On the surface, the formula for weight loss seems simple: eat less and move more.
But giving that advice to someone with obesity is like telling someone with depression to cheer up.
Weight loss isn’t easy, or we wouldn’t be facing a crisis in overweight and obesity.
Our biology drives us to eat more food when it’s available, and our bodies have helped prepare us for times when we can’t find food by storing excess energy as fat.
Today, inexpensive, calorie-rich food is more abundant than in our hunter-gatherer past, and many of us consume as many calories as we like.
As a result, the fat that may have once helped us to survive has now become a threat — one we are only beginning to manage.
This change in food abundance has all happened in the last 100 years or so — an evolutionary blink of an eye.
Helpful medications
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It is unlikely humans will ever adapt for us not to gain weight, so when a class of drugs makes it possible to lose weight and keep it off, it’s a welcome and helpful development.
Though we are now seeing several new iterations of the class of drugs known scientifically as Glucagon-like peptide 1 receptor (GLP-1R) agonists (you may know them under such names as Ozempic, Wegovy, Saxenda or Zepbound), these types of drugs have actually been around for about 20 years, having started their useful life as treatments for Type 2 diabetes.
Claiming Science magazine’s breakthrough of the year in 2023, these drugs are an absolute revelation: they give you long-lasting weight loss as long as you continue taking them.
The drugs aren’t quite as effective as bariatric surgery, but they’re not far off, and they do the job without surgery. These drugs may become as good as bariatric surgery at controlling weight long-term.
Such drugs have proven to be so popular — even as injectables and at a price that makes them challenging for some users to afford — that there have been shortages as manufacturers try to expand production to meet growing demand.
All of this, at least superficially, is welcome news since overweight and obesity increase the risk of many other health issues, including certain cancers and cardiovascular disease.
People using these drugs are reporting not only losing weight but also having more energy and greater mobility, which, again, are welcome outcomes.
That said, it’s important to exercise caution and prudence about what else this first generation of GLP-1R agonists might mean for our bodies over time.
Fat loss and muscle loss
Losing weight by dieting (restricting energy) includes, along with fat loss, losing lean mass, about half of which is typically muscle. The general rule is that three-quarters of what we lose is fat and the rest is lean tissue.
My research focuses on the positive health outcomes of maintaining muscle, especially as we age and become more susceptible to sarcopenia, the steady age-related loss of muscle mass.
In our research work, my colleagues and I use our findings to encourage everyone to exercise, and particularly to include resistance training — load-bearing exercise with the aim of gaining or at least maintaining muscle mass and strength.
Losing muscle can have a significant, direct effect on our quality of life. We need strength to reduce the risk of falls and muscle to reduce the risk of metabolic diseases such as Type 2 diabetes, which in older age can have severe outcomes.
So, while losing weight is an excellent way to improve our health, it should bear the caveat of not losing muscle, especially in older persons.
Exercise and protein
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There is no doubt this newly recognized class of weight-loss drugs is a watershed discovery and could improve lives for generations to come.
If, as we see from early clinical trials, these drugs promote the loss of lean mass together with the loss of fat, it will be important for users to be aware and for pharmaceutical companies to adjust future generations of these drugs.
Without deliberate efforts to exercise for strength and to increase their protein intake to retain muscle, there could be consequences.
The body starts losing muscle after about age 40 to 45. By the time we’re in our 60s, 70s and 80s, these losses are noticeable.
Let’s look at a hypothetical example featuring a 60-year-old person who is obese with 45 per cent body fat and weighs 100 kilograms (220 pounds). If that person loses 20 kilograms (44 pounds) in one year while taking a GLP-1R agonist — which is not unreasonable while taking such drugs — then somewhere between 2.5 and three kilograms (5.5 to 6.5 pounds) could be muscle.
Such a loss may be consequential, especially when we consider that the same 60-year-old would lose, due to aging, about 0.3 kilograms (less than one pound) of muscle in one year.
Does the good of the weight loss outweigh the “bad” of the muscle loss? It’s still too early to know if muscle loss while taking GLP-1R agonists will be problematic in the long run, but I think it’s important to proceed with caution, especially in older persons, until trial results are available.
Stuart Phillips is a Professor and Canada Research Chair at McMaster University. He has patents licensed to Exerkine, which is a company that produces dietary supplements but reports no financial gains. He receives funding from NSERC, CIHR, the US NIH, and Industry sources.
