Semaglutide: a hot topic in health

What a wonderful day in the age where social media hype can drive inquiring minds to explore pharmaceutical drugs for weight loss.

I am not a “lose weight to be happy” advocate; instead, I like to educate about the importance of nutrition variety and moderation, stress-reducing, anti-diet approach to health and wellness.

Opportunities and questions are beginning to arise about a particular medication that doctors use off-label for weight loss, which is extremely expensive and hard to get. I will not be sharing names and companies here, as this is not bashing anyone or anything. Instead, this article will explore how nutrition may affect the body similarly to this popular medicine.

Originally, the FDA approved this popular injectable drug in 2017 to treat type 2 diabetes. However, since then, the side effect of weight loss drove the demand and usage up in the market, making it incredibly hard to get, let alone afford. Along with diet and exercise (the part on all commercials we tend to ignore), this blood sugar-helping medication is supposed to help lower blood sugar by a few different mechanisms:

1. delaying gastric emptying (red flag for side effects),
2. acting on glucagon-like peptide-1 receptors that communicate with the pancreas after a meal to secrete insulin and
3. signals to the brain to stop eating (Mahapatra et al., 2022).

However, the benefits also come with potential risks. Informed consent means knowing and understanding the risks before agreeing to medication, and it should be the best practice of all practitioners to share. Risk factors include increased risk of thyroid cancer, tumors, pancreatitis, pancreatic cancer, gallbladder, and kidney disease, as well as many other digestive discomforts, like nausea, vomiting, diarrhea or constipation, or heartburn (ASHP, 2023; Smits and Van Raalte, 2021).

Many digestive discomforts are due to delayed gastric emptying or slowing of the digestive process. While even some food influences the same receptors and slows the rate of digestion, our bodies need to be able to digest and move food through efficiently to reduce the risk of inflammation in the gut. Side effects of the medication are highly related to dose and concentration, and it doesn’t degrade and detox quickly, allowing it to linger (Sun et al., 2015; Mahapatra et al., 2022).

There is a food or herb for that!

The more we understand hormones and the mechanisms that control blood sugar regulation and appetite, the better we can investigate whether food or herbs offer similar benefits. That is one benefit this medication has provided to the nutrition community – how can we use food and herbs to work the same way? And this one is a no-brainer! Let’s dive in, shall we?

The GI system is one of my favorite systems to study. There is something beautiful about the ability to eat, digest, and absorb nutrients in a way that communicates with our body. Plus, trillions of tiny gut bugs are assisting us (hopefully) in creating even more nutrients from the nutrients we already ate! It’s just a fascinating, intricate design that lures me to need to know more. This topic is great because much of the conversation about how this medicine works starts in the gut!

GLP-1 is best known for its impact on insulin secretion as a response to eating carbohydrates, which is great in instances where insulin secretion is lessening. In addition to increasing insulin secretion, it also decreases the hormone that can increase sugar in the blood, known as glucagon. Some studies associate blood sugar dysregulation with a decline in GLP-1 (Bodnaruc et al., 2016). The goal with nutrition and herbal medicine would be use food to promote more GLP-1 secretion and interaction with the receptors – similar to the medication.

Foods and nutrients to increase GLP-1:

Prebiotic Fiber
Prebiotics fuel our microbiota. They are fibers that don’t digest and feed bacteria. When our gut bacteria ferment prebiotic fiber, they make a nutrient called short-chain fatty acids. One study demonstrated a diet rich in fermentable fiber for 50 days increased GLP-1 concentrations in the colon compared to the control diet(Mahapatra et al., 2022).

Resistant starch (a type of starch found in potatoes that also gets fermented by bacteria) can exhibit similar results. Prebiotic food and herbs include Jerusalem artichoke, chicory root, onions, leeks, garlic, oats, barley, green bananas, jicama, asparagus, dandelion root, burdock, and rye. Other foods high in resistant starch include plantains, green bananas, beans, lentils, and whole grains.

