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Title : Curious about new, popular weight-loss drugs? Here's a lowdown
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Curious about new, popular weight-loss drugs? Here's a lowdown

Axios Visuals map adapted by Ky. Health News; click to enlarge

Editor's note: At the end of 2023 Kentucky led the nation in the percentage of state residents, 2.1%, who had received the new class of diabetes and weight-loss drugs.

By Katelyn Jetelina
Your Local Epidemiologist

You’ve probably heard of Ozempic by now. It is everywhere. Sales are up more than 300% and research studies are coming out like a firehose, but future population-level implications are unknown. Here, we catch you up on the science and what it may mean for you.

Ozempic (one brand name for the substance semaglutide) is one of many medications under the umbrella of “GLP-1 receptor agonists.” Others are Trulicity (dulaglutide), Wegovy (semaglutide) and Mounjaro (tirzepatide).

GLP stands for glucagon-like peptide 1. GLP-1 is a hormone produced in the intestinal system and released when you eat food. It is a natural signal saying you have eaten enough food. Naturally occurring GLP-1 comes and goes in a few minutes.

These medications mimic this natural process but for longer. Ozempic, for example, stays in our system for an entire week. It also slows down gastric emptying, thereby slowing down digestion.

How effective are these drugs? Very. The original clinical trials that supported initial FDA approval for patients with diabetes blew expectations out of the water. It improved:

• Blood sugar control (A1c reduction)
• Weight loss (average 15 pounds)
• Unexpected positives, like reduced kidney disease (24% less likely to experience kidney failure and death due to kidney complications)

Since the first clinical trials, studies have tested its use in non-diabetic individuals, and its is effective in weight loss. A meta-analysis of eight studies found a significant decrease (about 10% of body weight). None saw an increase. Also, it has protective effects on the heart, such as reduced blood pressure and triglycerides.

 
What happens if you stop taking it? Unfortunately, weight (and other outcomes) rebound. As shown below, after the original clinical trial (68 weeks), people who stopped taking it regained their weight.

The use of GLP-1’s as a motivating tool for sustained change has been less studied. Will these be lifetime drugs like other medications (e.g., statin drugs for heart disease) or a tool to titer up or down in times of need? This is a big unanswered question.

While obesity often involves an energy imbalance where calories consumed exceed those expended, it’s influenced by genetics, socioeconomic status, environmental factors, and mental health. These factors contribute to a complex web of challenges that may extend beyond individual choices alone.

What about kids? Ozempic isn’t officially approved by the FDA for children (but can be used off-label), but Wegovy is approved. In 2023 alone, about 31,000 children aged 12 to 17 and 162,000 aged 18 to 25 used these medications.

A recent meta-analysis found treatments led to modest reductions in body weight and improved glycemic control in children with insulin resistance.

Ozempic babies? The term refers to a recent phenomenon where women are reporting unplanned pregnancies. This has sparked discussions on social media and in the medical community about the potential impact of these drugs on fertility. Why could this be happening? Two hypothesized pathways:

• 1. These drugs delay gastric emptying, which can impact the effectiveness of oral birth control by slowing down the rate of absorption
• 2. Weight loss enhances fertility, making it easier for women to become pregnant. This is particularly true for women with Polycystic Ovarian Syndrome, in which weight loss is known to boost fertility significantly.

However, it’s recommended to stop the medication two months before trying to get pregnant (see more below).

 

Datawrapper graph by YLE; data from Ghusn et al., JAMA

Are there downsides to the meds?

Like any medication, there are side effects and risks, some known and some theoretical, and many with mixed study results. Individuals must weigh the risks of obesity with the small but meaningful risks of the medication.

 
Many people experience side effects, particularly nausea and diarrhea. A recent analysis from an insurance agency found that 6 in 10 people who start the drugs quit before they see benefits because of side effects. These tend to go away after a few weeks, but they can substantially impact the quality of life until then.

Muscle loss: Most (60-75%) weight loss is from fat, but some is from non-fat, including muscle. This could lead to a rare condition called sarcopenia—loss of muscle mass and strength where you can’t do much because you’re physically weak. Research is mixed, though, on how often this happens, and it may be minimal when combined with exercise and adequate protein intake.

 
Increased risk of thyroid cancer. A small French case-control study found an elevated risk of thyroid cancers (58% elevated relative risk) and medullary thyroid cancer (78% elevated relative risk) after GLP-1’s. However, another study in Scandinavia with more than 400,000 people found no risk of thyroid cancer after 3 years. Regardless, the potential increase in absolute risk is very small.

Mental health. There is a big debate on what is happening in the brain. GLP-1 is not only produced in the gut but in the brain as well. Some evidence has correlated the usage of GLP-1 medications with suicidal ideation. However, recent evaluations by regulatory agencies found no substantial evidence after extensive review. Some studies have even suggested a potential decrease in the likelihood of anxiety and depression.

Eating disorders. It is a growing concern that GLP-1s may increase the risk of disordered eating, particularly among those who are high-risk (e.g., prior history of eating disorders).

 
Pregnancy. Pre-clinical trials on rats found GLP-1s are more likely to have offspring with birth deformities, so it’s not recommended to take during pregnancy.

While these new drugs have a strong safety profile based on available data, human studies are only about 5 years old. This means the long-term effects are not yet fully understood. However, we do have data from drugs in the same class that started testing in 2006, showing a consistent safety profile. Continued monitoring and research are essential to determine whether theoretical risks are real in light of new data.

This means decisions today must be made based on what is available and in the context of individual risk factors. For example, if you have a history of eating disorders, the risks of taking the medication may outweigh the benefits.

What does the future look like? After a century of fad diets and weight loss gimmicks, people are tired: some from fighting stigma and others from trying to lose weight unsuccessfully. These medications have proven to work, and the market shows it: GLP-1 prescriptions have increased by over 300% since 2020. A recent poll indicates that nearly half of adults express interest. But there’s no sugarcoating it: It’s expensive, about $1,000 per month without insurance. The price should decrease dramatically in about 8 years once the patent expires and the generic version comes to market.

On a population level, these drugs will likely have widespread impacts, just like the iPhone, which can be good or bad, depending on who you ask. Given the massive impact obesity has had on health in the past two decades, this could be extraordinary for lifespan and quality of life. It could also have ripple effects on the fast-food industry and save millions of dollars in health care costs.

But it could further widen health disparities, given the cost, and hurt body positivity, losing much ground gained. We also cannot ignore that these drugs benefit a billion-dollar pharmaceutical industry when underlying societal causes should be addressed for prevention. And, the fact there are numerous other benefits to a healthy lifestyle.
Bottom line

GLP-1 drugs offer much-needed hope to individuals, and a flood of studies show their effectiveness. However, there are both demonstrated and theoretical risks to consider. Regardless, obesity deserves compassion, and perhaps 21st-century tools can help foster a supportive environment that promotes lasting progress.

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