Month: June 2022

The current shortage of semaglutide (Ozempic), an important diabetes drug, has an unusual origin: too many people without diabetes are taking it. Here’s how that happened, and how we might course-correct to help ensure that those with the greatest need for this medicine can get it.

A diabetes drug with an important side effect: Weight loss

Semaglutide (Ozempic) was first approved by the FDA in 2017 to help people with type 2 diabetes keep blood sugar under control. But during pre-approval studies, researchers noticed a remarkable side effect: people lost weight. For example, in one pivotal study, average losses for those receiving one milligram a week of semaglutide were:

• nearly 10 pounds lost over 30 weeks
• nearly 5% overall body weight lost
• waist size shrank 1.6 inches.

This side effect helped people with type 2 diabetes because excess weight is a major risk factor for the condition. Among other health benefits, weight loss can lower blood sugar and blood pressure, and reduce the need for other diabetes medications.

Turning a side effect into a selling point

Unintended weight loss would usually be listed as a side effect for a study medication. But ads for Ozempic didn’t list it with the other possible side effects; instead, it was featured as a benefit. The Ozempic “Tri-Zone” (a phrase concocted by marketers, not medical experts) promised improved blood sugar control, lower cardiovascular risk, and weight loss.

At the bottom of the ad, fine print that’s easy to miss states: “Ozempic is not a weight loss drug.” Talk about mixed messages!

The makers of Ozempic saw the potential of semaglutide as a weight loss drug for people without diabetes. Sure enough, clinical trials confirmed that overweight and obese people taking semaglutide also lost substantial weight. Semaglutide received FDA approval in 2021 for people with obesity (BMI of 30 or greater), or who were overweight (with a BMI of 27 to 29.9) and had a medical problem related to excess weight, such as high blood pressure or high cholesterol. As a weight loss drug, it was rebranded as Wegovy.

The only difference between the two drugs? The maximum approved dose of semaglutide is a bit higher with Wegovy than Ozempic.

How social media fueled the Ozempic shortage

Soon after the approval of Wegovy, celebrities and social media influencers began taking it and sharing glowing weight loss experiences. What’s more, medicines approved for specific uses in the US can be prescribed off-label for any use: up to 38% of all prescriptions written in the US are off-label (note: automatic PDF download). So, it’s likely some of the viral run on Wegovy was fueled by people who wanted to lose weight but had no medical reason to take it.

After high demand put Wegovy in short supply, many turned to Ozempic to lose weight. And that contributed to a shortage of Ozempic, threatening the health of people with type 2 diabetes who rely on the drug.

Readjust priorities and limit irresponsible prescribing

This situation couldn’t have happened without physicians or other health care professionals willing to write Ozempic prescriptions for people who did not have diabetes or another medical reason to use semaglutide. And that suggests an obvious solution: limit prescriptions for Ozempic to people with diabetes. For many drugs, a prior authorization process requires certain conditions be met before a prescription can be filled. This could be done for Ozempic.

And of course, we should encourage people who don’t have diabetes not to request a prescription for Ozempic. While that message is unlikely to show up in a drug ad, public service announcements could do the trick.

The bottom line

Drug ads often urge you to ask your doctor if a treatment is right for you. But we already know a key piece of the answer for Ozempic: if you don’t have diabetes, don’t ask for a diabetes medicine to help with weight loss. There are better ways to get the help you need to reach a healthy weight if you are overweight or obese. Talk to your doctor about a full range of treatment options. And if your weight is already in a healthy range, it’s not a good idea to take a medication to become thinner.

Finally, to keep vitally important medicines available for those who need them most, health care professionals must prescribe them responsibly. Responsible requests by their patients could help.

About the Author

Robert H. Shmerling, MD, Senior Faculty Editor, Harvard Health Publishing; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Robert H. Shmerling is the former clinical chief of the division of rheumatology at Beth Israel Deaconess Medical Center (BIDMC), and is a current member of the corresponding faculty in medicine at Harvard Medical School. … See Full Bio View all posts by Robert H. Shmerling, MD

Pregnancy is often painted as a time of elation and joy, emotions many people may indeed feel. As doctors, though, it’s hard to ignore the health risks and the fears that can arise in the wake of a positive pregnancy test for some of our most vulnerable patients.