Essential fatty acids
There is a reason the Mediterranean diet is widespread, and olive oil is why (just kidding, there are other reasons). Mahapatra and colleagues (2022) describe unsaturated fatty acids as “potent stimulators of GLP-1 release,” citing multiple studies investigating the effects of olive oil on GLP-1 secretion. Numerous studies displayed better blood sugar regulation after 1-2 months with an olive oil-enriched diet. In addition to monounsaturated fats, omega-3 polyunsaturated fatty acids, such as fish oil and flax seed, reduce inflammation and increase GLP-1 with all of its glory mentioned above (Mahapatra et al., 2022).

Protein
You may have always heard health advice like “prioritize protein” or “eat your protein first,” and for a good reason. Protein is widely known to keep you feeling fuller longer, and now we know it is partly due to its influence on GLP-1. Protein comes in many different shapes and sizes. Plant-based may not have all the essential amino acids as animal-based does; therefore, working with a nutrition professional if you are vegan or vegetarian may be helpful to ensure nutrient requirements are met.

Other foods, herbs, and nutrients
We don’t just eat proteins, fats, and carbs; we eat whole foods that are beautiful combinations of macros, micros, and phytonutrients (chemical compounds in plants that have health benefits like antioxidants). Some other foods studied to help improve blood sugar, cardiovascular health, and metabolic syndrome includes eggs, avocado, pistachios, peanuts/peanut butter, raw almonds, and oatmeal (Mahapatra et al., 2022). Some herbals and phytonutrients with influence on GLP-1 include cinnamon, curcumin (turmeric), soybeans, resveratrol (grapes, peanuts, pistachios, blueberries, and cranberries), and tea (Camellia sinensis) (Yaribeygi et al., 2022).

Parting thoughts

Multiple factors influence blood sugar dysregulation, from genetics to nutrient deficiencies. Medicine is necessary where treatment is necessary; however, the beauty of nutrition and herbalism never ceases to amaze how they communicate balance and healing within the body. Researching foods and herbs that provide these benefits further demonstrates our healing potential.

Connect with Dr. Stephanie Lanham, DCN, CNS, LDN, NBC-HWC
RediscoverHealthLLC.com
@RediscoverHealthLLC\

Bodnaruc, A.M., Prud’homme, D., Blanchet, R. et al. (2016). Nutritional modulation of endogenous glucagon-like peptide-1 secretion: a review. Nutr Metab (Lond) (13, 92). Retrieved from: https://doi.org/10.1186/s12986-016-0153-3

Mahapatra, M. K., Karuppasamy, M., & Sahoo, B. M. (2022). Semaglutide, a glucagon like peptide-1 receptor agonist with cardiovascular benefits for management of type 2 diabetes. Reviews in endocrine & metabolic disorders, 23(3), 521–539. https://doi.org/10.1007/s11154-021-09699-1

Semaglutide Injection: MedlinePlus Drug Information. (n.d.). Retrieved June 6, 2023, from https://medlineplus.gov/druginfo/meds/a618008.html

Smits, M. M., & Van Raalte, D. H. (2021). Safety of Semaglutide. Frontiers in Endocrinology, 12. https://www.frontiersin.org/articles/10.3389/fendo.2021.645563

Sun, F., Chai, S., Yu, K., Quan, X., Yang, Z., Wu, S., Zhang, Y., Ji, L., Wang, J., & Shi, L. (2015). Gastrointestinal adverse events of glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a systematic review and network meta-analysis. Diabetes technology & therapeutics, 17(1), 35–42. https://doi.org/10.1089/dia.2014.0188

Yaribeygi, H., Jamialahmadi, T., Moallem, S.A., Sahebkar, A. (2021). Boosting GLP-1 by Natural Products. In: Sahebkar, A., Sathyapalan, T. (eds) Natural Products and Human Diseases. Advances in Experimental Medicine and Biology(), vol 1328. Springer, Cham. https://doi.org/10.1007/978-3-030-73234-9_36

What’s all the hype about injectables for weight loss?

