This is a bonus article that will not be included in my weight loss book, unless I decide to update it with a second edition.
Casey Arnold, who lives in a suburb of Houston, spent years trying to quit smoking. She’d tried nicotine patches. That failed. She tried quitting cold turkey but that made her short tempered. On other occasions the idea of quitting made her so anxious, she smoked more to ease her fears.
By the time she permanently gave up cigarettes in the winter of 2023, at age 55, she’d been smoking for four decades and was up to two packs a day. But this time it was a new type of weight loss drug that helped her quit.
GLP-1, short for glucagon-like peptide 1, is a natural hormone that stimulates the production and release of insulin, slows digestion, curbs appetite, and blunts the brain’s focus on food. GLP-1 agonist drugs, like exanetide, tirzepatide and semaglutide, mimic this hormone. They were originally developed as diabetes treatments, but as more people began taking them, researchers observed these medications are effective for many more conditions than just diabetes and weight loss.
The FDA recently approved semaglutide, the active ingredient of Wegovy, for the treatment of obesity and for reducing the risk of heart attack and stroke in patients with obesity and heart disease. But as the number of people taking these drugs grows, physicians and researchers are learning about unanticipated health benefits for conditions where treatments have been limited, such as addiction, heart failure, and kidney disease.
Arnold quit smoking while participating in a clinical trial examining the potential of GLP-1 agonists as a treatment for smoking addiction.
“It was totally opposite of when I tried to quit in my previous years,” Arnold says. “I was shocked at how calm I was, compared to how I used to think about quitting.” Instead of anxiety and rage, she felt at peace, and her cravings faded.
“It’s just been an avalanche across the different patient populations,” says Mark Petrie, a cardiologist at the University of Glasgow, whose research focuses on the use of GLP-1 agonists in patients with heart failure. “It’s just good news all around.”
Heart failure with preserved ejection fraction
More than six million Americans are living with heart failure, a condition where the heart progressively loses the ability to pump enough blood to the rest of the body. Of these patients, approximately half have a type known as heart failure with preserved ejection fraction, in which the heart can pump normally but is too stiff to fill up with blood.
In a study published last year, researchers tested semaglutide as a treatment for heart failure with preserved ejection fraction in patients who were not diabetic. The result: patients who received the drug showed fewer symptoms and reported a better quality of life, compared to those who received the placebo. Patients who received the drug had lower levels of C-reactive protein, which is a marker for inflammation.
“This is a big finding,” says James de Lemos, a cardiologist at UT Southwestern Medical Center, in Dallas, Texas, who was not associated with the study. The study was too small to determine if semaglutide can reduce the risk of hospitalization or death but given the stark improvement in patient quality of life, it’s promising.
Although some of these benefits are likely due to weight loss, that’s just part of what makes this treatment effective.
These medications are also cardioprotective and reduce inflammation, which is known to be a driver of heart failure, says Amanda Vest, a cardiologist at the Cleveland Clinic, who specializes in treating patients with heart failure. “We must continue to think more expansively than just about the number on the scale,” Vest says.
For patients with the other major type of heart failure—heart failure with reduced ejection fraction—there is less evidence, so far, that these drugs are effective. More trials are in the works to determine which types of patients will benefit from the use of these medications.
Kidney disease
An estimated 850 million people worldwide are living with chronic kidney disease, but there are few effective treatments. Historically, the main strategy has been to stall kidney failure for as long as possible and then move the patient to dialysis or wait for a kidney transplant. But nine out of 10 patients die of complications before reaching that point.
For patients with severe chronic kidney disease, “you are looking at a mortality rate that’s 10 to 20 percent a year,” says Katherine Tuttle, a nephrologist at the University of Washington Medicine. “This is on par with the worst malignancies.”
