By Gary M. Pepper, M.D. Ozempic, Rybelsus, Trulicity, Wegovy, Saxenda are the central players in the weight loss craze sweeping across the globe. Metabolisim.com has been monitoring this phenomenon from its beginnings in 2008 with its report “Lizard Spit Reduces Blood Sugar and Appetite”, regarding the first drug in this class, Byetta (exenatide). Caught In the middle of the current chaos are the medical experts who treat diabetes and have been prescribing these medications for more than a decade. Here is a brief commentary from one such board certified endocrinologist; “I started treating Type 2 diabetics with GLP-1 agonists more than 10 years ago. In some respects, these medications have revolutionized the treatment of diabetes by lowering blood sugar effectively and promoting weight loss at the same time, a unique combination of benefits. Not everyone benefits from these drugs to the same degree unfortunately, and I have seen lots of patients experience unacceptable side effects from them. Nothing though, has prepared me for what is happening now. Too often, I find myself confronting someone who expects me to prescribe one of these drugs just so they can lose weight. Sadly, one extreme example was someone who, despite battling a life threatening medical condition, was insistent on getting a prescription. At the same time my diabetic patients are scrambling to find a place to buy their medications if they can even afford it. It is disheartening, to say the least, and I dread the negative interactions with some of my patients I now face almost daily.”
Off- Label Use
The FDA is the U.S. government’s department tasked with evaluating and approving drugs for specific medical conditions. When a new medication is approved for treating a medical condition by the FDA the agency will, at the same time, set strict guidelines for exactly which patients may use the newly approved drug. When a medication is used “off-label” it means that these limitations are being overridden by the provider for a potential benefit which outweighs the drugs risks. It is a general misconception that off-label means illegal; it does not. This practice has been going on for ages and more than 20% of prescriptions in the United States are prescribed off-label. A common example is the use of beta-blockers (approved for heart problems) for the treatment of performance anxiety.
GLP-1 agonist drugs, as discussed recently by metabolism.com. were originally approved for the treatment of Type 2 diabetes in adults. In the past few years most of these same medications have gained unprecedented popularity for their “off-label” weight loss benefit. Of the 5 GLP-1 agents presently in U.S. pharmacies only Wegovy (semaglutide) and Saxenda (liraglutide) are FDA approved for treating obesity. Of these two, Wegovy is the newer and had been much more popular that its sister drug Saxenda, probably due to being dosed only once weekly compared to daily for Saxenda and less likely to cause side effects. Due to Wegovy’s soaring popularity, its manufacturer, Novo Nordisk, increased the price of Wegovy two times since its initial release. The CEO of Novo Nordisk stated that Wegovy prescriptions hit a peak within weeks of its appearance in pharmacies while in comparison it took Saxenda 4 years to reach the same level. By the end of 2022, the FDA listed both drugs in shortage and for several months at the end of 2022, Wegovy was actually unavailable. The result has been an equally unprecedented surge in off-label prescriptions of GLP-1 drugs such as Ozempic (semaglutide) approved for Type 2 diabetes treatment being used instead for weight loss.
The spike in demand for this whole class of drugs has created a mad scramble, exposing some key issues in the national healthcare system concerning supply, cost, and inequities.
While the healthcare system has looked on in bewilderment and pharmaceutical industry profits have surged, the nation’s diabetics are often finding it impossible to find a pharmacy that has these medications in stock, and when they do, many are unable to afford them. Healthcare providers acknowledge that the shortage of GLP-1 agents is having a significant negative impact on their ability to care for those with diabetes. Worse still, is the recognition that these medications intended to save lives are now replacing the simple lifestyle modifications which for decades were upheld as the central principles for sustainable obesity treatments.
Professor Li from the University of California when discussing these matters, states ‘I don’t wish for people to lose the attention on the main issue- we need to help each individual acquire the best lifestyle for their bodies and themselves.’
Could we be undergoing another wave of vanity insanity? Let’s dig in further to find out.
Ozempic is a semaglutide sister to the weight loss drug Wegovy and works in a similar way to reduce weight by making patients feel fuller. This drug was approved in 2017 by FDA for the treatment of Type 2 diabetes in adults only. Novo Nordisk has listed a shortfall of Ozempic since August 2022. Novo says, ‘the short supply is a global concern, and is due to a high demand’.
The hashtag #Ozempic has gained massive popularity on TikTok having more than 273 million views. Ozempic is also the talk of Hollywood. Patti Stanger the producer of ‘Millionaire matchmaker’ nick named Ozempic the ‘Hollywood drug’.
When asked about the off-label use of their medication, Novo acknowledged the existence of this widespread practice but placed its trust in the practitioners’ discretion for prescribing Ozempic. Novo has clearly stated it ‘does not promote, suggest or encourage off-label use of medicines.’
