Semaglutide for obesity: Scientist deems short-term solution as weight loss doesn’t stick

10 Mar 2023 --- As prescription weight loss drugs become more available in different countries around the globe, there have been mixed reactions to using semaglutide to tackle obesity. While the innovation may help those struggling with obesity, the question of safety and skepticism about it being a long-term solution remains, as 90% of people gain back the weight lost after finishing the treatment.

Wegovy, a brand name for semaglutide manufactured by the Danish pharmaceutical company Novo Nordisk will shortly launch in the UK and expand to a larger European market. The National Institute for Health and Care Excellence has published guidelines on the drug.

NutritionInsight speaks with Alex Miras, a professor of endocrinology at Ulster University, Northern Ireland, about the medication. He dives deeper into how the drug affects the human body, nutritional guidelines and benefits of the obesity medication for public health while pointing out its limitations.

“When the patients are put on medication, it has shown to be beneficial for their health. The problem is that the treatment is stopped after two years because it is no longer cost-effective beyond two years. This makes sense regarding cost, but it doesn’t make clinical sense, as we wouldn’t do the same for any other chronic conditions we are treating.”

“All studies have shown that the patients’ cardiometabolic benefits from the drug almost completely disappear when the medication is stopped. So I don’t think that it’s the best way forward. It just demonstrates that it’s a good but not yet perfect process,” Miras adds.

When off the drug
The medication is a hormone working in the brain’s appetite center. The medicine addresses the biological mechanism and makes people feel less hungry. 

“When you remove the drug, all of the biological signals to the brain from the medication completely disappear,” says Miras. He further details that the average weight loss is 15%, which is “very substantial from a clinical perspective.”

Although, he stresses that 90% of people will not be able to keep off the weight when you remove the treatment. “If we look at this overall, it’s a very positive guidance. It will help a lot of people, but it has its limitations.”

Miras says that 100 years ago, the environmental factor wasn’t a problem, as food items were not as widely available and cheap as today.Diets vs. genetics
Miras explains that when it comes to body weight, 70% is determined by genetics and 30% by the environment.

“So, a large proportion is determined by factors outside our control.”

He says that one hundred years ago, the environmental factor wasn’t a problem, as food items were not as widely available and cheap as they are today. With advances in civilization, including the modern food industry, the combination of energy-dense, easily accessible and affordable food and faulty biology is a significant issue.

“It’s the combination that has led us to our current problem, so without a doubt, we must optimize the environment, regulate the food industry and promote public health and nutrition. But we must also treat the people not responding to the preventative measures.”

“The people that receive the drug are those that have not responded to what we are currently doing to prevent obesity. Therefore we are obliged to treat them, as they are presenting a disease to us,” Miras adds. 

“You can always try different lifestyle modification measures, which include nutritional therapies and physical activity.”

The World Obesity Federation recently announced that it forecasts a quarter of the population to be obese by 2035.

Differences in efficiency
The efficacy of solely lifestyle modification is small, less than 5%, says Miras. 

What the medication does is enhance the weight loss achieved through lifestyle modification. Therefore, they should be used in combination.

He further details that the medication changes how people eat by increasing fullness and reducing hunger, making people eat smaller portions. 

“It makes a lot of sense to suggest to the patient that in addition to eating less, they should also eat healthy at the same time, such as avoiding energy-dense food. Reducing calorie intake and changing food choices will have the most significant impact,” Miras stresses.People who take weight loss medication with semaglutide report that fatty and sweet foods can make them sicker, compared to previously.

“However, there is no interaction between nutritional consumption and the drug, so if someone follows a specific diet, it won’t interfere with the drug. However, users report that fatty and sweet foods can make them a bit sicker compared to previously, and so they avoid it.”

Miras highlights that in terms of nutritional deficiencies, no major micronutrient deficiencies have been seen among the patients. However, for those losing a substantial amount of weight, muscle loss can be an issue. 

“We should strive to preserve as much muscle as possible because it’s beneficial in many ways. Therefore high-protein diets are certainly useful and recommended after any weight loss intervention.”

Blocking intestines?
Meanwhile, a recent China-based study claims that the drug might have severe adverse effects, as it found that it puts users at risk of enlarging or blocking intestines, which might be fatal. However, the experiment was conducted on rats, so conclusions on how it impacts the human gut are unknown.

The study, published in Acta Pharmaceutica Sinica B, demonstrates the adverse effects of glucagon-like peptide-1 (GLP-1) receptor – an intestine-derived hormone commonly used to treat Type 2 diabetes, hypertension, dyslipidemia and obesity, one of those is semaglutide.

“While their efficacies and safety profiles are widely accepted, long-term adverse events such as the increased risk of intestinal obstruction have been reported in diabetic patients, which is 4.5 times higher than those receiving other glucose control medications,” the study notes.

It continues by referring to another study, “a real-world study of 25,617 subjects demonstrated a 3.5-fold increase in the intestinal obstruction rate associated with GLP-1RA (GLP-1 receptor agonist) treatment.” 

“During the two years, the drug is cost-effective, but beyond the two years, it’s not, although still clinically effective,” says Miras.Yet, the authors say that the risk of chronic intestinal obstruction in humans cumulates over time, with a high occurrence of appearing 1.6 years following a GLP-IRA treatment. 

“However, clinical trials on GLP-1RAs usually do not last for more than a year and relevant studies revealed that the incidence of constipation is independent of short-term doses of GLP-1RAs,” they underscore.

Miras comments that among many high-quality studies conducted on humans, none shows a potential signal for death, intestinal obstruction or any longer-term adverse effects.

“The worst case scenario with semaglutide is that people can, rarely so, develop pancreatitis, which is reversible. When the medication is stopped, the pancreas returns to normal. Not commonly, people can develop gallstones, which in most cases are mild or moderate, but we don’t have any other signal for any other serious adverse events.”

Cost-effectiveness
To fight child obesity, the American Academy of Pediatrics recently published a report supporting weight loss drugs or surgery as an additional measure to nutritional diets and exercise. 

“During the two years, the drug is cost-effective, but beyond the two years, it’s not, although it is still clinically effective,” Miras notes.

When asked if a short-term solution really is considered cost-effective, Miras responds that it’s a limitation in the guidelines that it’s only used for two years.

“We can only treat this disease in primary care as we cannot treat it in secondary care. We need funding to get staff to deliver the treatment in primary care, which will also be more cost-effective as secondary care is more expensive.”

By Beatrice Wihlander