Type 2 diabetes: New obesity drug may halve risk, aid weight loss

• New research demonstrates that the diabetes drug semaglutide is also effective for weight loss and may help prevent people from developing type 2 diabetes.
• When some research participants were switched to placebo during the trial, their weight increased, and so did their diabetes risk.
• Researchers assessed the participants’ risk of getting diabetes in the future using a tool that can predict 10-year health outcomes.

Semaglutide is a polypeptide that physicians prescribe for the treatment of type 2 diabetes. The FDA has approved the use of Novo Nordisk’s Ozempic and Rybelsus as a once-weekly injection or as a tablet, respectively. A once-weekly injection of semaglutide with the brand name Wegovy has more recently been approved as a weight loss treatment.

A new 68-week study modeling future outcomes finds that semaglutide can reduce the risk of developing type 2 diabetes for people with overweight or obesity. The study underscores the tight link between obesity and type 2 diabetes.

A weekly dose of 2.4 milligrams (mg) of semaglutide lowered the 10-year risk of developing type 2 diabetes by about 60%, from 18.2% to 7.1%.

Although people with prediabetes were at greater risk initially, semaglutide reduced their risk by a similar amount to those with healthy blood sugar levels.

The research is being presented this month at the annual meeting of the European Association for the Study of Diabetes taking place in Stockholm, Sweden.

Body weight and the risk of diabetes increased for participants who were switched to a placebo after 20 weeks, suggesting that sustaining a reduction in diabetes risk requires continued semaglutide treatment.

Cardiometabolic disease staging (CMDS), which the researchers describe as a “validated staging tool” to assess the 10-year risk of type 2 diabetes, modeled participants’ future health outcomes. The tool can also predict the risk of cardiovascular disease.

Fighting diabetes by fighting obesity

Study author Dr. W. Timothy Garvey, senior scientist at the University of Alabama at Birmingham Nutrition Obesity Research Center, told Medical News Today:

“I’ve been making the case for some time that weight loss should be a primary therapeutic modality in type 2 diabetes as a first-line therapy, not only to control the hemoglobin A1C, and the blood sugars, but to prevent and treat all of the other complications patients with overweight or obesity have.”

“You know [people with obesity] have high rates of obstructive sleep apnea,” explained Dr. Garvey. “Obesity worsens the dyslipidemia, hypertension, [and] the glucose control, increases cardiovascular risk factors, increases the fat content in the liver and nonalcoholic fatty liver disease.”

“So weight loss will address all of those issues, whereas diabetes medicines alone, many of them won’t get that job done,” he noted.

Dr. Samuel Klein, professor of cell biology and physiology at the Washington University School of Medicine in St. Louis, who was not involved in the research, agreed with Dr. Garvey.

He told MNT that “[t]he real primary treatment for type 2 diabetes is really to reduce body weight in people who [have obesity]. And this analysis suggested that’s the case, that if you reduce body weight with newer medications that you can reduce the risk of developing type 2 diabetes.”

How semaglutide works

“Semaglutide is a GLP-1 receptor agonist and increases insulin secretion in response to a rise in glucose,” said Dr. Garvey. “But at the higher dose range, it also enters the brain and acts on satiety centers in the brain and suppresses appetite to cause weight loss.”

“It has those dual actions so, in essence, it’s kind of closed the loop now. Here we are, using a weight-loss medication to treat the diabetes, particularly when we use the higher doses of semaglutide,” he explained.

People who already have diabetes can also improve their health by losing weight.

In terms of safety, Dr. Garvey said:

“When you’re escalating the dosage, you start low and build up to mainly mitigate the nausea and gastrointestinal symptoms: nausea, vomiting, diarrhea. That occurs in about 40% of patients. It’s usually self-limited, it gets better over time, and you can continue the medicine.”

He noted, however, that semaglutide can increase the chance of gallbladder disease, so it should not be prescribed for a person “with active gallbladder disease symptoms passing gallstones, having cholecystitis, any kind of gallbladder problem.”

A possible connection to pancreatitis, he suggested, may be an additional product of gallbladder issues.

Finally, Dr. Garvey added it cannot be used with people who have “nodular thyroid cancer, because of what we’ve seen in rats. It’s not shown to be a risk in humans.”

Dr. Klein agreed, noting it is likely safe because “this is a naturally occurring compound. It says it already exists in your body.”

“I think we don’t have long-term data,” he nevertheless cautioned, “and that would need to be monitored carefully. But I don’t think you should wait for those data to come back to prevent prescribing it because it would be 10 years before you can get all that data.”

Who should take semaglutide?

While the value of semaglutide for an individual is a judgment call only their physician can make, Dr. Klein suggested: “If you want to reduce the risk of diabetes, it should be limited to those with prediabetes because those are the people at high risk.”

Dr. Klein described such people as having “evidence of abnormal blood lipids, blood pressure, abnormal glucose tolerance tests, for example, or a little bit high fasting glucose.”

Dr. Garvey made the case for prescribing semaglutide to individuals who are obese but do not show signs of being at risk for diabetes.

“I kind of speak about the complications [of obesity] in two ways. One is cardiometabolic. The other one is biomechanical. Complications are due to carrying around a heavy body mass over a longer period of time, like sleep apnea, like osteoarthritis, gastroesophageal reflux, urinary incontinence, immobility, issues that kind of deal with quality of life,” he said.

Dr. Garvey said “[a]ll of those are reasons to treat someone as well.”

Weighing the cost and benefits

Semaglutide’s pricing may be an issue for some patients, and it is not clear the extent to which employers or insurance companies will embrace funding its use.

Dr. Garvey noted: “Obesity affects one-third of Americans. And if you include overweight, it’s two-thirds of Americans. You can’t take a medication like semaglutide and treat two-thirds of our society.”

The latest data from the National Health and Nutrition Examination Survey (NHANES) for the years 2017–2018 shows that 42.4% of Americans have obesity, and this percentage surpasses 70% if it includes people with overweight.

Still, he said, “we’re paying for the complications of obesity now. So, there’s health economic analysis you could do to say, ‘well, is it cheaper to treat the disease and prevent the complications?’”

This is the reason behind the development of CMDS, “to kind of help payers and providers, and healthcare systems, to be more comfortable with the rational use of the medication,” Dr. Garvey explained.

The obesity bias

Dr. Garvey also said a reluctance to pay for obesity treatment “reflects a bias against obesity. You know, a lot of healthcare professionals even, like, in lay society, think that obesity is a lifestyle choice and not a disease.”

Dr. Klein said that it was becoming more “abnormal” to see lean North Americans, and “normal to be overweight and obese.”

“You know, the buck does stop with the person eating the food, but it’s difficult to do that,” admitted Dr. Klein.

“This is due to this interaction between our genes that drive us to like food, want food, eat food, as well as want to not become a very low body weight to die from starvation, all mixed together with our environment.” Dr. Klein cited “all these factors around us 24/7 that are driving you to eat more calories than you burn up.”

“Take someone who’s skinny, who’s lean,” said Dr. Klein, “and ask them to cut their calories in half, which is what we do to [people with obesity], and see how long they can last doing that.”

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