Many insurance companies are now refusing to cover weight loss drugs, and Wegovy priced at $1336 per month at the time of this writing, is quite a bit more expensive than Ozempic which is $914 per month. People not meeting the appropriate FDA criteria and purchasing these drugs for cash might be influenced by the difference in price. With these consumer issues in play, Ozempic sales have gone up to 63% (2.3 billion dollars) in just the last 3 months of 2022 while Saxenda reached 54% (142 million dollars), despite Saxenda being the approved drug for weight loss.
Not enough evidence exists to support the use of Ozempic for weight loss in a non-diabetic population. The Wall Street Journal writes that Ozempic use has not been studied thoroughly in healthy patients, and both Ozempic and Wegovy are not recommended for casual weight loss.
Trulicity (dulaglutide), another FDA-approved drug for diabetes, is also trending as a popular weight loss treatment. Studies show that Trulicity causes significant weight loss, and in the AWARD-11 trial, higher doses of Trulicity resulted in extreme weight loss in patients with the highest body mass index (BMI). It is important to note that all patients had Type 2 diabetes and Trulicity effectiveness in non-diabetic patients is yet to be tested.
Trulicity is produced and marketed by Eli Lilly and by 2019 was already one of the company’s most profitable drugs ranking as the 19th most revenue-grossing drug globally at that time, with revenue soaring to over $7.4 billion dollars in 2022.
Despite its off-label use Lilly only highlights Trulicity for weight loss as a secondary benefit and doesn’t market it to be suitable for obesity treatment.
In December 2022, the FDA acknowledged Trulicity’s shortage, and the company is also working towards enhancing the manufacturing capacity in North Carolina, aiming to double its production by the end of 2023.
Insurance doesn’t cover Trulicity for weight loss but through an employer or private insurance, 92% of the patients can get Trulicity for under $30 if they meet the requirements, while patients with Medicaid can get it for $4-$9 per month. Alternatives for Trulicity are limited and without insurance, it costs approximately $809 per month.
Mounjaro (tirzapatide) is a unique drug with dual action activating both GLP-1 and GIP receptors. Although only approved for treatment of Type 2 diabetes, Mounjaro has been the star of off-label prescriptions for weight loss. Mounjaro causes weight loss and signals the brain to enhance satiety (feeling full) and slows the movement of food through the gut.
In October 2022 , Mounjaro got fast-track designation for weight loss management by the FDA, thus encouraging many physicians to start prescribing Mounjaro early on. However, till now only the first of the required trials, SURMOUNT-1 , is completed. While further testing is on-going, Lilly plans to have a submission for the weight loss indication rolling by April 2023, even before completing all required trials.
The President of Lilly stated that ‘most patients don’t achieve their desired treatment goals with only diet and exercise. We are dedicated to helping people living with obesity through our research and development of innovative treatments like tirzepatide (Mounjaro)’.
Mounjaro also entered the FDA shortage list in December 2022, owing to the high off-label use. In view of the GLP-1 craze, Eli Lilly tweaked its discount coupons in October 2022 allowing people diagnosed with Type 2 diabetes to get Mounjaro for as low as $25 in comparison to $999 per month for uninsured purchases. Lilly also addressed the shortage and plans to double the supply by the end of 2023. Analysts speculate that Mounjaro could surpass all obesity drugs, hitting a record $25 billion in annual sales. The competitor Novo has also elevated its obesity drug sales target to $3.7 billion.
Despite its growing popularity, Moujaro’s safety for weight loss is still under review with warnings of serious side effects like pancreatitis, low blood sugar, kidney failure, vision problems and severe allergic reactions.
Are these Weight Loss Drugs Even Safe?
Without question, these miracle weight loss drugs are immensely popular, but the hype created by social media often masks the negative side effects associated with GLP-1 drugs.
Semaglutide (Ozempic, Rybelsus & Wegovy) is not only incredibly expensive but can also generate a significant health cost, while providing only a temporary fix. Studies show that Wegovy is safe for 68 weeks of use, but long-term use is yet to be explored, and a study published in Diabetes, Obesity, and Metabolism in April 2022 found that patients gain all the weight back once stopping the wonder drug. Although manufacturing companies offer temporary discounts, not everyone can spend thousands of dollars every month, as many insurance companies are tightening their restrictions and denying coverage for non-diabetic use.
Individually a single drug can cost you a month’s rent (see figure 1), so is it even feasible long term?