As a couple of recent studies have shown, the GLP-1 agonist dulaglutide helps patients who suffer from chronic kidney disease and diabetes. In a recent trial looking at the effect of semaglutide on patients with chronic kidney disease and type 2 diabetes, the treatment was so effective at delaying the progression of chronic kidney disease that the clinical trial was stopped early so that all the trial patients could benefit from the drug.
“It’s the only semaglutide trial that was stopped early for efficacy,” says Tuttle, who is on the executive committee for the trial. “To stop a trial early for efficacy, the bar is set really high,” which includes strong enough evidence for its efficacy that it would be no longer considered ethical to continue giving patients the placebo.
As Tuttle notes, the effects on the kidneys is only partially due to reductions in risk factors such as blood pressure, blood sugar, and weight. Other benefits are likely to result from reduced inflammation.
“They have a profound anti-inflammatory effect,” Tuttle says. “Our field is really under recognizing the importance of inflammation, particularly in kidney damage caused by diabetes.”
Results from the trial will be published later this year.
Effects on fertility
For a growing number of patients on GLP-1 agonists, such as Ozempic or Mounjaro, one surprising side effect has been unexpected pregnancy, which for some patients, has come after years of struggling with infertility. Although more research is needed to explore the link between GLP-1 agonists and pregnancy, it’s become enough of a phenomenon that ‘Ozempic babies’ has become a trending phrase. Meanwhile, experts think there are several factors responsible.
The first factor is the fact that GLP-1 agonists cause a delayed gastric emptying, which can cause oral contraception pills to be absorbed by the body at a slower rate. “These drugs are altering that particular part of the drug absorption phase,” says Archana Sadhu, an endocrinologist at Houston Methodist Hospital, adding that this effect can be particularly prominent during dosage increases. This means that oral birth control may not be as effective.
The second factor is the link between polycystic ovarian syndrome (PCOS)—the leading cause of infertility in women—and insulin resistance.
“Insulin resistance will dysregulate the ovarian cycle,” Sadhu says. Insulin resistance can lead to infertility by disrupting hormones such as estrogen and testosterone, which are related to fertility; and it can affect the release of eggs from the ovaries. When patients start taking GLP-1 agonists, this reduces their insulin resistance, which boosts fertility.
However, the effects of these drugs on pregnancy are still unknown, which means that it’s important for patients to talk with their doctors about any plans for becoming pregnant, as well as strategies for contraception, which may include adding in a second method to augment oral contraceptive pills, or switching to a different method.
Treating addiction
Since Ozempic and Mounjaro have been become more common, patients have been reporting several unexpected side effects, such as a diminished desire to smoke or drink. Although more research is needed, it’s thought that the part of the brain that is responsible for food cravings overlaps with the part of the brain that is responsible for cravings for substances of abuse, says Luba Yammine, an addiction researcher at UTHealth Houston.
For doctors working in the field, earlier versions of these GLP-1 drugs showed tremendous potential as anti-addiction medications.
“We have far fewer medications available” for treating addiction and many patients report difficulties accessing these, says Christian Hendershot, an addiction researcher at the University of North Carolina School of Medicine. The field also receives less research funding compared with other diseases.
For Yammine, she first became interested in studying the effect of GLP-1 agonists on addiction while working in primary care, where she had several patients who were smokers with diabetes. Yammine would counsel her patients on quitting smoking, prescribing nicotine patches or the medication buproprion, to help them quit. But most of the time these strategies failed.
“It’s hard to quit smoking, period,” Yammine says. “The vast majority of smokers want to quit, but even with the use of these therapies, many of them are not successful.”
To help these smokers with their diabetes she would prescribe GLP-1 agonist medications, only to discover when they returned for a follow-up that they had quit smoking. When she asked them what happened, their answer was that suddenly their cravings vanished. “That was a very interesting finding,” Yammine says.
This happened often enough that Yammine decided to explore the impact of these GLP-1 receptor agonists on addiction through a clinical trial.
