Why is Ozempic Taking Over Hollywood?

Pharmaceutical breakthroughs come and go, but certain drugs leave a lasting mark on society. Oral contraceptives sparked the sexual revolution in the 1960s. Mental health came into the spotlight in the 1980s thanks to Prozac (fluoxetine). Blockbuster drugs arise infrequently but with transformative power when they do.

Today, we step into the latest blockbuster class of medications: glucagon-like peptide 1 receptor agonists (GLP1RAs). Brand names such as Ozempic, Wegovy, and Mounjaro have made their case to be household names. Initially developed to address diabetes, their rise in popularity is due to their astounding weight loss potential.

The impact of these drugs is not limited to the medical world. They have become a part of our daily conversations, with news, social media, and TV frequently referencing them. The experiences of notable celebrities like Sharon Osbourne, Mark Wahlberg, and Elon Musk have further fuelled the discussion¹. However, the popularity of these drugs has led to a global shortage, with the European Medicines Agency (EMA) predicting that the scarcity of Ozempic will persist until 2024, highlighting the urgent need for these medications² ³.

The Economics

The public health importance of GLP1RAs is evident, but their financial performance adds an impressive extra layer. Projections estimate that combined sales of Novo Nordisk’s Ozempic, Wegovy & Eli Lilly’s Mounjaro are expected to soar to an astonishing $53 billion by 2028⁴.

Novo Nordisk and Eli Lilly have added an astonishing $339 billion in market capitalisation this year. Novo Nordisk derives 52% of its $23.6 billion in revenue from Ozempic & Wegovy alone⁵. However, as these pharmaceutical giants soar, other sectors have felt the pinch, exemplified by a 12% decline in the S&P Food & Beverage Select Industry Index over the past three months. Iconic brands such as Kraft Heinz, Hershey, Coca-Cola, and PepsiCo have seen their shares decline significantly, suggesting a profound impact of these pharmaceutical advancements. These far-reaching financial implications underscore the pivotal role of GLP1RAs in reshaping the healthcare and economic landscapes⁶.

Glucose Regulation & Diabetes

To understand how GLP1RAs like Ozempic work, we must introduce how our body handles sugar (glucose). When we eat, our digestive system turns food into nutrients, including glucose, which enters our bloodstream. Our body uses two hormones, insulin and glucagon, to control blood glucose levels. Insulin helps store excess glucose after meals, while glucagon signals the release of stored glucose between meals and at night. Maintaining this balance requires a healthy diet, adequate physical activity, and stress management.

Factors like overeating, lack of exercise, and overindulging in processed foods can lead to type 2 diabetes mellitus (T2DM), which can affect both lifespan and quality of life. T2DM is a disease that results from persistently high blood sugar, leading to fat storage, a shortage of insulin, and an inadequate response to insulin. T2DM can cause severe cardiovascular disease, kidney problems, nerve damage, memory decline, and many other health issues that ultimately shorten health span and lifespan⁷.

GLP-1 Analogues: What are they & How do they work?

GLP1RAs are medications designed to imitate the actions of glucagon-like peptide 1 (GLP-1), a hormone produced naturally. GLP1RAs do this by stimulating and activating the same receptor that natural GLP-1 acts at. Think of GLP-1 and GLP1RAs as keys that work on the same lock.

GLP-1 is primarily produced in the small intestine, but there is also a naturally occurring brain-derived version, GLP-1, functioning more like a neurotransmitter⁸. This dual role of GLP-1, both as a hormone and neurotransmitter, is increasingly recognised and evident in the effects of GLP1RAs.

GLP-1 regulates blood sugar levels by stimulating insulin release, inhibiting glucagon (further facilitating cell uptake), slowing stomach emptying, and reducing appetite. These effects occur by binding to specific receptors in various organs, including the pancreas, nervous system, gastrointestinal tract, cardiovascular system, kidneys, and lungs. Due to GLP-1’s natural influence on multiple body systems, this new class of drugs holds potential for both intended and unintended effects.

What are the Benefits of Ozempic?

Compared to existing diabetes medications, GLP1RAs offer substantial improvements. They lead to significant reductions in diabetes markers like HbA1c (a measure of average blood glucose over 120 days). Clinical trials unequivocally show their superiority at improving glycemic control, reducing weight and blood pressure, and providing cardioprotective benefits—all without the risk of hypoglycemia⁹. As a result, GLP1RAs have revolutionised diabetes management guidelines¹⁰.