Figure 1: Per month Price (in dollars) of GLP-1 drugs as of February 2022 on Goodrx.com
Many doctors argue that obesity is a chronic condition and needs chronic treatment. Dr Singh, a renowned endocrinologist states that only 25% of his patients who have used these medications for weight loss have been able to sustain the lower weight they achieve. This key question, ‘what happens when we stop using these drugs’ is often left unaddressed by users. Apart from the economic loss and weight regain, those stopping these medications can face psychological issues like the aggravation of a binge eating disorder or even a lack of enjoyment of food, as an online user says ‘I miss enjoying food, I hate it now.’
Personal injury firms are taking notice of the growing numbers of disgruntled users. A blog posted by such a firm points out the high incidence of gall bladder complications, sometimes resulting in the need for surgery, associated with semaglutide use. Class action lawsuits cannot be far behind. Aside from more serious consequences, there is recognition of undesirable cosmetic changes occurring, such as Ozempic face, described as a thin, haggard facial appearance due to loss of sub cutaneous facial fat.
Should Ozempic be Prioritized for Diabetics Only?
With the GLP-1 craze snowballing into a nationwide shortage of all major GLP drugs, the well-being of millions of diabetics is now endangered. The shortage has forced many patients to search several different pharmacies and distributors to get their medication, while others have had to ration what they have and still others have had to go without.
On a popular on-line forum, Mitchell aged 39, revealed he has been using Ozempic for 3 years for treatment of his Type 2 diabetes and is now worried. He states, “I have three children that I want to see grow up, Ozempic has helped me manage my blood sugar.” A shift in prescribed dose, a change of job or even a global shortage can cause the insurance company to withdraw coverage. What formerly cost Mitchell $5 a month is now costing him $1000, when he lost his insurance.
Is Biased Advertisement Adding to the Craze?
Although off-label prescribing is legal, advertising for off-label use is considered illegal. Exactly what elements differentiate an advertisement from legitimate reporting, is complex. During the nationwide GLP-1 shortage, CBS’s 60 minutes aired a segment on Wegovy and according to the TGA, the Australian equivalent of the FDA, the documentary failed to include meaningful mention of alternatives to this medication or potential side effects in violation of the requirement for an advertisement. The TGA went on to warn that advertising Ozempic for weight loss without adhering to these guidelines could be punished by jail time and up to a $1 million penalty in Australia.
Bootlegged and Generic Semaglutide Products
Generic drug makers are hoping to find a way to muscle into the windfall profits generated by this class of medication. The major pharmaceutical companies are prepared to fight to maintain their product dominance. Novo has already launched a lawsuit against 6 generic drug makers to prevent them from producing less expensive GLP-1 look-a-like products.
Further afield from traditional avenues for making and selling medications, the GLP-1 craze has fostered the emergence of so-called bootleggers, marketing their weight loss wares on a smaller scale. Many of these bootleggers are compounding pharmacies which are not FDA regulated. They appear to obtain semaglutide from non-traditional sources then add a vitamin or supplement to it and sell it in single dose vials. Most board-certified endocrinologist and obesity specialists voice deep concern for the quality, efficacy, and safety of these products.
In the chaotic market for GLP-1 agents, a wide range of individuals and small companies have entered the frenzy for profits. One such extremely popular company, with more than 25,000 members uses Trulicity as an active drug in their one-year metabolic reset program to reduce weight.
Finally, while GLP-1 drugs are under fairly strict regulation in the USA and UK, in countries like Thailand, they are easier to obtain. Even now a simple google search can get you a month’s supply for less than 200 dollars, which explains how young girls are getting their hands on a prescription-only drug.
Ana Maria Kausel, described as a New York-based endocrinologist and entrepreneurial physician who is launching an endocrinology telemedicine startup advises doctors to prescribe Mounjaro off-label. She states, ‘some patients eat 800 or 1,000 calories per day, and still don’t lose a single pound, it’s sad. I think doctors should have a lower threshold to prescribe these medications as they are super safe’. Eli Lilly the manufacturer of Mounjaro, started offering coupons and according to Dr Kausel, these drugs are available at cheaper prices overseas, so anyone who can get their hands on it should do it fast, as she believes ‘if it helps lose weight, its completely worth it’.
Modern drugs intended originally for treatment of Type 2 diabetes, can help in weight loss, but are not consequence-free. The casual use of off-label GLP-1 drugs for weight loss is raining havoc on people with diabetes, endangering millions of lives worldwide. At the same time, the wide spread off-label use of these medications by young people is undermining the lifestyle message which is essential for life long weight control.
As stated previously in metabolism.com, the rampant use of anti-obesity drugs has occurred episodically since the 1950s with the latest wave in full swing now. Should physicians and manufacturers just blindly prescribe and market these medications? Or is now the time to look at things from a different perspective. Stay tuned to our website for more exciting revelations coming your way!