Simply being pregnant poses significant short-term and long-term risks to health, particularly in the US. We have the highest rate of serious pregnancy-related complications among developed nations, resulting in about 700 deaths a year nationally. This health burden is unequally distributed, falling hardest on women of color and low-income women — in fact, Black women are three times as likely to die as white women from pregnancy-related complications.

What makes pregnancy challenging from a health standpoint?

Pregnancy acts as an ongoing stress test that taxes body systems and generates unique health risks. It changes how the heart, lungs, and kidneys function. It also alters the immune system, and changes metabolism through effects on various organs. It increases blood flow throughout the body. The impact is greater for anyone who already has high blood pressure, diabetes, or other health conditions. Additionally, pregnancy can also deepen existing mental health disorders such as depression and anxiety, often exacerbating symptoms.

Two health issues unique to pregnancy are:

• Preeclampsia. This causes high blood pressure and possible damage to other organs, such as the kidneys, liver, and brain. Pregnancy alone places extra stress on the heart and blood vessels. Having a pregnancy affected by preeclampsia more than triples one’s lifetime risk of cardiovascular disease such as stroke or heart attack, according to the Preeclampsia Foundation. The biggest risk factors for developing preeclampsia are being younger than 18 or older than 40, autoimmune disease (such as lupus), existing high blood pressure, or preeclampsia in a prior pregnancy.
• Excess bleeding after birth (postpartum hemorrhage). While certain factors put people at higher risk, hemorrhage may occur with any birth, even those that follow uncomplicated pregnancies.

Most often, pregnancy can be safely navigated even when a person has health conditions. Yet having an existing condition like heart disease or diabetes does raise risk for complications and death. Now that pregnancies at later ages are more common, existing heart disease is complicating more pregnancies. Once rarely needed, large multidisciplinary teams of health professionals are now often required to care for pregnant people with complex cardiac needs or other health conditions.

Many pregnancies are unintended

Nearly half of all pregnancies in the United States are unintended. In some cases that means a pregnancy is wanted at a future time; in others that a pregnancy is not desired.

Why do so many unintended pregnancies occur? Nine in 10 sexually active women who are not trying to get pregnant report using some form of birth control. Of course, not all types of birth control are highly effective. In a year of use, 13 out of 100 people relying on condoms alone — and up to 23 out of 100 relying on fertility awareness methods — will become pregnant.

Unintended pregnancies occur even when people use very effective contraceptives. With perfect use (which is very hard to achieve), fewer than one in 100 women taking birth control pills for a year will become pregnant. With typical use, seven in 100 will become pregnant. More than 13 million US women use surgical sterilization, such as tubal ligation, as a permanent form of birth control. Given the failure rate of nearly one in 100, research suggests more than more than 65,000 unintended pregnancies may occur annually after these procedures.

Health factors in, too. Certain medical conditions or medications, such as medicines used to treat epilepsy, may also increase the risk of contraceptive failure. Health conditions also dictate whether people can use some of the more effective forms of birth control.

A narrowing of health care choices and life choices

Pregnancy, childbirth, and parenting alter the trajectory of many lives — parents, siblings, and wider family — even when people choose this path. Since June 2022, when the Dobbs Supreme Court decision overturned a national constitutional right to abortion, at least 14 states have banned or severely restricted the ability to make choices once pregnant. Even before Dobbs, nearly 10% of people seeking abortion care in the US had to travel out of state.

Research shows that women who seek an abortion but are denied abortion care are more likely to have health problems during their pregnancy and to experience financial difficulties or live in poverty years later. State bans on abortion care will have a disproportionate impact on Black and low-income women, who already are at higher risk for complications or death related to childbirth. Ultimately, legislation that restricts or bans comprehensive health care that includes abortion care puts all people capable of pregnancy at risk — medically, economically, and socially.

Like pregnancy itself, the decision to remain pregnant is deeply personal. And as with all health care, patients and physicians should be able to freely consider all medical options to help guide decisions, including ending a pregnancy. Although abortion care is more restricted today than it has been since 1973, options are available and remain a critical part of maternal health care.

Selected resource

Contraceptive Technology, 21st edition, Managing Contraception LLC. More information is available on the Managing Contraception website.

