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GLP-1 agonist medications have been a popular topic of discussion recently. While this weight loss drug was designed for obesity, GLP-1 agonists like Ozempic have made their way into Hollywood. This has people questioning their safety and possible health risks, especially in the long run. Are GLP-1 agonists a quick fix for weight loss or a lifetime prescription? Who should be prescribed this medication, and what are the possible side effects?
This Longevity by Design episode features an interview with Dr. Spencer Nadolsky—Medical Director of WeightW
Episode highlights
- Introduction: (0:00–2:00)
- Why Dr. Nadolsky became a physician: (2:00–4:13)
- What is cardiometabolic medicine?: (4:13–5:17)
- What is a “healthy” metabolism?: (5:17–7:37)
- How does diet impact glucose regulation: (7:37–10:20)
- Why has insulin resistance increased in the past decade?: (10:20–11:45)
- Ethnicity impacts BMI cutoffs: (11:45–12:57)
- Is obesity a choice?: (12:57–17:40)
- How socioeconomic status impacts obesity: (17:40–21:30)
- What's better: A BMI score or a DEXA scan?: (21:30–25:33)
- How strength training improves healthspan: (25:33–32:32)
- What a fasting insulin blood test tells you: (32:32–36:58)
- Health risks of insulin resistance: (35:15–38:08)
- How insulin resistance can increase ApoB: (38:08–39:25)
- How does ApoB predict heart disease risk?: (39:25–42:50)
- Why isn't ApoB included in typical lipid panels?: (42:50–44:25)
- Behavioral science and clinical practice: (44:25–50:06)
- How do GLP-1 agonists cause weight loss? (50:06–56:03)
- Negative side effects of GLP-1 medications: (56:03–57:36)
- Price of GLP-1s: (57:36–58:53)
- GLP-1: A short term quick fix or a lifetime prescription?: (58:53–1:02:19)
- Biggest health myths on social media: (1:02:19–1:08:45)
- Top tip for healthspan: (1:08:45–end)
About Dr. Spencer Nadolsky
Dr. Spencer Nadolsky (MD) is an obesity and lipid specialist physician with a passion for improving patient outcomes through innovative solutions. As the Medical Director for WeightWatchers, he is committed to developing cutting-edge programs that transform the way healthcare is delivered. With a background in telemedicine and fitness coaching, Spencer brings a unique perspective to the digital healthcare space.
What is a healthy metabolism?
Many people associate metabolism with calories burned in a day; however it encompasses a broader range of chemical processes within the body. Metabolism refers to the sum of reactions that occur in cells to provide the body with energy. The body utilizes calories from food to produce the energy needed to fuel bodily processes—including osteoblasts making bones, enzymes breaking down lipoprotein, and muscle cells contracting during physical activity.
So, what does it mean to have a healthy metabolism? Optimal metabolic health signifies the seamless functioning of all bodily processes, often evaluated through key blood biomarkers. Blood biomarkers, including HbA1c, fasting glucose, fasting insulin, ApoB, total cholesterol, triglycerides, and more, can help quantify metabolic function.
In contrast, an unhealthy metabolism can present as insulin resistance or type 2 diabetes.
Increased adiposity drives insulin resistance
The prevalence of insulin resistance and type 2 diabetes has experienced a significant surge within the US population in the past 20 years. [1] Dr. Nadolsky explains that one of the primary reasons for this surge is the excess energy in our diets. Energy surplus drives excess adiposity, which increases insulin resistance risk. “I believe we started seeing a lot more insulin resistance in the past few decades because of our adiposity,” he says. “And I don't think this is any fault of our own—it's our environment that causes us to over-consume food plus our genetics that combine together and result in obesity.”
What is weight health?
Individuals have varying capacities to gain weight—a concept Dr. Nadolsky describes as weight health. Weight health acknowledges that certain individuals possess a higher threshold for storing subcutaneous fat than others.
