Will Ozempic Help with Weight Loss?

Obesity has become a global epidemic, with over 650 million adults worldwide considered obese. This is a staggering figure, and the health consequences are severe, including increased risk of diabetes, heart disease, stroke, and certain cancers.

As a result, many people are now pursuing a healthier lifestyle, chasing weight loss and fat loss.

Pharmaceutical companies have been racing to develop effective medical treatments to help people lose weight and keep it off. Two of the most promising new drugs are semaglutide (brand names Ozempic and Wegovy) and tirzepatide (brand name Mounjaro).

In this blog post, we’ll take an in-depth look at how these medications work, their benefits and risks, and whether they could be an appropriate weight loss tool when combined with lifestyle changes.

Understanding How Semaglutide and Tirzepatide Work

Both semaglutide and tirzepatide belong to a class of drugs called GLP-1 receptor agonists. They work by mimicking a hormone called glucagon-like peptide-1 (GLP-1) that is released naturally in the body after eating. GLP-1 is a profound appetite suppressant that slows digestion and suppresses appetite by signaling satiety and fullness to the brain.

Semaglutide and tirzepatide bind to and activate GLP-1 receptors, which enhances this effect. Ozempic and Wegovy are injectable formulations of semaglutide, while Mounjaro is an oral formulation of tirzepatide.

That’s the science of it, but here’s what you need to know: The end result is that a person feels fuller sooner after eating, stays feeling full longer between meals, and experiences an overall substantial reduction in hunger and appetite. This can naturally leads to eating less without feeling deprived or hungry all the time.

In addition, GLP-1 receptor agonists slow gut motility, meaning food passes more slowly through the digestive tract, which also prolongs feelings of fullness.

The Clinical Trial Results

In large clinical trials, both semaglutide and tirzepatide have been shown to produce significant weight loss in participants. For example, in the SURMOUNT-1 trial, tirzepatide led to average weight reductions of 49 pounds at the highest studied dose. Semaglutide trials demonstrated average losses of 12-15% of body weight.

These results are far superior to what has been seen in studies of other weight loss medications, like Contrave or Saxenda. Part of this enhanced efficacy likely stems from the fact that semaglutide and tirzepatide more potently activate GLP-1 receptors compared to earlier drugs in this class. The newer formulations deliver the active drug more efficiently so that it lingers longer in the body.

Benefits Beyond Weight Loss

In addition to weight loss, semaglutide and tirzepatide provide other meaningful health benefits:

Blood Glucose Benefits

• Improved blood glucose control and A1c levels for those with type 2 diabetes or prediabetes due to improved glycemic control

Improved Lipid Profile

• Lower triglycerides and LDL cholesterol

Improved Cardio Health

• Decreased blood pressure

Improved Hepatic Health

• Reduced liver fat content

These effects translate into reduced cardiovascular and metabolic disease risk for those taking the medication. For example, the SURMOUNT-1 trial found that tirzepatide cut the risk of major cardiovascular events, like heart attack and stroke, by 49% compared to placebo.

Potential Side Effects to Consider

As with any potent medication, semaglutide (ozempic) and tirzepatide do come with potential side effects that need to be considered:

• Nausea – The most common side effect, experienced by around 20% of people, especially when first starting treatment. This usually improves over days to weeks.
• Diarrhea – Can also occur as the drug slows gut motility. May improve over time.
• Vomiting – More common with higher doses.
• Gallbladder issues – A low risk of gallstones or inflammation requiring removal of the gallbladder.
• Pancreatitis – There have been rare cases of pancreatitis reported. Risk factors like history of pancreatitis or very high triglycerides may increase chances.
• Hypoglycemia – Possible in those with diabetes concurrently using insulin or sulfonylureas, since the medications lower blood sugar.
• Drug interactions – Semaglutide may delay gastric emptying, which could impact absorption of other oral medications taken at the same time. While studies did not show clinically significant interactions with warfarin, digoxin, atorvastatin or metformin, further research is needed, especially for drugs with a narrow therapeutic index like levothyroxine or warfarin. Patients on these types of medications should be closely monitored and timed appropriately apart from semaglutide dosing.
• Loss of muscle mass – Dr. Peter Attia, a physician and renowned longevity expert, has used GLP-1 agonists like ozempic and mounjaro in his clinical practice for years. Through extensive experience with patients on these medications, he has raised serious concerns about excessive loss of muscle mass if protein intake is not sufficient and strength training is not maintained. At his practice, Dr. Attia monitors body composition and sets clear guidelines on acceptable muscle loss rates. He emphasizes the importance of patients prioritizing adequate protein consumption and resistance training routines to preserve lean mass while on GLP-1 drugs. The goal is healthy fat loss, not breakdown of metabolic muscle. With diligence on lifestyle factors, medications and training can work synergistically for optimal body composition improvements under medical supervision.
• Thyroid C-cell tumors – Ozempic carries an FDA boxed warning about potential thyroid C-cell tumor risk based on rodent studies, although this risk has not been confirmed in humans or nonhuman primates. Patients with a personal or family history of certain thyroid tumors should discuss this potential risk with their doctor before starting treatment. While unproven in humans, the boxed warning advises caution until more data is available. However, these findings have not been found in nonhuman primates or in humans.
• Unknown long-term risks – As newer drug formulations, the long-term safety profile of semaglutide (ozempic) and tirzepatide beyond 1-2 years of use is not yet fully characterized. The clinical trials establishing their efficacy for obesity involved relatively short-term administration. There is insufficient data to predict the effects of being on these medications for many years or decades, as would be necessary for lifelong obesity treatment. Potential concerns include unknown effects on organs like the pancreas and gallbladder over time. There are also questions around the durability of weight loss effects in the long run and whether efficacy is maintained or patients develop tolerance. Each person must carefully weigh the unknowns around taking any new biological agent for an extended period of time. A thorough discussion of the long-term risk-benefit ratio with one’s medical provider is advised. Close monitoring and proactive management of side effects is also prudent.