About the Authors

Sara Neill, MD, MPH,

Contributor

Dr. Sara Neill is a physician-researcher in the department of obstetrics & gynecology at Beth Israel Deaconess Medical Center and Harvard Medical School. She completed a fellowship in complex family planning at Brigham and Women's Hospital, and … See Full Bio View all posts by Sara Neill, MD, MPH

Scott Shainker, DO, MS, Contributor

Scott Shainker, D.O, M.S., is a maternal-fetal medicine specialist in the Department of Obstetrics and Gynecology at Beth Israel Deaconess Medical Center (BIDMC). He is also a member of the faculty in the Department of Obstetrics, … See Full Bio View all posts by Scott Shainker, DO, MS

Are you having a little trouble hearing conversations? If so, you’re not alone. An estimated 23% of Americans ages 12 and older have hearing loss. Although most of those people have mild hearing loss, for people ages 80 years and older, it’s more common for hearing loss to be moderate to severe than mild.

But not only is moderate to severe hearing loss disruptive to one’s life, it also makes you more likely to develop dementia. A new study helps explain why — and what you can do about it.

What did the new study look at and find?

A study published in JAMA focused on a sample of adults in the United States from the National Health and Aging Trends Study, which follows Medicare beneficiaries. The participants sampled were 70 or older.

The researchers found that about 33% of participants had normal hearing, 37% had mild hearing loss, and 30% had moderate to severe hearing loss. Dementia occurred least often among those with normal hearing (6%), more often among those with mild hearing loss (9%), and most often among those with moderate to severe hearing loss (17%). That’s a large increase in risk, particularly for those whose hearing loss is moderate to severe.

What else to know about this study

The study sample was selected to make it possible to analyze subgroups by age and apply findings to a diverse population. The sample included additional participants ages 90 years and older, and additional participants who identified as Black. Of the 2,413 total participants, 53% were ages 80 years and older, 56% were female, 19% were non-Hispanic Black, 4.5% were Hispanic, and 74% were non-Hispanic white.

Also, unlike previous research, this study looked objectively at hearing loss and dementia. Prior research had shown that hearing loss is thought to account for about 8% of all dementia cases worldwide. Exactly why the connection exists is not known.

It’s important to note that most large studies that found this link were based on questionnaires that people fill out. In other words, no one actually measured the hearing of those participating in the study to make sure that they had hearing loss — or that their hearing was really normal.

In this new study, however, the investigative team used an electronic tablet-based audiometer to evaluate participants’ hearing for four pure tone frequencies that are most important for understanding speech. So, for the first time in a large study, there was objective measurement of hearing loss.

How do hearing aids reduce the risk of dementia?

If you have hearing loss, does that mean you’re doomed to develop dementia? Not at all. This study found that those with moderate to severe hearing loss could significantly reduce their risk of dementia simply by using hearing aids.

This research helps us understand why hearing loss causes dementia. Here’s the connection:

There is increasing evidence that the more the brain is stimulated, the less likely it is that dementia will develop. When there is hearing loss, auditory stimulation is reduced. This, by itself, likely increases dementia risk. But even more important is that when an individual suffers from moderate to severe hearing loss, they are less likely to participate in social activities. Perhaps they are embarrassed about their hearing loss. Or they may simply find it unrewarding to attend a social event when they cannot hear what is going on.

It turns out that social activities are one of the best ways to stimulate the brain, as there is evidence that our brains evolved to facilitate social behavior. Given all this information, you won’t be surprised to learn that reduced social activity has been linked to cognitive decline. Thus, this new study provides additional evidence that the reason hearing loss increases the risk of dementia is because hearing loss reduces brain stimulation — both directly and through reduced social interaction.

What to do if you have hearing loss

Don’t let hearing loss raise your risk of dementia.

• Keep your ears clean. (But remember, never put anything in your ears smaller than your elbow. Ask your doctor if you’re not sure how to clean your ears.)
• If you can’t hear and you don’t have hearing aids, get them. Hearing aids now available over the counter can help many people with mild to moderate hearing loss.
• If you have hearing aids, wear them.
• If your hearing aids aren’t working, get them fixed.
• Don’t be passive — ramp up your social life and other activities.

All these things will help to reduce your risk of dementia. And you might just find that, despite some hearing loss, you’re enjoying life more.