As for weight loss evidence, the early GLP1RAs didn’t initially offer significant weight loss benefits. However, semaglutide (Ozempic) changed the game by causing a remarkable 15 – 16% weight loss in research studies. Since then, it’s not unusual for GLP1RAs to consistently lead to weight loss of up to 15 – 20% in people dealing with obesity¹¹ ¹² ¹³. As a result, many medical guidelines have been updated to include obesity as a reason to use GLP-1As, even though they were created to treat diabetes¹⁴.

These findings have garnered significant attention, seemingly highlighting a new panacea with headline reports, such as the New York Times proclaiming, “Ozempic reduces the risk of heart attack, stroke, or cardiovascular-related death by 20%”¹⁵.

But the list is almost endless: studies indicate potential cardioprotective effects, including lessening the changes in the heart’s structure during heart problems like heart attacks and chronic heart failure, reservation of kidney function through a pro-diuretic effect by activating the kidneys, and even benefits for patients with asthma ¹⁶ ¹⁷ ¹⁸.

There’s also potentially neuroprotective properties involving glial cells, a type of cell found in the brain, reducing oxidative stress and suppressing food intake and even potentially improving symptoms in patients with Alzheimer’s & Parkinson’s disease¹⁹ ²⁰.

However, it’s essential to note that each country’s clinical trial outcomes and drug regulatory processes strictly define the use and prescription of GLPR1As. Using these drugs for reasons other than those approved by regulatory authorities constitutes off-label prescribing, placing liability on the prescribing doctor, often with dire consequences after the fact.

The dramatisation of the Insys Therapeutics scandal on Netflix, “Pain Hustlers”, reveals the dark side of off-label prescribing (alongside plenty of other nefarious tactics in that specific case). Off-label prescribing often occurs as regulations catch up with evolving use cases but carries its own set of risks.

What are the Side Effects, Risks and Unknowns with Ozempic?

Like all medications, GLP-1As have potential side effects, and unfortunately, the high demand for these drugs has led to counterfeit versions flooding the market²¹. Common side effects include nausea, vomiting, and injection site reactions²². Genetic factors can lead to non-responsiveness. Hence, genetic testing may personalise treatments for type 2 diabetes and obesity, enhancing their effectiveness and safety²³.

Some studies hint at possible links to pancreatitis or thyroid cancers, but more long-term research is needed to quantify this risk²⁴. If considering GLP-1As for weight loss, be aware that most patients regain weight after stopping treatment, leading many to believe these drugs are lifelong treatments unless permanent behavioural changes are also achieved²⁵ ²⁶. Concerns about potential muscle loss have also been raised²⁷. Time will undoubtedly be the ultimate test for this new class of medications.

Long-term cohort and retrospective studies are crucial and already underway. Novo Nordisk sponsors an ongoing study involving 17,000 adults aged 45 and older to assess the weight loss and cardiovascular benefits even after discontinuing the medication²⁸. However, because these drugs are relatively new, there’s still much to learn about their long-term effects.

TLDR;

In this latest era of pharmaceutical innovation, GLP1RAs have emerged as transformative agents. Initially developed to combat diabetes, these medications have transcended their original purpose and offer a new frontier in obesity management. The profound impact of GLP1RAs is evident in their benefit to patients, the staggering financial projections, and their ability to reshape healthcare and economic landscapes across society.

These drugs regulate blood sugar, foster weight loss, lower blood pressure, and even exhibit cardioprotective properties, all without the dangers of hypoglycemia. We have highlighted some of the concerns and potential side effects of these drugs, all while raising questions about long-term benefits and risks.

Looking ahead, the horizon holds promise and uncertainty in equal measure. Long-term studies are ongoing, aiming to uncover the enduring benefits and potential drawbacks of GLP-1 analogues. These medications are in their infancy, and time will ultimately judge their place in the pharmaceutical landscape. In the meantime, seek advice from your primary care physician if you think GLP-1A medication is for you and continue prioritising habitual lifestyle changes for lasting health benefits.

References

[NB. All images created using MidJourney]

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