Who Should Consider These Medications?

Given the powerful weight loss but potential side effects, who are the best candidates for GLP-1 drugs like semaglutide or tirzepatide? The Obesity Medicine Association guidelines recommend these medications for:

• Those with a BMI of 30 or higher (or 27-29 with an obesity-related condition like diabetes or hypertension)
• Those who have tried first-line lifestyle interventions like improving nutrition and increasing activity without success
• Those who do not have specific medical contraindications, like a personal or family history of certain endocrine tumors called MTC or MEN-2
• Those who have prediabetes or type 2 diabetes that need to be brought under better control
• Those who understand and accept the potential risks and side effects
• Those who will use the medication as an adjunct to making positive lifestyle changes long-term

The Challenges of Maintaining Weight Loss

These GLP-1 agonist show some real promise for weight loss, but there are concerns.

Dr. Peter Attia, drawing on his extensive clinical expertise, has also raised concerns about the sustainability of weight loss on GLP-1 drugs. He has seen many patients regain a significant portion of their lost weight after discontinuing these medications. This pattern highlights the limitations of a purely pharmaceutical approach for long-term weight management. While medications can produce dramatic short-term results, maintaining weight loss over decades requires continuing lifestyle interventions, habit change, and support even after stopping the drugs. The development of new, healthy habitual behaviors and combating ingrained drivers of overeating is a lifelong endeavor that medication alone cannot accomplish. Dr. Attia’s experience demonstrates the vital importance of taking a holistic, multipronged approach that goes far beyond any single pill or injection if the goal is permanent, sustainable weight reduction.

The Brain Science of Why Old Habits Persist

Unfortunately, these medications on their own often don’t offer a long-term solution.

Neuroscientist Dr. Andrew Huberman has delved into why it can be so hard to change our habitual behaviors, even if we consciously want to. His research has uncovered the powerful role that neuroplasticity plays.

Neuroplasticity refers to the brain’s ability to structurally rewire itself and form new neural connections through repetition and practice. Unfortunately, neuroplasticity can work against us too – engraining unhealthy habitual behaviors over years to the point that they become extremely challenging to overcome.

As Dr. Huberman explains, the basal ganglia structures deep in the brain reinforce and perpetuate habits through literal physiological changes to neurons and synapses. So even if hunger is lessened with medication, there is still a deeply rutted neurological habit pattern driving unhealthy food choices. New habits require carving new neurological pathways, which doesn’t happen overnight.

Going Beyond Appetite Suppression Alone

While semaglutide and tirzepatide powerfully suppress appetite and lead to significant weight reduction, we do have to ask – is blocking hunger signals the only answer?

According to behavioral science, many of our habitual eating behaviors are not actually driven by physical hunger in the first place. We eat out of habit, boredom, for emotional regulation, as a social lubricant, for reward and pleasure, or simply due to food availability and cues in our environment. The reasons are multifactorial and go far beyond just hunger alone.

At HBI, we use the acronym EATS to summarize the four major root causes of behavior: Escape, Attention, Tangible, and Sensory. We eat to escape or avoid negative emotions or situations. We eat to get attention from others. We eat to obtain tangible rewards like pleasure or satisfaction. And we eat for sensory stimulation – because food tastes, smells, or feels good.