About the Author

Andrew E. Budson, MD,

Contributor; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Andrew E. Budson is chief of cognitive & behavioral neurology at the Veterans Affairs Boston Healthcare System, lecturer in neurology at Harvard Medical School, and chair of the Science of Learning Innovation Group at the … See Full Bio View all posts by Andrew E. Budson, MD

It used to be that doctors would automatically recommend treating all men with prostate cancer, even if their initial biopsies suggested the disease would grow slowly (or at all). But during the last several decades, the pendulum on treatment has swung the other way.

Doctors are now likely to advise active surveillance for low- to intermediate-risk cancers that may never turn deadly over the course of a man’s life. Active surveillance involves routine PSA checks, follow-up biopsies, and more recently, magnetic resonance imaging of a patient’s tumor. Treatment is initiated only when — or if — the disease shows signs of progression.

Recent evidence from Johns Hopkins University shows that the long-term risks of metastasis and death from low-grade prostate cancer among men on active surveillance averages just 0.1%. But doctors who care for such men also face a nagging question: which of their patients might have more aggressive cancer that should require closer monitoring? New findings published by the Johns Hopkins team in January provide useful insights.

The researchers’ approach

The researchers in this case zeroed in on the prognostic value of so-called perineural invasion, or PNI, on tumor biopsy samples. PNI simply means that cancer cells are moving into the perineural space between nerves in the prostate and their surrounding tissues. A finding of PNI raises red flags because the perineural space “provides a conduit by which tumor cells can potentially escape the prostate and grow elsewhere in the body,” says Dr. Christian Pavlovich, a urologic oncologist at Johns Hopkins who led the research.

Dr. Pavlovich’s team wanted to know if PNI detected on initial or follow-up biopsies would be associated with higher risks for cancer progression. So they analyzed long-term follow-up data from 1,969 men who had enrolled in an active surveillance research protocol at Johns Hopkins between 1995 and 2021. All the men were diagnosed initially with Grade Group 1 prostate cancer (the least risky form of the disease) and had undergone at least one follow-up biopsy since then.

What did the results show?

Among the 198 men with PNI, 44% of them (87 men in all) eventually progressed to Grade Group 2 prostate cancer, which is a more advanced form of the disease with an intermediate risk of further spread. Conversely, just 26% of the remaining 1,771 men without PNI (461 men) had progressed to Grade Group 2.

Pavlovich emphasizes that despite the new findings, PNI “does not make patients ineligible for active surveillance.” Importantly, the research showed that PNI was not associated with high-risk features, such as cancer in the lymph nodes of patients who wound up having surgery, or post-surgical elevations in PSA that show cancer still lurks in the body.

“What we’ve really shown here is that PNI puts men at a slightly higher risk of extraprostatic extension (cancer cells located just beyond the confines of the prostate),” Pavlovich says. “This is not necessarily a new finding. But PNI only occurs in about 10% of Grade Group 1 patients, and this is the boldest statement yet from the largest study conducted so far.” Pavlovich and his colleagues concluded that PNI provides an inexpensive and readily available indicator for identifying which men on active surveillance will benefit from more intensive monitoring protocols, including MRI and genetic tests.

Dr. Marc B. Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, agrees, while pointing out that PNI evaluations aren’t performed often enough. A PNI analysis of pathology specimens, he says, “along with emerging and sophisticated genetic testing of the tissue samples, may lead to more certainty in our recommendations to patients.”

About the Author

Charlie Schmidt, Editor, Harvard Medical School Annual Report on Prostate Diseases

Charlie Schmidt is an award-winning freelance science writer based in Portland, Maine. In addition to writing for Harvard Health Publishing, Charlie has written for Science magazine, the Journal of the National Cancer Institute, Environmental Health Perspectives, … See Full Bio View all posts by Charlie Schmidt

About the Reviewer

Marc B. Garnick, MD, Editor in Chief, Harvard Medical School Annual Report on Prostate Diseases; Editorial Advisory Board Member, Harvard Health Publishing

Dr. Marc B. Garnick is an internationally renowned expert in medical oncology and urologic cancer. A clinical professor of medicine at Harvard Medical School, he also maintains an active clinical practice at Beth Israel Deaconess Medical … See Full Bio View all posts by Marc B. Garnick, MD