Ozempic
Ozempic is all the rage right now.
Is it the magic weight loss answer we have all been hoping for?
Background:
Over 40% of U.S. adults are obese. Step back in time sixty years - 13% of U.S. adults were obese. More and more children are also obese.
In the last decade alone, the U.S. has invested almost $11 billion in the attempt to understand this pattern. Yet there's no evidence to suggest that we have made any progress. Some argue that it’s the medical failure of our time.
No wonder there has been so much interest in meds like Ozempic.
Furthermore, the #1 complaint of my postmenopausal patients is unexplained weight gain. Meaning – “I’m eating the same and exercising, yet the scale number just keeps climbing”.
I’d love nothing more than to present all my postmenopausal patients with a gift, wrapped in a beautiful red ribbon, containing THE answer to this frustrating situation.
What it is:
Two drugs, which are FDA-approved to treat type 2 diabetes, have become well known for their weight loss properties. Ozempic is made by Danish drugmaker Novo Nordisk, and Mounjaro is made by Indiana-based Eli Lilly and Co.
It's part of a growing group of drugs called GLP-1 (glucagon-like peptide 1) receptor agonists. This means it stimulates GLP-1 receptors via a peptide called semaglutide as its main ingredient. Semaglutide is a synthetic version of GLP-1, which is a hormone produced in the gut and released in response to food.
It causes reduced appetite and the release of insulin from the pancreas. Additionally, GLP-1 reduces gastric emptying and intestinal glucose uptake, suppresses glucose production from the liver, and promotes satiety.
The FDA approved Ozempic's cousin, Wegovy, for "weight management" for obese patients a few years ago, whereas Ozempic is currently only approved for diabetes treatment.
Patients who don't fit the criteria can get off-label prescriptions if they can afford to pay out of pocket, often $300- $1,400 a month.
Here is a typical dosing (all done via injection):
Week 1-4 0.25 mg/week
Week 5-8 0.50 mg/week
Week 9-12 1.00 mg/week
Week 13-16 1.7 mg/week
Ongoing dose 2.4 mg/week
Weekly doses higher than 2.4 mg are not recommended.
How it works:
Researchers aren't entirely sure how this class of drugs, GLP-1 agonists, work for weight loss. Diabetes was the original target, and weight loss effects were a surprise. "That right there should be a clear sign of how little we understand about obesity." says Dariush Mozaffarian, MD, a cardiologist and nutrition professor at Boston's Tufts School of Medicine.
Certainly, appetite suppression and insulin production are at least partial explanations.
Arguably, we don’t naturally produce semaglutide in our bodies. However, our bodies should produce GLP-1.
So why might we not be making appropriate levels of this hormone, GLP-1?
Genetics, certain medical conditions, poor diet and lifestyle, and certain medications can all affect this hormone.
Hard to say if it’s the chicken or the egg, but lower levels of GLP-1 are connected to poor blood sugar control, overeating, weight gain, sedentary lifestyles, slowed gastric emptying, and insulin resistance.
Are there other ways to stimulate GLP-1 production?
Food is the main stimulus of GLP-1 (I suspect overeating and eating too frequently can decrease GLP-1)
Nerve activity and other hormones can also affect GLP-1 release (I suspect stress, eating on the run, eating too quickly, not breathing deeply are all causes here)
Meals with higher protein stimulate GLP-1
Dietary fiber also increases GLP-1 levels (Only 5% of men and 9% of women are getting the recommended daily amount of dietary fiber. The goal is 25 grams/day for females and 38 grams/day for males. Note: Our hunter-gatherer ancestors are thought to have eaten about 100-150 grams/day!)
The following polyphenols are reported to increase GLP-1 levels:
Apigenin – found in many plants including parsley, spinach, chamomile, thyme, oregano and basil
Curcumin – naturally occurring in turmeric
Delphinidin 3-rutinoside – highest in blackcurrents (Ribes nigrum)
EGCG – a component of green tea
Genistein – concentrated in soy
Hispidulin – large amounts found in sage, and Artemisia (aka wormwood)
Isoquercitrin – a highly active form of quercetin found in pistachio nuts, fresh black chokeberries, onions, amaranth, and Chinese hawthorne fruit
Luteolin – found in carrots, peppers, thyme, broccoli, onion leaves, cabbages, apple skins, rosemary, parsley, and spinach
Myricetin – concentrated in tomatoes, oranges, nuts, berries, red grapes, and tea
Proanthocyanidin Gallic acid - in blueberry, blackberry, strawberry, plums, grapes, mango, cashew nut, hazelnut, walnut, and tea
Procyanidin – in fruits, beans, and nuts
Resveratrol – in grapes, peanuts, cocoa, blueberries, bilberries, and cranberries
Obesity theories:
For the sake of argument, let’s say that lack of semaglutide is the bloodstream is NOT the cause of weight gain.
