obesity medications that may well drastically change obesity management.

The paper extensively reviews the rather sketchy past history of anti-obesity medication and provides a brief primer on the complex neuroendocrine systems that govern the energy homeostasis. 

The authors also highlight the important challenges in developing effective anti-obesity medications including heterogeneity of the disorder, the complexity of the neuroendocrine system, translating findings from animals to humans, and of course safety aspects. 

The authors then go on to discuss the various existing and potential targets with an update on the rather wide range of molecules currently under investigation. Broadly, these can be classified as incretin-based (mono-, dual- and even triple-agonists), leptin, leptin-sensitisers and MC4 receptor agonists, mitochondrial uncouplers, GDF15, amylin, PYY, and a few others. 

While no one expects all or even most of these molecules to ultimately meet the rather high bar of efficacy and safety, one would have to be rather pessimistic to think that none of these molecules will make it. 

Rather, as we are currently witnessing with the recent regulatory approval of semaglutide for obesity (in the US, UK, EU and Canada), which is promising to deliver weight-loss in the 15-20% range, and the emerging data for the dual agonist tirzepatide or the early data for the combination of semaglutide with the amylin analogue cagrilinitide, it is foreseeable that medical treatment of obesity will one-day routinely involve the use of anti-obesity medications, in the same way that medications are routinely used to manage hypertension, dyslipidemia or type 2 diabetes.

Obviously, much needs to happen before this becomes a reality. Not only do we need long-term outcome studies (some of which are already underway) but we also need payors to help make these medications accessible to those who need them. Finally, we need education of both health care providers and patients to fully understand why these medications are necessary in the first place and how they can be best used to reduce the burden of obesity related complications and impairments in quality of life in people living with obesity. 

@DrSharma

Berlin, D

1 Comment

  1. Dr. Sharma,

    Thank you for today’s article. It gives more hope to those suffering with obesity, myself being one of them.

    I recently attended the Weight Wise Clinic in Edmonton with a starting weight of 292 lbs. I was able to lose 37 lbs through LifeStyle changes and interventions provided by the clinic but then my weight stalled. This was a 13% weightloss.

    I was still 255 lbs and as I wanted to lose more. I then started Saxena generic name: Liraglutide for more weight loss. I have managed to get down to 225 ish. and so that is a further 30 lbs lost with a new total of 67 lbs lost. This is a total percentage now of 23% total weightloss. I realize this weightloss is probably as much as I can expect to lose even with the medication but I continue to work towards keeping the weight off and possibly losing more. I accept that this weight might be where my body has decided to sit.

    I am so thankful for the obesity drugs. However, as you said, a major problem is will the payor’s pay for this. Up until now my extended coverage paid for this drug. But as I am now retired, next year the Saxenda alone is more than my yearly maximum, so I am unsure how I can continue. And if/when I move out of Alberta, my pension plan health benefits will not be transferable so I will get no compensation. I know that stopping the medication means I’ll probably gain some of the weight back that I’ve lost on the drug and am afraid of gaining weight once I have to stop.

    The Saxenda has allowed me to lose enough weight to be able to move better, walk further, play with my grandkids, be able to get up and down from the floor more easily and just generally feel better. I am also no longer prediabetic!
    When I have to stop the drug because its no longer covered, I am at risk for once again becoming prediabetic, then diabetic, unable to walk much, difficulty climbing stairs, unable to get up and down like I need to for my grandchildren and gardening etc. Going off of Saxenda is counterintuitive to me staying mobile but the cost makes continuing very difficult.

    What can we as individuals on these drugs do to help convince Drug payor’s to pay for these drugs?

    Sincerely,
    Rosemary Dinsdale

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