Yammine and her collaborators led a pilot study, in which 46 percent of the participants who received exanetide, plus nicotine patches and smoking cessation counseling, were able to quit, compared to 26 percent of participants who received nicotine patches, counseling, and a placebo. Yammine and her collaborators are now following up with a larger trial. They are also planning a separate trial with semaglutide.
For the patients in the study who received exanetide, their post-cessation weight was 5.6 pounds lower than those who received the placebo, a side effect that can help offset the weight gain that is often associated with quitting smoking.
“This weight gain is very problematic,” Yammine says, adding that many patients are either afraid to quit or relapse due to concerns about weight gain, while it can also put them at heightened risk for developing weight-related conditions, such as type 2 diabetes.
For Arnold, who was enrolled in a follow up trial that Yammine is conducting, the months in which she was participating in the trial was characterized both by a calmness surrounding her efforts to quit, as well as minimal weight gain. Since the trial has ended, she’s been able to maintain her efforts to quit smoking, although she gained a little weight. “I don’t have cravings,” Arnold says. “It’s this weight gain that is bothering me.”
Arnold, who works for an HVAC company, would really like to go back on exanetide, but as is the case with so many other patients who have experienced benefits from GLP-1 receptor agonists, she’s finding that it’s too expensive to do so. Just one month’s supply costs about $1,000, and without FDA approval for its use as an anti-addiction drug, most health insurance companies won’t pay for it.
New obesity drugs are coming. Here’s how they could change everything.
A steady stream of weight loss drugs, which mimic naturally occurring hormones, are in the pipeline. This competition may finally lead to lower prices and greater supplies of these highly effective drugs, and maybe replace some injectables with pills.
The recent approval of another obesity drug, Zepbound, expands the options for medications to manage weight, but it comes with the same cost and access challenges that plague other weight loss drugs in its class.
The drugs in this class are agonists, or mimics, of natural gut hormones that affect the body’s metabolism and hunger signals in the brain. But the currently approved drugs, synthetic versions of these hormones, are large molecules that are expensive and time-consuming to manufacture, which has meant high prices for consumers and growing drug shortages. Further, most of these drugs are injections, rather than oral pills, and usually require refrigeration for storage. With more than four in 10 Americans—and nearly 2 billion people worldwide—affected by obesity, the promise of these new drugs to treat the world’s fastest growing chronic disease has been clashing with the reality of their cost and access problems.
In addition to the complex manufacturing, the small number of obesity drugs on the market has meant less competition, driving up prices for consumers. That’s a problem as many private health insurance plans still do not cover obesity medications. Although researchers are developing oral versions of these medications—including versions that are cheaper and faster to make and distribute—those aren’t yet ready for review by the U.S. Food and Drug Administration, and the existing oral medications aren’t as effective as the injections.
“The big issue is the fact that right now, not only are the drugs expensive, but it’s also difficult to get injections to places where people may need them,” Ali Zentner, a weight management physician and medical director of Revolution Medical Clinic in Vancouver, Canada, says. “And in the United States, for example, equity depends on your income and your insurance—it doesn’t really matter where you are.”
However, a half dozen or so candidates in this same drug class have been making their way through clinical trials, and as several of them are on track to head to the FDA in the next few years, experts hope they will finally begin expanding access so the world can begin making progress on addressing the obesity epidemic.
One drug in development that has been turning heads is orforglipron, a drug like the already approved agonist drugs but which is a smaller molecule, making it easier and cheaper to produce. It’s also an oral pill, not an injection, which is not as sensitive to storage temperature as injectable medications are. Though only just entering phase 3 studies, the effectiveness seen from orforglipron in a phase 2 trial suggests that a more accessible option is not out of reach.
Existing medications are “in a form that we can use easily, but we can’t make an injectable all that easily,” says Sean Wharton, an adjunct professor at McMaster University and medical director of the Wharton Medical Clinic who is leading the research on orforglipron. “To have something that you have to take every week for the billions of people across the planet that are living with obesity means that you need a product that can get there, that can be mass produced, and then given out in an appropriate fashion.”