You may have heard. There’s a new drug in town. And it’s magic.

Everyone wants it. Everybody’s talking about it. Your neighbor lost 27 pounds on it. Elon Musk is using it. And you could really use some help with this extra 30 pounds you have not been able to keep off since your last pregnancy. I hear you. And I have heard all the hype. All the media chatter.

My patients are asking for it, or about it; or they are fearful of it because they, too, have read the media hype. They have heard that once you discontinue it, the weight will come back. So, what’s the real story?

I am an obesity medicine specialist, a doctoral prepared nurse practitioner, a women’s health specialist and, the credential of which I am most proud: a member of the first cohort of nationally board-certified health and wellness coaches. I have been working in the field of obesity medicine since 2017.

History of obesity medicine

Obesity was first recognized as a disease in 1948 by the World Health Organization. The 1960s brought about important advances in the modern understanding of and available treatments for this disease but it was not until the last two decades that the distinct professional specialty of obesity medicine came about.

Still, many primary care physicians do not have training in the treatment of obesity as a disease and remain entrenched in old ways of thinking about weight loss. In fact, many of us have experienced a physician or other health care provider telling us to simply eat less and exercise more.

History of GLP-1 medications

It was not long after Victoza (liraglutide) was released in 2010 for the treatment of type II diabetes that physicians noticed that the weight reduction benefit reported in the clinical trials was relevant to their diabetic patients. It was not known at that time how GLP-1 medications worked to aid in weight loss, but it was theorized that the delay in stomach emptying helped to promote a sense of fullness. Soon, off-label use of Victoza in patients who were not diabetic but for whom weight reduction was recommended became common.

In 2014, there were two developments in the GLP-1 class of medications. Saxenda (liraglutide), a branded and FDA approved weight loss medication was released by NovoNordisk. Note that Saxenda is the same molecule as Victoza – liraglutide – however for marketing and insurance billing purposes it was rebranded under a new name. It was studied and approved at doses nearly twice that of the highest Victoza dose. The price tag was hefty; Novo Nordisk brought it to market with a savings coupon to build interest in the medication but even so, it was cost prohibitive for most consumers.

Gradually a few insurance companies came on board to provide coverage of Saxenda to their customers. Then, Trulicity, (dulaglutide) was released by Eli Lilly a competing pharmaceutical company. Trulicity was a unique molecule and it was intended for the treatment of type II diabetes.

In 2017, NovoNordisk brought a new medication to market after the extensive SUSTAIN clinical trials demonstrated efficacy for improvement in hemoglobin A1c, a marker of blood sugar control in diabetes. Ozempic appeared to deliver greater weight reduction than previous GLP-1 medications and was widely used off-label for weight loss by obesity medicine practitioners. In 2021, Novo released Ozempic’s sister drug: Wegovy which, at 2.4mg weekly, more than doubled the dose available in Ozempic, was FDA approved and marketed for weight loss. Nine months later a 2mg dose of Ozempic became available.

Recent medication shortages

The release of Wegovy in the spring of 2021 could not have been timed better if the goal was a complete frenzy of interest that would eventually fracture the manufacturers’ ability to keep up with demand: it hit the market during the peak of Covid pandemic lockdowns when most Americans were stressed, socially isolated and gaining weight. In the months preceding its rollout, there was a great deal of media attention for the upcoming new weight-loss version of Ozempic.

The coupon program that accompanied Wegovy’s release was generous, allowing patients to get a month’s supply of a medication with a base price of over $1000 a month for only $25 a month. The product flew off the shelves of pharmacies and soon Novo had to halt the coupon program due to inability to meet demand. By late summer and into fall, shortages were rampant, patients were frustrated, and obesity medicine practitioners knew that it would be easier to prescribe Ozempic than its popular new sister drug, for those patients who had coverage. So off-label use expanded once again.

