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Weight Loss Wonder Drug or Dangerous Fad? The Truth About GLP-1 Agonists (Ozempic or Wegovy)



With the remarkable ability to promote rapid weight loss while managing blood sugar levels, these groundbreaking medications have quickly become the talk of the town.


What are GLP-1 Weight Loss Drugs?

GLP-1 (glucagon-like peptide-1) is a hormone that regulates blood sugar levels and appetite. GLP-1 weight loss drugs are medications that mimic the effects of GLP-1 to promote weight loss. These drugs work by slowing down digestion, reducing appetite, and increasing feelings of fullness.


Novo Nordisk is the manufacturer of both Ozempic and Wegovy, which are similar medications but approved for different uses. Ozempic, a 1 mg semaglutide injection, has been FDA-approved for treating diabetes since 2017, and a higher 2 mg dose was approved in early 2022. Wegovy, on the other hand, is a higher dose of semaglutide (2.4 mg) that was approved in July 2021 specifically for treating obesity.


GLP-1 Agonists: Are They Really "Miracle Drugs" for Weight Loss?

Clinical trials have demonstrated the impressive weight loss effects of GLP-1 agonists, but what are the impacts of these drugs on body composition? While shedding excess fat mass can be beneficial for health, losing lean mass can be associated with poorer health trajectories and reduced lifespan.


Not all Weight Loss is Healthy

Losing excess fat mass can have a multitude of beneficial effects on health. Shedding lean mass – including muscle and bone density – is associated with poorer health outcomes. Safe and effective obesity treatments are those that significantly reduce fat mass while minimizing the concurrent loss of lean mass. While a certain amount of lean loss is inevitable with significant weight reduction, the goal is to increase the body’s overall proportion of lean mass.


The Truth About GLP-1 Agonists and Your Body Composition

Though clinical trials have generated impressive data on the weight loss effects of GLP-1 agonists, body composition has not been included among primary endpoints for these larger studies. Body composition metrics are considered safety endpoints which require far smaller cohorts for testing. Investigations into body composition changes on GLP-1 agonists are thus limited and likely underpowered.


From the information available on early, smaller studies, GLP-1 agonists appear to cause an alarming proportion of lean mass loss. In the STEP 1 trial (2021) and a substudy of the SUSTAIN 8 trial, a significant amount of weight loss was due to lean mass loss, with approximately 39% and nearly 40% of total weight loss being lean mass, respectively.


Is Weight Loss Worth the Risk? Who Should Think Twice About GLP-1 Agonists

While lean mass loss among individuals with obesity can still be an acceptable cost for dramatic weight reduction, GLP-1 agonists have grown in popularity as a weight loss drug among healthy-weight individuals, a trend that should raise concern.


Although fat loss can be beneficial for individuals with obesity, the potential benefits of fat loss for healthy-weight individuals are minimal and are unlikely to offset the sizable health risks associated with reduced lean mass. Furthermore, since the only large-scale trials of GLP-1 agonists have been conducted in obese or overweight study populations, we don’t yet know if these drugs affect body composition in normal-weight individuals in an equivalent manner.

Even among patients with obesity, not all can afford to lose significant lean mass. Sarcopenic obesity, which is especially common in older populations, is characterized by the dual hazards of excess fat mass and low levels of skeletal muscle. Further reductions in lean mass among those with too little to begin with could pose a greater threat to health and longevity than the presence of excess fat.


Caution

While GLP-1 agonists may be effective in reducing body weight, the downsides on body composition cannot be ignored. Overweight or obese patients may still benefit from GLP-1 agonists, despite the potential for lean mass loss. For patients without excess fat, the considerable risk of lean mass loss just doesn’t seem worth the benefits. Patients with sarcopenic obesity, characterized by low levels of skeletal muscle and excess fat mass, may be at greater risk of health complications if they experience further reductions in lean mass. For patients with sarcopenic obesity, alternative weight loss strategies such as bariatric surgery may be a more promising option. Even for patients with obesity and sufficient lean mass, efforts should still be made to minimize lean mass loss as much as possible. This can include increasing weight-bearing exercise and strength training to counteract losses in muscle and bone mass while taking these drugs, and ensuring sufficient protein intake.

Conclusion

While GLP-1 agonists have been celebrated for their potency in reducing body mass, it’s important to remember that there are no miracle drugs. The downsides on body composition cannot be ignored, and both physicians and patients ought to exercise caution and discretion in determining the right weight management strategy.


FAQs

Q: What are GLP-1 receptor agonists?

A: GLP-1 receptor agonists are a class of medications used for the treatment of type 2 diabetes and obesity. They work by mimicking the action of the incretin hormone glucagon-like peptide-1 (GLP-1), which stimulates insulin secretion and suppresses appetite.

Q: What are the names of the GLP-1 agonists available in the US?

Q: How do GLP-1 agonists work?

Q: Are GLP-1 agonists effective for weight loss?

Q: What are the risks of lean mass loss?

Q: Are there any alternative weight loss strategies for patients with sarcopenic obesity?

Q: I am already taking a GLP-1 receptor agonist, what can I do to mitigate muscle loss?







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