A confusing collection of weight loss drugs
The rapid pace of approvals for this new drug class has led to a dizzying list of names that can be difficult to track.
A major reason for the confusion is that the FDA approves the same chemical drug for different conditions, and companies give different brand names to the drug based on the condition it treats.
Many people have heard of Ozempic, the brand name for semaglutide, which is approved for type 2 diabetes. That same compound, semaglutide, is also approved to treat obesity and goes by the brand name Wegovy.
Another major drug in this class is tirzepatide, which is approved for type 2 diabetes as Mounjaro, and for obesity as Zepbound.
Zepbound’s approval last month came after clinical trials showed people with obesity lost up to 21 percent of their body weight with the highest dose.
With the pace of these approvals matched only by demand for them, what hasn’t kept up is access to these medications, primarily due to drug shortages and their cost.
Shortages of Mounjaro, which costs $1,023 per month without insurance, are already expected to last through August, 2024. Its competitor, Ozempic, costs $936 and is also limited. Those supply issues are expected to carry over to Zepbound (same compound as Mounjaro) and Wegovy (same compound as Ozempic)—and are similarly expensive. Zepbound’s price is $1,060; Wegovy’s, $1,349.
A new class of drugs
Ozempic was not the first of this new class of drugs to hit the market, but it was the first to become a household name as celebrities shared their weight loss success from its off-label use on social media. It was also the most effective drug of its kind when it was approved as Wegovy for obesity in 2021.
But all of these drugs, called GLP-1 agonists, are injectable medications that mimic the effects of glucagon-like peptide-1 (GLP-1), a gut hormone that stimulates the release of insulin. And over the near-decade since the first GLP-1 agonist was approved for obesity in 2014, scientists have learned enough to begin expanding their research to include other gut hormones.
“This is new science, and this is coming from someone who has been in this field for over 40 years,” says Robert Kushner, an endocrinologist at Northwestern University’s Feinberg School of Medicine in Chicago, who consults for some of the companies developing these drugs. “As we start to harness the power of these intestinal and pancreatic hormones individually and as combinations, we are really learning along the way.”
While these new drugs definitely have side effects—some of which can be serious—they are biologically completely distinct from the less-than-stellar legacy of past weight loss drugs.
“We’re now, for the first time, understanding that, in part, the gateway to regulating appetite and treating the dysregulation of appetite is through these gut hormones,” Kushner adds.
Zepbound is the first obesity drug to exploit more than one gut hormone: it mimics both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), another hormone involved in metabolism that plays a role in obesity. But GLP-1 and GIP are just two of the dozens of gut hormones that affect digestion and other metabolic processes.
As scientists learn more about the functions of other gut hormones, they are testing drugs that mimic those as well. Many of the newer drugs coming down the pipeline mimic two or three gut hormones, such as GLP-1, GIP, and glucagon.
It often happens in medicine that one or two agents of a certain drug class are development and then the class opens up more, Zentner says. “We are on the precipice,” now that researchers understand the biology of these various hormones, she says. “We’ve cracked the code of GLP, GIP, glucagon,” and other gut hormones, so now scientists are testing what happens when they combine multiple synthetic versions in one drug.
Ozempic is a serious drug with serious risks. Here’s what to know.
The diabetes medication semaglutide has recently become a trendy weight loss treatment. But like every drug, there are downsides—and potentially serious side effects.
Billionaire Elon Musk credited it for his dramatic weight loss. Celebrity sites allege that many more A-listers are using it to stay trim. And TikTok is full of influencers showing off their startling before-and-after shots showing off their weight loss after using it.
What is it? A medication called semaglutide, which is sold under different brand names, including Ozempic, approved in 2017 for treating type 2 diabetes, and Wegovy, approved just last year for weight loss.
