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The Skinny on Weight Loss Drugs

There is mounting evidence that meaningful weight loss can be achieved with pharmacotherapy, in tandem with diet and exercise.

This article was originally posted in the Montreal Gazette.

It would be nice if there were a magical way to lose weight. There isn’t, of course. Maintaining your body weight is hard enough and actually losing the weight you’ve gained is even harder. While much has been written about various diets, it’s not clear that one outperforms the others. Bariatric surgery offers up under-utilized but very impressive benefits, but the prospect of undergoing surgery, unfortunately, makes many people nervous, despite the overall low complication rate. What many people want is a simple medication that would magically help the pounds melt off. Amazingly, that may no longer be science fiction.

Medical research has spent decades trying to develop a medication to help with weight loss, though most early attempts were met with failure. An early candidate, Dinitrophenol, resulted in a spate of deaths before being taken off the market. Amphetamines, also popular for a while as a weight loss treatment, met a similar fate. What surprises many people is that Health Canada-approved weight loss medications actually do exist, but they are not widely prescribed for a variety of reasons, including side effects and relatively modest benefits.

The tide, however, is beginning to turn. The one obesity medication that does seem to have a rather substantial benefit is liraglutide. Though initially designed as a diabetes medication, it has been shown to help with weight loss even in people who do not have diabetes, when combined with changes in diet and exercise. Liraglutide belongs to a class of medications called GLP-1 receptor agonists. They have two main drawbacks that have limited their widespread use. One is cost. The other is that they are injectable medications and patients in North America are reluctant to contemplate anything involving needles and daily injections.

At least one of those issues has been at least partially overcome by some of the newer medications in that drug class, like semaglutide. As a weekly rather than daily injection, semaglutide is more convenient. It is also highly effective, with an average weight loss of just under 30 pounds in the 68-week STEP-1 trial. When it was compared head-to-head against liraglutide in the STEP-8 trial, semaglutide outperformed its chemical cousin in terms of weight loss and demonstrated that it is more effective and more convenient to administer.

Not to be outdone, a newer GLP-1 receptor agonist called tirzepatide seems to be raising the bar again. Also a weekly injection, it outperformed semaglutide last year in diabetic patients in the SURPASS-2 trial. But the exciting news is the preliminary results of the SURMOUNT-1 trial suggesting that even in patients without diabetes, it resulted in a remarkable average weight loss of 52 pounds over 72 weeks.

Such profound weight loss, if borne out in the final publication, would be massively impressive. However, the issue of cost remains and may keep it out of reach for many patients, given that it may not be covered by their drug insurance. Also, side effects are an issue and these medications can cause problems like nausea, vomiting, diarrhea and digestive system upset. When started at a low dose and slowly increased, the side effects are minimized and often mild. They are also contraindicated in patients with a history of thyroid cancer or pancreatitis.

But despite these limitations, there is mounting evidence that meaningful weight loss can be achieved with pharmacotherapy. Some may say that obesity is a lifestyle problem and should be treated with diet and exercise, not medications. But Type 2 diabetes is to some degree affected by diet and lifestyle and no one would consider withholding treatment from these patients. Also, medications and diet/exercise are not either/or propositions. You can, and should, do both in tandem. The problem was that up until recently, there were no good treatments available to help people lose weight. As that changes, our approach to weight loss must change with it.


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