Semaglutide

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Structure of semaglutide.
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An Ozempic injection pen.

Semaglutide is the active ingredient in certain drugs taken as pills or injections, to treat diabetes (primarily[1]), obesity,[2] or not yet looking like a Tim Burton character.[3][4] For diabetes, it's prescribed under the brand names Ozempic (injection) or Rybelsus (pills), and for weight loss as Wegovy (injection).[2] According to the manufacturer (Novo Nordisk), these all come "with different indications, dosages, prescribing information, titration schedules, and delivery forms … The products are not interchangeable".[5] As of 2023, no generic versions had been approved by the FDA.[6]

Semaglutide is a glucagon-like peptide-1 (GLP-1) agonist, meaning it mimics the GLP-1 hormone usually released by one's intestines in response to eating food.[2][7] This helps type 2 diabetics when it reduces blood sugar. It helps for weight loss because it suppresses appetite and slows stomach digestion.[7][4] Randomized controlled trials (RCTs) suggest the drug also reduces risk of death from cardiovascular disease in either group.[8][9][10]:3

The drug is not meant as a "miracle drug" for these conditions, being more of an assistant to other treatment strategies.[7] Nonetheless, the expensive drug is touted by Hollywood and social media as an easy weight loss method.[11][5] Many people instead find the common side effects like diarrhea, nausea and vomiting too difficult to bear, and cease treatment before achieving "clinically meaningful weight loss".[12]

The drug's use as a weight loss assistant has caused shortages, including for diabetic people whose condition is typically more urgent to treat although obesity can also be life-threatening,[5][13][10]:2 and the pharma companies themselves may have contributed to the drug's scarcity via advertising campaigns.[5] The demand has resulted in Novo Nordisk being, at times, the highest-valued company in the entire European Union.[14] The Danish company's controlling shareholder, the Novo Nordisk Foundation, states its intent to reinvest profits into "philanthropy, in the form of research, grants, education and even sometimes investments", e.g. stem cell research.[15][16]

Problems[edit]

“Obesity is an epidemic,” cautioned Dr. Zhaoping Li, chief of clinical nutrition at the David Geffen School of Medicine at UCLA. “The issue is that this is one of the tools in our box, it is not the end-all. The longest study done on these injections was conducted over less than two years. A lot of questions have not been answered.”
Dr. Li added that the maximum weight loss exhibited in most patients is 15% of body mass, bringing us back to the awful truth that the resourceful people of Hollywood are loathe to hear: “It comes down to lifestyle. Activity, eating right, and stress management.”
Variety (2022)[11]

Gastrointestinal issues like nausea, vomiting, and diarrhea have been reported as common side effects since some of the earliest RCTs with semaglutide as a weight loss treatment, combined with exercise and dietary coaching; said trials have found the drug effective for weight loss when combined with those.[17] So-called "Ozempic face", that being sagging skin on the face, can also happen. It's attributed to the drug (for which it earned a place in Internet meme canon[3]), though it can actually occur as a result of any quick weight loss.[4] It is suggested that makeup would be a cheaper option for Corpse Bride cosplayers.[citation NOT needed]

Duckhead.gif Quackwatch says: [12]
Patients commonly discontinue semaglutide weight-loss treatment. An analysis of nationally representative, commercial insurance data has found while prescriptions of semaglutide drugs for weight management have increased exponentially, many patients discontinued the drugs before achieving clinically meaningful weight loss.[10] Key findings include:
  • about half the patients who received prescriptions stayed on treatment for a minimum of 12 weeks, enough time to achieve clinically meaningful weight loss
  • 30% of patients discontinued treatment within four weeks, before reaching the targeted dose
  • patients aged 35 and older were more likely to stay on GLP-1 treatment for at least 12 weeks
  • patients who regularly visited their healthcare providers were more likely to stay on the drugs

The report notes that almost all new users of the drugs suffer some gastrointestinal side effects. Patients often stop treatment due to difficulty coping with vomiting, nausea, and diarrhea.

Not to FUD the drug — but it's clearly a commitment.

Shortages, fakes, and "alternative" forms[edit]

Although approved for weight loss in cases of obesity and sometimes overweight when additional health problems related to excess weight occur,[2] the semaglutide has also been sought after by people who want to lose weight for "cosmetic" purposes, which has helped to fuel shortages.[5] The shortages have also led people in both categories to seek out "compounded" alternatives which may not be up to standard and could in some cases contain different active ingredients such as "salt formulations" of semaglutide, i.e. semaglutide sodium and semaglutide acetate.[2] In the United States, these compounded versions are regulated at the state level rather than by the US Food and Drug Administration (FDA).[18] The FDA says:

FDA has received adverse event reports after patients used compounded semaglutide. Patients should not use a compounded drug if an approved drug is available to treat a patient. Patients and health care professionals should understand that the agency does not review compounded versions of these drugs for safety, effectiveness, or quality.[2]

As of 2024, the FDA was investigating allegations of counterfeit semaglutide sold online.[2] Some reports suggest the drug has been incorporated by online scammers promising big discounts, especially if paid in cryptocurrency — just like your real doctor asks for![12][19] Penis enlargement suddenly has some competition in the spam market.

Eating disorders[edit]

A cohort study concluded semaglutide's use for binge eating disorder (in which somebody has excessive urges to eat) warranted investigation,[20] which makes intuitive sense given it suppresses appetite. Though, non-pharmaceutical strategies exist and may be pursued first.[21]

Some (non-)food for thought, quoted in part:

Emerging research strongly supports that for many, eating disorders are brain-based illnesses and in most cases, there exists a co-morbidity like anxiety, mood disorders, or substance abuse.