The buzz about these drugs has created a shortage of both, according to the U.S. Food and Drug Administration, which is expected to last for several months—causing alarm among patients with diabetes who rely on Ozempic to help control their blood sugar. Experts caution that it’s important to understand these are not miracle drugs—and that there are risks to taking them outside of their intended use.
ere’s what you need to know about semaglutide, including how it works and the risks.
What’s the science behind the drug?
Semaglutide helps lower blood sugar by mimicking a hormone that’s naturally secreted when food is consumed, says Ariana Chao, assistant professor at the University of Pennsylvania School of Nursing and medical director at the school’s Center for Weight and Eating Disorders. This medication, administered through injection, helps people feel full for longer, helps regulate appetite, and reduces hunger and cravings.
There is significant demand for the drug. In 2019, more than 11 percent of the population was diagnosed with diabetes, while more than four in ten adults classified as obese in 2020.
Patients with type 2 diabetes often have impairments in insulin, a hormone that helps break down food and convert it into fuel the body can use, Chao says. Semaglutide signals the pancreas to create more insulin and also lowers glucagon, which helps control blood sugar levels. This can result in weight loss but experts point out that Ozempic has not been approved for that purpose, though semaglutide at a higher dose (Wegovy) has been.
Wegovy is the first drug since 2014 to be approved for chronic weight management. The difference between the two drugs is that Wegovy is administered at a higher dose of semaglutide than Ozempic. Wegovy’s clinical trials showed more weight loss but only slightly greater improvements in glycemic control compared to Ozempic, Chao says.
The FDA sees Ozempic and Wegovy as two different medications for different uses. Chao says many insurance companies cover Ozempic for diabetes but don’t cover Wegovy for obesity—a prime example of weight bias in health care. That’s why some medical providers use the two doses somewhat interchangeably, as obesity and type 2 diabetes are inextricably linked–obesity is the leading risk factor for developing type 2 diabetes.
What are the risks?
Like every medication, there can be downsides.
The most common side effects are gastrointestinal issues, such as nausea, constipation, and diarrhea, Chao says—and more rarely, pancreatitis, gallbladder disease, and diabetic retinopathy.
Angela Godwin, nurse practitioner and clinical assistant professor at the NYU Rory Meyers College of Nursing, explains that recent reports of extreme vomiting and gastroparesis (delayed emptying of the stomach) are to be expected.
Gastroparesis “just means the food’s in your stomach longer, which then makes you feel fuller longer,” she explains.
Nausea is one of the biggest side effects of medications like Ozempic and Wegovy, and that can always lead to vomiting, Godwin says. In June, the American Society of Anesthesiologists recommended patients stop taking these medications before surgery to avoid aspiration and vomiting.
“Normally, in my experience, it’s tolerable,” she says. “But then there are times when I ask [patients], ‘Well, what happened?’ And they [say] they ate too much and ate too quickly. And then yes, the body will vomit it up, because it just can’t tolerate that much food anymore.”
These drugs have been extensively studied, but their relatively recent approval means researchers still don’t know what the effects of taking them long term might be.
Resources
nationaleographic.com, “The unexpected health benefits of Ozempic and Mounjaro.” By Rachel Fairbank; nationalgeographic.com, “New obesity drugs are coming. Here’s how they could change everything. A steady stream of weight loss drugs, which mimic naturally occurring hormones, are in the pipeline. This competition may finally lead to lower prices and greater supplies of these highly effective drugs, and maybe replace some injectables with pills.” By Tara Haelle; nationalgeographic.com, “Ozempic is a serious drug with serious risks. Here’s what to know. The diabetes medication semaglutide has recently become a trendy weight loss treatment. But like every drug, there are downsides—and potentially serious side effects.” By Allie Yang;
Weight Loss Articles
https://common-sense-in-america.com/2023/04/12/losing-weight-leads-to-better-health-not-necessarily/
https://common-sense-in-america.com/2023/04/25/hormones-that-control-your-appetite/
https://common-sense-in-america.com/2024/07/02/the-unexpected-health-benefits-of-ozempic-and-mounjaro/