So while medications like semaglutide and tirzepatide can help eliminate excess eating driven specifically by hunger signals, they don’t necessarily address the other complex drivers of unhealthy eating patterns summarized by EATS. This is why behavior change interventions need to go hand in hand with pharmaceutical approaches. And this is why at HBI we endorse and teach a course on applying behavioral science strategies to fitness coaching, to help people overcome ingrained habits.

The Multipronged Approach: Meds Plus Lifestyle Change

Given this science, taking semaglutide or tirzepatide alone is unlikely to lead to long-term weight loss success without also addressing the habitual behavioral patterns through coaching, smart lifestyle strategies, and support.

As an example, a person may notice they always stop for a pastry and coffee on the way to work out of habit and anticipation of reward. While semaglutide may curb their hunger at breakfast, the baked good is not actually driven by hunger in the first place. Without also adopting a new routine – like having a protein shake at home instead – the old habit will likely persist.

Similarly, someone who eats chips and snacks mindlessly in the evenings while watching TV is not eating just because they are hungry. The medication will blunt physical hunger but not the force of this ingrained habit. With support to recognize their true root causes and cues, and the creation of a new routine that fulfills the same root cause like having tea or going for an evening walk, they can start to break the old pattern.

The Missing Piece

When taking potent medications like semaglutide or tirzepatide for weight loss, it’s critical to also understand the behavioral science behind why we eat. As discussed earlier, the four root causes of behavior can be summarized by the acronym EATS – Escape, Attention, Tangible rewards, and Sensory stimulation.

While medications can suppress appetite and hunger signals, they don’t address the habitual behaviors driven by EATS. For example, someone may eat out of boredom in the evenings while watching TV. Even if ozempic curbs their physical hunger pangs, the act of mindlessly snacking could still persist out of sheer habit.

Likewise, when stopping weight loss medications, understanding EATS helps explain why weight regain often occurs. The person may have developed some new habits while taking the drug, but the old habitual drivers can creep back in. Without continued vigilance and lifestyle strategies to keep EATS tendencies in check, falling back on old overeating patterns is all too easy.

This is why a multipronged approach is so critical for long-term weight management. Medications like semaglutide target the biological signals, while behavioral interventions target the ingrained habits of EATS. Using both in tandem gives the best chance of breaking unhealthy eating cycles for good. When stopping medications, maintaining lifestyle changes and being mindful of EATS instincts is key to keeping lost weight off.

Cautions for Healthy Weight Individuals

While semaglutide and tirzepatide can produce substantial fat loss in those with obesity, leading to significant health improvements, the use of these drugs in normal weight populations warrants more caution.

Individuals who do not have excess body fat are unlikely to derive meaningful benefits from further fat reduction. However, they may face heightened risks from the medications’ effects on lean mass and muscle loss. Since non-overweight individuals have less fat mass to begin with, the proportion of weight loss coming from muscle breakdown could be even higher.

This lean mass depletion is concerning because maintaining strong muscles and an optimal strength-to-fat ratio is a key predictor of health and longevity. The minimal fat reduction benefits do not appear to outweigh the downsides of impaired body composition for normal weight persons.

Unfortunately, despite these risks, GLP-1 drugs have gained popularity among some non-obese individuals primarily interested in further weight loss or body sculpting for aesthetic reasons. However, it is not clear whether the research trials establishing safety and efficacy included many non-obese participants or can be extrapolated to lean populations.

More data is urgently needed on the impacts of semaglutide and tirzepatide specifically in normal weight individuals before the use of these potent medications can be considered appropriately safe and justified in non-obese demographics. Any normal weight persons considering these drugs would be wise to have an in-depth discussion of both benefits and risks with their medical provider.

Given the current state of evidence, the Obesity Medicine Association maintains that GLP-1 medications are most appropriately prescribed for those with obesity or overweight accompanied by obesity-related conditions. For now, non-obese individuals are best advised to optimize body composition through evidence-based nutrition, strength training, cardio exercise, and lifestyle approaches for ideal health.

The Bottom Line

Semaglutide and tirzepatide represent exciting new options for combating obesity by capitalizing on appetite-regulating hormone pathways in the body. For many people struggling with excess weight and related health conditions, these medications could provide substantial benefit when combined with lifestyle changes. However, their effects must be carefully monitored, and patients should take steps to minimize reductions in lean mass.

There is still much unknown about the long-term safety and efficacy of these new drugs. Those without obesity should exercise extreme caution before considering these medications, as the risks likely outweigh the minimal benefits. Each individual must carefully weigh the potential benefits and risks with their medical team.

While powerful tools, medications alone are unlikely to be a panacea without also applying proven behavioral strategies to eat less and optimize lifestyle. Those battling obesity have the best chances of success using a multipronged approach that addresses physiology, habits and environments. While the path may not be easy, it is navigable and brighter days lie ahead.