Then what is the cause?
Like every health issue, it is likely the culmination of several aspects.
The quality of our food (namely, sugars and processed carbs) may have changed our bodies' response to food when compared to decades past.
Animal studies show changes in gut microbes may impact metabolism and body weight. Some research suggests that fecal transplants or even post-biotics may improve the metabolic health of subjects with obesity.
Another possibility is the impact of diet on our epigenetics, or the way our genes are expressed. Epigenetics allows some genes to turn on and off though various mechanisms like exposure to nutrients, chemicals, and hormones.
Technology, including cars, cellphones, Netflix, and computers keep us sitting in one place for many hours each day.
Our food often doesn’t perish. We never have to go without.
Brain activity controls food intake and responses to a changing food environment in ways that are still being elucidated, resulting in overeating and obesity. Some studies suggest obesity may permanently impair the brain’s response to satiety.
Highly processed carbohydrates trigger hormonal responses that may lead to excess fat storage.
Obesogens – chemicals found in our air, plastics, clothing, pesticides and herbicides lead to weight gain by altering hormones and metabolism.
Additionally, weight gain is a side effect of many medications, including antidepressants, insulin, antipsychotic meds like lithium, steroids, birth control pills, and blood pressure meds.
Benefits of GLP-1 receptor agonists like Ozempic, Wegovy/semaglutide:
Blood glucose decrease
Weight loss
Novo Nordisk claims its obesity drug semaglutide (Wegovy) cut the risk of major cardiovascular events by 20% in patients overweight or obese with a history of heart disease.
Side Effects & Risks
First off, please remember that side effects should be renamed “effects”.
A 2022 study found that most people regain the weight and cardiovascular risks they lost within a year of stopping Ozempic.
A known increased risk for diabetic retinopathy complications in patients with a history of diabetic retinopathy at baseline exists. Note: some claim this is transient/not permanent.
Hair loss appears to be more prevalent with this med (note: this may be associated with weight loss and or nutrient depletion)
A current lawsuit claims that companies failed to disclose the drugs' risk of causing severe vomiting and diarrhea due to inflammation of the stomach lining, as well as the risk of stomach paralysis (called gastroparesis).
The prescribing labels for Mounjaro and Ozempic state that each “delays gastric emptying" and warn of the risk of severe gastrointestinal adverse reactions. The prescribing labels for both drugs state that the most common side effects include vomiting, diarrhea, and stomach pain.
The Ozempic label does not mention gastroparesis, and the Mounjaro label states that the drug has not been studied in people with the condition and is therefore not recommended for people who have it.
Nausea is quite common
There may be the possibility of long-lasting effects on thyroid and reproductive health, especially for women that we still don't know enough about.
Of more than 1200 reports of adverse reactions with semaglutide, 60 cases of suicidal ideation and seven suicide attempts have been reported since 2018,
GLP-1 agonists have been associated with asymptomatic pancreatitis and pancreatic cancer in limited studies, but this association is still being studied.
There is a theoretic concern about the risk of pancreatic burnout of the beta cells, which could result in a condition similar to type 1 diabetes.
Given that insulin secretion is pulsatile in nature, it seems unlikely that chronic continuous stimulation of insulin secretion could be beneficial for long-term beta cell function.
Beta cell rest, as is accomplished in a natural setting between meals, is necessary. GLP-1 receptor agonists block beta cell rest and ask for continued insulin secretion.
With prolonged use, several long acting GLP-1 receptor agonists were not able to continue their mechanisms, and therefore glucose and weight gain increased over time. This is a medical term called “tachyphylaxis”, a rapidly diminishing response to successive doses of a drug, rendering it less effective. In other words, continued drug doses are eventually ignored by the body’s cells. Some studies even show that blood glucose levels can eventually worsen from baseline with continued GLP-1 receptor agonist use.
