Montreal Gazette

The skinny on weight loss medication­s

There is mounting evidence in favour of certain drugs

- CHRISTOPHE­R LABOS Christophe­r Labos is a Montreal physician and co-host of the Body of Evidence podcast.

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 underutili­zed 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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