Weight Loss? No Easy Answers

"Usually when a new medicine happens, we have time to learn how to use it. [But with GLP-1 drugs], everyone is kind of iterating in real time." 

"For the first time, we have medications that target obesity at its root, reshaping how the brain and gut regulate hunger and impact metabolism. These breakthroughs are game-changing, but major barriers remain: high costs, insurance hurdles, lack of real-world data in diverse populations, and persistent stigma."

"Both of them [Ozempic and Wegovy] slow stomach emptying. Both of them decrease appetite. Both of them work at the level of the pancreas and at the level of the brain and other organs in the body."

"It is a blockbuster in the works. [The weight loss it produces is] profound [and might be a good fit for people with a very high BMI]."

Dr. Melanie Jay, director, N.Y.U. Langone Comprehensive Program on Obesity 

 

"Not everybody responds to GLP-1." 

"[Other] people are having tolerance to it. … Over time, somebody who responded to Wegovy really well at the beginning, five, 10, 20 years from now, probably will need some other more powerful or different acting medication."

"For somebody who has a lower BMI of 30, this might be overpowering."

Dr. Shauna Levy, medical director, Bariatric and Weight Loss Center, Tulane University, New Orleans 

 

"Just as there are many classes of medications for diabetes or for blood pressure, there will be many different classes that target different mechanisms of the disease of obesity."

"They are all hormones that communicate to our brain. How hungry are we? How full are we?"

Dr. Ania Jastreboff, director, Yale Obesity Research Center

Alvvino

 

World-wide, tens of millions of people take prescribed drugs like Ozempic. A situation that represents a type of real-time experiment offering substantially greater data than would be the case with even carefully controlled clinical trials. Originally prescribed as a weight-loss drug for people with diabetes, the drug has greatly expanded in use beyond diabetes and obesity. Some of the class have been approved for the new purpose of reducing risk of heart attacks and allied cardiovascular issues as well as for the treatment of sleep apnea, severe liver disease, and kidney disease.

 

While the drugs' use has been expanded now to treat a wider variety of health conditions, it is widely acknowledged that it is their weight loss performance that drives their wider use. On the other hand researchers subscribe to the belief that the drugs provide benefits other than weight loss. Leading that  belief is a theory that the drugs' effect diminishes the opportunities for inflammation, involved in many chronic health conditions.

 

Those patients who decide to cease taking the drugs tend to regain weight to a significant degree. Clinical trials of the injectable drugs now in circulation have noted that people lose some 15 to 20 percent of their body weight on average after roughly 72 weeks; numbers supported by other studies. Depending on the drug and the study other real-world  trials indicate average weight loss to range between 8 and 17 percent. 

 

When people  decide to stop taking the drugs it is most often attributed to the result of unwanted side effects, or the costs involved. At least some of the dropped weight will be regained. Records of 180,000 patients underwent an analysis that found over half of those who took semaglutide -- the working substance of Wegovy -- or tirzepatide -- the compound in Zepbound -- retained at least some lost weight or even additional weight two years post-cut-off. 

 

GLP-1 drugs for diabetes and weight loss have proven to be very effective, but they do have side effects. Among those side effects is "Ozempic face," where skin on the face sags and wrinkles. "Ozempic face" was coined in reference one of these drugs, although any rapid weight loss can cause it. Harvard Health

 

Patients stopping use of the drugs frequently select other methods to maintain weight loss, including intense exercise, bariatric surgery or other weight-loss medications, according to Hamlet Gasoyan at the Cleveland Clinic in Ohio, who studies these drugs. Unexpected downsides can result with many people on the drugs experiencing side effects reported in clinical trials, such as nausea, fatigue and digestive issues like vomiting and diarrhea.

 

With ever greater numbers making use of the drugs, additional concerns crop up, such as "Ozempic breath" (dehydrated patients whose dampened appetites cause them to consume fewer liquids), and "Ozempic face" that results after fat loss leaves a hollowed-out appearance on the face. More serious issues have also emerged with doctors seeing dialled-down appetites sufficiently extreme to end up with some patients developing nutritional deficiencies.

 

The loss of muscle mass in some patients, another issue -- with many young, healthy patients able to recover or preserve muscle by strength training and consuming more protein, according to doctors. Older adults, however become more frail on these medications, and the risk of falls becomes more troubling. There are some who use the drugs who claim to feel more confident, able to exercise and move about with greater ease. 