By mid-winter that same year, Novo Nordisk’s manufacturing facility in Belgium that made the Wegovy pens had a snafu and had to halt production to redesign its manufacturing equipment. Practitioners were told to write no more Wegovy prescriptions until further notice. With much of the demand for semaglutide being met by Ozempic, it too fell into short supply at many pharmacies nationwide. Later that spring, in 2022, Novo Nordisk did release its 2mg Ozempic pens making Ozempic even more appealing as an off-label alternative, as the higher dosing did mean greater weight loss efficiency for patients.

The newest medication in this drug class came out in the summer of 2022. Mounjaro (tirzepatide) was developed by Eli Lilly and represented a unique approach to diabetes treatment. It combined the GLP-1 molecule with GIP (gastric inhibitory peptide), making it more effective for glucose control and for weight loss too. Eli Lilly appeared not to learn from Novo Nordisk’s experience with supply and demand issues. It came to market with a huge marketing campaign and a very appealing coupon. With supplies of Ozempic and Wegovy unpredictable, many practitioners took advantage of the coupon program to transition their patients to a medication they could actually get. Several months into its release, the coupon program was dramatically altered to make the medication coupon available only to those who had a diagnosis of Type II diabetes. Mounjaro is still being touted for weight loss. It’s sister drug, a weight loss version yet to be named, is scheduled to be released later this year but is still awaiting the FDA approval process.

Though the trio of medications waxed and waned in availability over the last several years, demand continued to grow as successful weight loss stories were shared over social media, backyard fences and the water cooler for those who had returned to the workplace. When patients with diabetes were met with the same supply issues as those using the medications for weight loss, the debate over appropriate use grew.

Off-label use of medications

Off-label prescribing of medications is not new and is not controversial. Prescribers learn that the FDA indicated use of a medication is not the only safe way to use that medication. Many commonly prescribed medications have multiple off-label uses. Antidepressant medications are commonly used in this way. Bupropion is an antidepressant that has FDA approval for smoking cessation at a very specific dose. Other doses are used for weight loss. Sertraline is another antidepressant that is used commonly offlabel. One of its uses is to treat nighttime eating syndrome.

At the height of media frenzy over the popularity and scarcity of these medications, off label use was criticized by those with opinions larger than their knowledge base. As an obesity medicine practitioner, I I stand firmly behind the off-label use of medicine. When I am treating a patient with a long-standing history of overweight and obesity, I do so with a solid understanding that I am helping them prevent the development of diabetes, heart disease, 14 different types of cancer, degenerative joint disease, liver disease, Alzheimer’s and dementia. I don’t care if they use the branded, FDA approved version of the drug or the one their insurance will cover.

Semaglutide and other compounded peptides

Compounding pharmacies did not take long to jump into the market to take advantage of demand for these medications. For the average consumer who wants the weight loss benefit of these medications, an out-of-pocket cost just 60% of the cost of the brand name medication and guaranteed availability, the appeal is real. They have no idea that the product they are injecting is not the real product, and has no FDA oversight, has met no standards for safe manufacturing and may contain additives with no proven weight loss benefit and possible harmful side effects. The Obesity Medicine Association released a position statement earlier this year stating that they do not support use of compounded semaglutide or tirzepatide and warning consumers against their use. The FDA echoed that warning in a statement on May 30th advising against the use of compounded weight loss and diabetes agents if FDA approved versions were available. The warning stated that the compounded versions were chemically different than the brand name medications and could have serious side effects. active. Those neuroendocrine changes persist even after weight loss comes to an end and the patient is simply trying to maintain the new, lower weight.

Consumers are not being given the whole story. Every day, I have patients ask me about compounded medications and will often point me to the website of a local med-spa or virtual physician practice that purports to be using FDA approved semaglutide combined with B-12. This is a blatant attempt to mislead the consumer into believing that they are taking an FDA approved medication. It is fraudulent and unethical and unsafe.

