The headlines surrounding a new class of weight-loss drugs fluctuate like a patient stepping on and off a scale.
The medications, based on the drug semaglutide, are celebrated as a miracle cure for obesity one day. On another, fears of serious complications arise.
But back on the positive side: Drugmaker Novo Nordisk announced Tuesday that its version of the drug, Wegovy, also cuts by 20% the risk of cardiovascular problems such as heart attack and stroke.
While more details of the study are yet to be revealed, a University of Virginia cardiologist explained why the benefits of semaglutide-based drugs appear to outweigh the potential downsides for most patients.
The pros of Wegovy and similar drugs
Dr. David Guarraia, who recently joined UVA Health, said semaglutide, which can be found in formulations under the brand names Ozempic, Wegovy and Rybelsus, imitates a hormone released into the gastrointestinal tract while a person eats.
(Of these brands, only Wegovy has been officially approved by the FDA for weight loss.)
The drug, in a class called GLP-1 agonists, directly slows digestion in the stomach. It also communicates with the appetite centers in the brain, reducing hunger. The method of delivery is either pill or injection.
“The medication works similarly to the body’s natural hormone, but has an enhanced effect because it lasts longer in the bloodstream,” Guarraia said.
“Several trials are ongoing and will be released soon, but there has been a clear reduction in cardiovascular morbidity and mortality by treatment with GLP-1 agonists.”
He said patients as a group are seeing fewer heart attacks, strokes and cardiovascular deaths within a year to 15 months of use.
“There is a reduction in the need for reopening heart arteries,” he said. “It’s hypothesized that the impact on blood pressure, blood sugar and cholesterol may account for some of this effect.
However, there is likely a less-well-understood and perhaps more important role of GLP-1’s in reducing systemic inflammation and blood clots.”
Recent concerns about the drugs
Generally speaking, the drugs are well-tolerated, Guarraia said. Because they slow digestion, common side effects may include nausea and vomiting.
“Eating smaller meals and starting at a low dose, then increasing it slowly, often helps,” the doctor said.
But what of the uncommon side effects—in particular, recent reports of stomach paralysis in some patients?
“Severely delayed gastric emptying—called gastroparesis—appears to be a rare but possible complication, with several reported events on the FDA’s publicly accessible adverse events tracking system,” Guarraia said.
“Typically, though, severely delayed gastric emptying resolves once the medication is discontinued.”
He said the slower emptying, in fact, may be part of the reason the drugs work so well for weight loss.
To complicate matters, because drugs in the class increase insulin production and reduce sugar production in the liver, they are also used to treat patients with Type 2 diabetes—yet these patients are at risk for developing gastroparesis regardless.
“If a patient has gastric emptying issues at baseline, use of GLP-1 receptor agonists may not be appropriate,” the doctor stressed.
Another infrequent concern includes inflammation of the pancreas, he said. The drug is not recommended for patients with a family history of a rare type of endocrine cancers.
Weighing your decision
Guarraia said for patients with obesity and at high risk of cardiovascular disease, or who have cardiovascular disease with or without diabetes, the GLP-1 medications can be considered.
“We predominantly assess patient candidacy for this medication based on blood sugar and body weight,” he said. “Hopefully, insurance companies start to cover more patients who meet appropriate use criteria for the medication.”
He added that there’s no such thing as a magic pill. Drugs can help on several fronts, but good diet, exercise and lifestyle modification are essential for maintaining long-term health.
“Medications can be useful, when needed, to help improve quality of life, but only for the shortest period of time, at the lowest possible dose, to help reduce the risks for side effects and costs,” he said.
Written by Eric Williamson.
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