“GLP-1’s can’t help someone deal with their stress, anxiety, [and] trauma-history,” said psychologist Cynthia Bulik, one of the world’s leading eating disorder researchers, and Founding Director of the University of North Carolina Center of Excellence of Eating Disorders. “All of that background distress—fundamental distress that might be driving the BED in the first place—is temporarily bypassed by removing the desire to eat.”

… Further, these drugs are often intended to be taken for a person’s entire life. “When they go off the drug, or can’t access it due to supply problems, the urge to binge comes right back and they have not developed any psychological (or) behavioral skills to manage the urge,” Bulik told me. Just like with a diet, any lost weight will likely be regained when a person stops taking the drugs. Weight fluctuations, themselves, may increase a person’s risk of chronic illnesses like type 2 diabetes, according to multiple studies.

“The focus on weight and erasing the desire to eat could indeed do harm,” cautioned Bulik. “The potential for abuse is high and will become higher with new preparations that don’t require an injection … Remember, these drugs are ‘for life.’ Stop them, and everything comes rushing back.”[22]

(There can be "feedback loop" situations between body shame and overeating,[23] and so it's hard to entirely rule out such an option to break a vicious cycle, but there may be better ones.)

See also[edit]

External links[edit]

References[edit]

  1. Steven Novella (June 28, 2023). "Does Intermittent Fasting Work?". Science-Based Medicine. "There are medications available, such as Ozempic. These are primarily for diabetes, but are shifting to treatments for obesity itself. However, these medications are expensive and have to be taken indefinitely, with a risk of rebound if they are stopped. Medical interventions therefore have a role to play, but they are not for everyone."
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 (January 10, 2024). "Medications Containing Semaglutide Marketed for Type 2 Diabetes or Weight Loss". Food and Drug Administration.
  3. 3.0 3.1 "Ozempic Face". KnowYourMeme.
  4. 4.0 4.1 4.2 Lisa Catanese (February 5, 2024). "GLP-1 diabetes and weight-loss drug side effects: "Ozempic face" and more". Harvard Health Publishing.
  5. 5.0 5.1 5.2 5.3 5.4 Sydney Lupkin (July 10, 2024). "Ozempic's popularity leads to shortages for people with Type 2 diabetes". Health Shots (NPR).
  6. (July 19, 2023). "Ozempic for weight loss: Does it work, and what do experts recommend?". UC Davis Health.
  7. 7.0 7.1 7.2 (July 3, 2023). "GLP-1 Agonists". Cleveland Clinic.
  8. Lincoff, A. Michael; Brown-Frandsen, Kirstine; Colhoun, Helen M.; Deanfield, John; Emerson, Scott S.; Esbjerg, Sille; Hardt-Lindberg, Søren; Hovingh, G. Kees et al. (2023-12-14). "Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes". New England Journal of Medicine 389 (24): 2221–2232. doiWikipedia:10.1056/NEJMoa2307563. ISSN 0028-4793. 
  9. (August 30, 2024). "New Science Suggests Semaglutide Improves CV Outcomes Beyond Weight Loss". American College of Cardiology.
  10. 10.0 10.1 10.2 Real-world trends in GLP-1 treatment persistence and prescribing for weight management. Blue Health Intelligencer Issue Brief, May 2024
  11. 11.0 11.1 Matt Donnelly (September 21, 2022). "Hollywood's Secret New Weight Loss Drug, Revealed: The Hype and Hazards of Ozempic". Variety.
  12. 12.0 12.1 12.2 (June 16, 2024). "Consumer Health Digest, Issue #24-24". Quackwatch.
  13. Stephen Fairclough (September 6, 2023). "Ozempic shortage hits diabetes patient after weight loss use". BBC News.
  14. Euan Healy (September 4, 2023). "Weight-loss drug maker Novo Nordisk becomes Europe’s most valuable company". The Financial Times.
  15. Hannah Kuchler (December 26, 2023). "How anti-obesity drugs built the world’s largest charitable foundation". The Financial Times.
  16. James Waldron (October 6, 2023). "Flush with Wegovy cash, Novo Nordisk's owner widens investment strategy beyond biotech". Fierce Biotech.
  17. Harriet Hall (April 6, 2021). "A New Medication to Combat Obesity". Science-Based Medicine.
  18. Anna Claire Vollers (July 8, 2024). "‘Compounded’ weight-loss drugs are a growing problem for state regulators". Stateline (States Newsroom).
  19. Abhishek Karnik (June 12, 2024). "How Ozempic Scams Put People’s Finances and Health at Risk". McAfee.
  20. Richards, Jesse; Bang, Neha; Ratliff, Erin L.; Paszkowiak, Maria A.; Khorgami, Zhamak; Khalsa, Sahib S.; Simmons, W. Kyle (2023-09-01). "Successful treatment of binge eating disorder with the GLP-1 agonist semaglutide: A retrospective cohort study". Obesity Pillars 7. doiWikipedia:10.1016/j.obpill.2023.100080. ISSN 2667-3681. 
  21. Casey Kuhn (September 25, 2023). "Patients say drugs like Ozempic help with ‘food noise.’ Here’s what that means". PBS NewsHour.
  22. Cole Kazdin (April 16, 2024). "Ozempic Hurts the Fight Against Eating Disorders". TIME.
  23. O’Loghlen, Elyse; Galligan, Roslyn; Grant, Sharon (2023-06-13). "Childhood maltreatment, shame, psychological distress, and binge eating: testing a serial mediational model". Journal of Eating Disorders 11 (1): 96. doiWikipedia:10.1186/s40337-023-00819-7. ISSN 2050-2974. PMID 37312168.