Ask yourself if you would give your child a version of acetaminophen (Tylenol) that your neighbor was manufacturing in the garage. Of course, you would not. That would be a foolhardy and dangerous thing.

Ozempic for Life?

I also get asked by patients nearly every day if they will have to be on Ozempic or Wegovy for the rest of their life. The answer is complex and based on the modern understanding that obesity is a complex disease of chronic metabolic dysregulation. It is a disease for which we have no cure. Statistics demonstrate the 85% of individuals who lose weight will regain it. When we treat chronic diseases like high blood pressure, we help our patients understand that they may require that medication for the rest of their life. Indeed, if the patient recently started on a blood pressure medication undertakes serious and life altering behavior change such as quitting smoking, taking up daily exercise, changing to a Mediterranean diet, and learning to manage stress with breathing exercises or meditation and if all those changes were maintained, they might no longer require medication to lower their blood pressure – but they would have to continue all the lifestyle changes. If the lifestyle change is not permanent, the medication will be. And sometimes, the medication will be required in spite of the lifestyle change. t pressure medication undertakes serious and life altering behavior change such as quitting smoking, taking up daily exercise, changing to a Mediterranean diet, and learning to manage stress with breathing exercises or meditation and if all those changes were maintained, they might no longer require medication to lower their blood pressure – but they would have to continue all the lifestyle changes. If the lifestyle change is not permanent, the medication will be. And sometimes, the medication will be required in spite of the lifestyle change.

In the same way, if someone has struggled with their weight for decades and is finally able to lose weight with a safe and effective medication but does not undertake drastic and lasting lifestyle change, they should plan to continue the medication long-term. Many will continue to benefit from the medication even if they do make dramatic changes to improve their nutrition, exercise, stress management and sleep while losing weight. As an obesity medicine practitioner, I help my patients understand the neuroendocrine role that the fat cells play in the body, taking on the same influence that an organ might have in the body: secreting cytokines and signaling agents that increase appetite, decrease satiety and decrease the desire to move and be.

Weight bias in healthcare, science and society

As a culture we have learned to confront our biases in many areas. However, overweight and obesity remain health issues for which individuals are often harshly judged. Unlike other health concerns, weight loss is something for which nearly everyone feels some degree of personal experience and expertise. They either lost weight or never had to and they attribute their success at getting or staying ‘thin’ to eating and or exercising a specific way.

Without any concept of the genetic, environmental and physiologic drivers of weight gain, many of us would like to take personal credit for being a healthy weight. The unfortunate flip side of that line of thinking is that people with obesity must be personally responsible for their weight. If weight is an issue of character or self-discipline, then perhaps we ought to be able to lose weight “on our own”, perhaps those who use medications are “cheating” or using a “crutch”. This way of thinking about weight is endemic in diet culture but we all must work hard to eradicate it.

People who struggle with the chronic metabolic disease of overweight or obesity deserve the same compassionate, empathetic response we give to anyone with a chronic disease. They deserve evidence-based ools to help them push back against the physiologic drivers of weight gain. Medications like Ozempic and Wegovy are dramatically different than older, oral medications. Many claim they are “game-changing”.

But they do not work in isolation. To best support our patients to achieve lasting improvement in their metabolic health, these medications should be combined with comprehensive support for lifestyle change. Working to create a healthy relationship with food, structuring our environment to enhance sleep and improve stress management, gradually improving our activity and exercise routines – these are challenging tasks. Patients will need support to make the changes and embed healthy new habits.

As a nurse-practitioner, I am responsible for safe prescribing; and I am happy to be able to put these effective and safe medications into the hands of my patients.

As their health coach, I know that medication is not magic, and that the prescription is just one tool in their toolkit.

Connect with Dr. Rachel Smith, DNP, NP-C, CNM, APRN, NBC-HWC
Rachel5303@gmail.com
309.292.0313