 

Other patients claim, according to Marie Spreckley, a researcher at University of Cambridge, that they feel emotionally flatter, abandoned by the delight they once held for food, leaving them less connected to the social element of eating with others. Even others report personalities that feel dull, or being left feeling lethargic under the influence of the drugs. 

 

For many years, patients struggling with weight loss were told that success simply required more willpower – eat less, exercise more and the weight would eventually come off. But recent advances in medical science prove it’s often not that simple. The Science of Health

 

Boiler-Plate Response to Heightened Drug Toxicity

"[Data from the study are not sufficient to establish a cause-and-effect association between semaglutide and NAION]; key methodological limitations of the study [need to be considered when interpreting the findings]."

"Patient safety is a top priority for Novo Nordisk, and we take all reports about adverse events from the use of our medicines very seriously."

"Semaglutide has been studied in large real world evidence studies and robust clinical development programs with a cumulative exposure including from post-marketing use of over 22 million patient years."

"The totality of data provides reassurance of the safety profile of semaglutide." Novo Nordisk

Semaglutide is most commonly known under the brand names Wegovy and Ozempic. Photograph: Reuters

A new American study has found that drugs containing the active compound semaglutide have a potential side-effect among certain users, presenting a dilemma in outcome.Last summer researchers at Mass Eye and Ear in Boston, Mass felt motivated to begin an investigation on whether the sought-after weight-loss drugs might be associated with increased risk of NAION. Their interest was piqued after three patients were diagnosed with a  relatively rare eye condition.

The study conclusion was that Ozempic and other weight-loss drugs -- so hugely popular -- contain the active compound semaglutide, associated with increased risk of NAION, (nonarteritic anterior ischemic optic neuropathy). An eye-loss condition affecting two to ten in every 100,000 people annually. Sudden and permanent loss of vision in one eye as a result of insufficient blood flow and oxygen to optic nerves. The condition is also referred to as an "eye stroke", a significant cause of adult blindness.

 

Three patients at the Harvard Medical School who took semaglutide were diagnosed within the same week with AION. Published in JAMA Ophthalmology, the study found people who were prescribed semaglutide became seven times likelier to end with a diagnosis of NAION than were people prescribed different drugs for an overweight condition. Semaglutide prescribed for Type 2 diabetes saw people becoming four times more likely to be threatened with the rare eye diagnosis.

 

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"Our main finding is that prescribed semaglutide is associated with an increased risk of NAION", the researchers concluded. "We should be confident that if corroborated, the absolute risk of developing NAION in direct relation to taking semaglutide must indeed be rare", wrote University of Birmingham professor Dr. Susan Molan, who investigates rare diseases of the eye and brain. The findings "should be viewed as significant but tentative", cautioned Dr. Joseph Rizzo, director of the neuro-ophthalmology service at Mass Eye and Ear. 

 

Ozempic and Wegovy are in a class of drugs  called GLP-1 agonists, spurring the release of insulin, and lowering blood sugar, but act as well on the brain to curb appetite. Given through a once-weekly injection by a prefilled pen. A survey by Dalhousie University's Agri-Food Analytics lab, partnering with market research firm Caddle, found some ten percent of the Canadian adult population uses a GLP-1 type drug for diabetes control, weight loss, or both. 

 

Reports of potential unforeseen side-effects inclusive of gastrointestinal problems and unplanned pregnancies have arisen with the growing popularity of the drug. The research team studied records of patients referred to their clinic from 2017 through to 2023, checking for NAOIN diagnoses. Records of close to 17,000 patients treated over six years were analyzed. Among them 629 NAION cases were diagnosed in that six-year period.

 

Divided into two groups those diagnosed with Type 2 diabetes and people living with obesity were separated to compare people who received prescriptions for semaglutide along with those taking other diabetes or weight-loss drugs. Among those with diabetes, 8.9 percent of the semaglutide-treated group developed NAION within three years of follow up, compared to 1.8 percent for the non-semaglutide group.

 

5.7 percent in the semaglutide group of overweight or obese people were diagnosed with NAION, as opposed to 0.8 percent of those prescribed drugs other than semaglutide. 

Some of the most common for semaglutide include:

• nausea
• vomiting
• diarrhoea
• stomach pain
• constipation

 

A box of Ozempic and contents. 

George Frey | Reuters