For instance, if an individual with a BMI of 35 is predominantly storing fat in areas like the legs, buttocks, and thighs, they could maintain good metabolic health regardless of weight status. In contrast, someone with a lower BMI might be carrying fat predominantly around the abdomen. Although this individual will appear healthier externally, they are experiencing compromised weight health, which can manifest as suboptimal blood biomarkers of metabolic health.
Is obesity a choice?
During this discussion with Dr. Nadolsky, he talks about his experience with having a large following on social media. As an obesity specialist physician, he enjoys debunking health myths and explaining scientific processes to his followers.
Dr. Nadolsky shares he often gets backlash for his take on the question: is obesity a choice? He notes, “People get really upset when you even insinuate that obesity is not a choice because people don't understand what that actually means.”
So what does “obesity isn't a choice” mean? Why is it so hard to develop healthy eating habits and break unhealthy ones? Dr. Nadolsky discusses three main reasons: genetic predispositions, childhood food choices, and our food environment.
Certain genetic variants increase obesity risk
Our genetics play a significant role in our predisposition to obesity. Emerging research has shown genetic variants can make people naturally inclined to prefer high-calorie foods rich in sugar, salt, and fat. Further, individuals who carry a variation of the fat-mass and obesity-associated (FTO) gene exhibit increased appetite, increased energy intake, and a preference for energy-dense foods [2,3]. These genetic factors can make it challenging for some individuals to lower their caloric intake, eat healthier foods, and maintain a healthy body weight.Childhood food choices impact food preferences later in life
In addition to genetic variations, childhood food choices and early exposure to various foods can have a life-long impact on eating habits. The food habits developed in infancy tend to continue into childhood and adolescence, influencing diet quality among adults. Research suggests that children who are not exposed to a diverse range of healthy foods in their early years may develop a preference for unhealthy options. This early conditioning can contribute to long-term unhealthy eating habits, increasing the risk of obesity and related metabolic dysfunction. [2, 4, 5]
How our environment influences obesity
If our genetics haven't changed since the 1900s, is the environment to blame for the rise in obesity? Dr. Nadolsky weighs in.
The increased availability of highly processed and palatable foods—often laden with added sugars, fat, and salt—makes it challenging to resist unhealthy options. Our biology, which once served us well in a feast-or-famine setting, now makes us vulnerable to an environment abundant in calorie-dense foods. “Even hundreds of years ago, humans would have slight variations in weight. Now, the environment exacerbates these changes in weight because we have an abundance of foods that are very easily over-eaten. When you combine genetic variations with these obesogenic foods, some people just eat a little bit more each meal, and over time, they develop obesity,” says Dr. Nadolsky.
What is GLP-1?
Glucagon-like peptide 1 (GLP-1) is a substance produced by the body from a gene called pre-proglucagon. GLP-1 is found in different parts of the body, including the pancreas, intestine, and certain areas of the brain. [6]
GLP-1 is important for controlling our appetite and maintaining a healthy weight. It works in two main ways:
- In the stomach and intestines, GLP-1 slows down the process of digesting food and how fast it moves through the gut, increasing satiety.
- Even if the stomach is empty or food hasn't been fully digested, injections of GLP-1 can enter specific brain areas and reduce the desire to eat.
The combined effects of GLP-1 in the gut and brain work together to help the body feel satiated with the amount of food consumed.
Scientists modified GLP-1 into a medication for diabetes treatment
The natural GLP-1 produced by our body has a very short lifespan and breaks down within minutes. This prompted extensive scientific research to enhance its effectiveness when administered through injections. Scientists succeeded in extending its half-life to approximately seven days.
Initially, GLP-1 agonists were explored as a treatment for type 2 diabetes. Researchers observed notable benefits, such as improved blood sugar control and weight loss in individuals. This marked a significant advancement compared to older diabetes medications, some of which caused weight gain and occasional hypoglycemia (dangerously low blood sugar levels).
GLP-1 agonists, in contrast, generally do not lead to excessively low blood sugar levels. Furthermore, they contribute to weight loss and serve as an alternative to insulin, representing a non-insulin approach to diabetes management.