When to consider using these meds:
If overweight with a body mass index (BMI) greater than 27 (not appropriate criteria in those with dense muscle mass)
Additional medical issues like type 2 diabetes, high blood pressure, and or high cholesterol
Absolute reasons to not use these meds:
Hypersensivity reactions
Family history of C-cell tumors
Multiple endocrine neoplasia (MEN)
Type 1 diabetes
Pregnancy and preconception – (discontinue at least 2 months prior to becoming pregnant)
Avoid with a history of suicide attempts or active suicidal ideation
Avoid use it those with gastroparesis or delayed stomach emptying
Caution:
If gallbladder issues / stones
If renal impairment or end-stage renal disease (renal failure)
If experiencing depression
During lactation
If greater than 65 years of age – more risk for low blood sugar
In use with alcohol
Decrease doses of sulfonylurea or insulin if using at the same time
Yay or Nay?
I would advise that this med should not be used for cosmetic reasons.
If you want to use it and are a good candidate, you need to be OK with the idea of staying on it longterm to sustain weight loss but also realize there could be downsides to using longterm (see side effects and risks section).
If you are overweight (BMI of 25 and 29.9) and do not have other cardiometabolic risks, I would advise against it as the risks likely outweigh the benefit of weight loss.
You can calculate your BMI here.
Underweight = <18.5
Normal weight = 18.5–24.9
Overweight = 25–29.9
Obesity = BMI of 30 or greater
Final thoughts:
Sometimes, people just need a win. It is possible that a chunk of weight loss can inspire many of us to make bigger changes.
However, do keep in mind the drug would need to be taken for a lifetime (with other possible negative effects) to keep the weight off, unless root causes were addressed along the way.
This drug is certainly not addressing weight gain from a root cause. When the drug is stopped, the weight comes back.
This editorial article says it well: “History has taught us that enthusiasm for new classes of drugs, heavily promoted by the pharmaceutical companies that market them, can obscure the caution that should be exercised when the long-term consequences are unknown.”
This article goes on to say “We feel that enough preliminary evidence has accumulated to suggest that there is a plausible risk that long-term recipients of GLP-1–based therapy may develop asymptomatic chronic pancreatitis and worse, subsequently a minority of individuals treated by this class of drugs may develop pancreatic cancer.”- Butler PC, Dry S, Elashoff R. GLP-1-based therapy for diabetes: what you do not know can hurt you. Diabetes Care. 2010;33(2):453-455. doi:10.2337/dc09-1902
That alone, is enough for me to use this as a last resort for my patients.
The Good News:
Naturopathic medicine has many other tools to use in place of meds like this:
o Intermittent fasting
o Whole foods
o Dense fiber intake
o Polyphenols like resveratrol and curcumin
o Berberine
o Resistance exercise
o Vitamin D
o Gut microbiome shifts – i.e. via pre, pro, post biotics, fiber and short chain fatty acid
o Also refer back to the “Are there other ways to stimulate GLP-1 production?” section
In my opinion, drastically lower fiber intake (when compared to decades past), obesogens (aka glyphoshate/Round-Up), low sex hormones, and altered gut microbes are the main causes of unexplained weight gain.
So no, these meds are not the answer to weight gain that we have all been hoping for.
I know this may not have been the answer you were looking for.
But remember that pharmaceutical companies have a vested in you believing these meds are the secret.
Yes, weight loss can occur, but not without many risks along the weigh. <—— I couldn’t help myself.
💕
Dr. Laura Neville
References:
Butler PC, Dry S, Elashoff R. GLP-1-based therapy for diabetes: what you do not know can hurt you. Diabetes Care. 2010;33(2):453-455. doi:10.2337/dc09-1902
Hira T, Trakooncharoenvit A, Taguchi H, Hara H. Improvement of Glucose Tolerance by Food Factors Having Glucagon-Like Peptide-1 Releasing Activity. International Journal of Molecular Sciences. 2021; 22(12):6623.
Morgan & Morgan: “United States District Court, Western District of Louisiana, Lake Charles Division, Case 2:23-cv-01020, Jaclyn Bjorklund, Plaintiff, v. Novo Nordisk et al."
Van Raalte, D. H., & Verchere, C. B. (2016). Glucagon-Like Peptide-1 Receptor Agonists: Beta-Cell Protection or Exhaustion? Trends in Endocrinology & Metabolism, 27(7), 442–445. doi:10.1016/j.tem.2016.04.009
Wilding JPH, Batterham RL, Davies M, et al. Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension. Diabetes Obes Metab. 2022;24(8):1553-1564. doi:10.1111/dom.14725