GLP-1 agonists are changing obesity care
GLP-1 agonists are now going beyond diabetes care. These medications have undergone significant research and refinement, resulting in increasingly impressive outcomes for weight loss. Dr. Nadolsky points out that GLP-1 agonists now induce an average weight loss of 15 to 20% of total body weight with a once-per-week injection.
A key reason behind the success of GLP-1 agonists for weight loss lies in the presence of GLP-1 receptors in the brain, which profoundly influence our sense of satiety. Dr. Nadolsky explains that this isn't just about feeling full; it's about minimizing “food noise.” Individuals with obesity often experience fullness after a meal but still crave dessert—a phenomenon Dr. Nadolsky describes as food noise. This constant desire to eat, regardless of appetite level, is driven by our brain's reward center. Interestingly, GLP-1 agonists have a significant impact in this area, quieting the persistent urge for indulgence. These medications effectively help drown out the food noise.
Dr. Nadolsky shares his patient’s feelings, saying that nearly all of them have voiced the same sentiment—they still enjoy dessert and can indulge when they want to, but the once overpowering desire and relentless itch to give in to unhealthy cravings have greatly diminished. They often pose questions like, "Is this what it's like to feel normal? Is this the experience of living in a smaller body that doesn't require a daily battle to resist those tempting foods?"
Are there side effects associated with GLP-1 agonists?
Some people experience side effects when taking GLP-1 agonist medication. The most common side effect is mild nausea that typically resolves within a few weeks. In rare cases, people experience severe nausea and vomiting where they can not eat or drink. This becomes problematic because patients become dehydrated from not drinking, which harms kidney function.
What is the duration of prescription for GLP-1 agonists?
Dr. Nadolsky and his colleagues at WeightWatchers closely monitor a large patient population consisting of tens of thousands of individuals who are using GLP-1 agonists to address weight loss. In sharing some of his patients' diverse experiences, Dr. Nadolsky sheds light on how the duration of prescription may be highly variable from person to person.
Dr. Nadolsky has observed that while some individuals may require the highest dose of GLP-1 agonists for the rest of their lives, others can gradually reduce their medication. Some patients have successfully transitioned from a higher dose to the lowest dose while even extending the time between doses without regaining weight. However, there are instances where discontinuing the medication leads to weight regain.
Wherfe insurance coverage for GLP-1 agonists lacks, alternative medications can suffice for weight maintenance. Naltrexone—originally designed for depression, smoking cessation, and alcohol addiction—in combination with Bupropion has been successful in this instance. While these alternatives did not yield success in initial weight loss efforts, they have proven effective in maintaining weight loss. Initial weight loss can be achieved through less expensive and intensive medications.
While obesity is a chronic condition, this doesn't necessarily equate to lifelong medical therapy for all patients. Individuals with a genetic predisposition to obesity and lifelong appetite dysregulation may require ongoing medical intervention. Conversely, those who have recently gained weight due to life events like the pandemic, family matters, or lifestyle changes might benefit from temporary medication assistance to revert to healthier habits. This approach could help silence the "food noise" and create an environment conducive to maintaining weight loss. While these observations are anecdotal, they underline the need for more rigorous studies to shape the future of obesity management.
Top tip for healthspan
Dr. Nadolsky’s top tip for healthspan is to lift weights, ideally twice per week. For beginners, he recommends 10 minutes once per week,progressing to two or three times per week.
Similar Longevity By Design episodes we think you would love:
- How to Prevent and Reverse Insulin Resistance with Dr. Jennifer Lovejoy
- Insulin Resistance, Weight Management, and Eating Optimally with Dr. Mitch Roslin
- How to Use Behavioral Science to Build Healthy Habits with Dr. Kate Wolin
Resources:
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5407690/
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3726147/
[4] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1615722/
[5] https://pubmed.ncbi.nlm.nih.gov/12449287/
[6] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4119845/#:~:text=GLP%2D1%20enhances%20insulin%20secretion,promoted%20weight%20loss%20%5B52%5D.
