The science and side effects behind the semaglutide weight loss drugs
How do these drugs work?
Drugs such as semaglutide mimic the actions of a hormone called glucagon-like peptide-1, or GLP-1. These so-called GLP-1 analogues have several effects, including slowing stomach emptying, acting on the brain to reduce appetite and boosting the release of insulin, which helps to regulate blood sugar levels.
For more than a decade, GLP-1 analogues have been used to help people with type 2 diabetes control their blood sugar and some users experienced modest weight loss. “These drugs augment a system that already exists within the human body, whose role it is to suppress appetite following meal ingestion,” says Simon Cork at Imperial College London.
Why are they making headlines now?
GLP-1 analogues have started to be prescribed for weight loss in people without type 2 diabetes. They have also become available in formulations that are more potent and easier to use.
Initially GLP-1 analogues were approved for use at a lower dose and needed to be given by twice-daily injections. In the latest formulations they are once-weekly injections, with Wegovy’s full dose being 2.4 milligrams for weight loss and Ozempic being used at a maximum dose of 2 milligrams for type 2 diabetes.
How widely available are they?
In 2021, Wegovy was approved for weight loss in several countries, including the US and Canada. Praise from some celebrity users brought it widespread publicity.
Manufacturing problems meant its manufacturer, Novo Nordisk, had trouble meeting global demand, so some doctors started prescribing Ozempic, which had been approved for people with type 2 diabetes in certain countries several years earlier. This led to shortages for people who required it for diabetes control.
In the UK, Wegovy was approved in 2021, but only got the nod from England’s medical guidelines body the National Institute for Health and Care Excellence in March 2023, when it said the drug should be given by weight loss clinics within the country’s national health service. Wegovy is expected to become available in the UK this year, while Ozempic has been available for type 2 diabetes since 2019.
In June 2023, the UK government announced the introduction of a two-year pilot that gives people with obesity access to new drugs, such as Wegovy, outside of a hospital setting.
How effective are they?
Very. It is a cliche but obesity doctors are talking about a paradigm shift in the field of obesity management. Previously, a loss of about 5 per cent of body weight might be considered a good result for any weight loss intervention outside of stomach surgery and is considered a benchmark in obesity drug trials.
In fact, some people seem to feel that the GLP-1 analogues have caused them to become too gaunt, as reflected in the rise of the search terms “Ozempic face” and “Ozempic butt”. “Ozempic doesn’t do anything specific to the skin,” says Alexander Miras at Ulster University, UK. It is the weight loss that causes these apparent side effects, with similar outcomes often also occurring after weight loss surgery, he says.
Do the drugs have any side effects?
Side effects can be mild, such as nausea, constipation and diarrhoea, which tend to occur as people get used to the drug. More worrying side effects include inflammation of the pancreas, although this is relatively rare.
How about hair loss?
Hair loss has been reported by some semaglutide users. This is also sometimes seen after significant weight loss from other causes, such as stomach surgery, says Miras.
Hair loss following weight loss surgery is thought to be due to physiological stress on the body causing an increased number of hair follicles to enter their “resting” phase, which leads to the hairs falling out a few months later. It stops when the weight loss stabilises, however, the hair doesn’t always grow back, says Miras.
Do these drugs cause suicidal thoughts?
GLP-1 analogues – such as Ozempic and Wegovy – are being investigated by the European Medicines Agency (EMA) after recent reports that they may cause thoughts of suicide or self-harm. This was after Iceland’s health regulator received three such reports regarding semaglutide and another drug called liraglutide, which is an earlier GLP-1 analogue.
The EMA says it is analysing about 150 reports of possible cases of self-injury and suicidal thoughts. This doesn’t mean the medicines caused these effects, however, only that people reported these experiences after starting to take them. “More work is needed to determine if a causal link exists,” says Michael Schwartz at the University of Washington in Seattle.
A spokesperson at Novo Nordisk, the manufacturer of liraglutide and the semaglutide drugs Ozempic and Wegovy, told New Scientist: “GLP-1 receptor agonists have been used to treat type 2 diabetes for more than 15 years and for treatment of obesity for eight years. The safety data collected from large clinical trial programmes and post marketing surveillance have not demonstrated a causal association between semaglutide or liraglutide and suicidal and self-harming thoughts.”
Do these drugs help with addictions?
Perhaps. There have been several anecdotal reports of people taking these medicines for diabetes or weight control who lose their urge to drink alcohol or see waning of other habits that can be described as “behavioural addictions”, such as compulsive shopping.
This is supported by research in animals that found the GLP-1 analogues lower consumption of alcohol and addictive drugs. A small trial in people has hinted at a similar effect from a GLP-1 analogue called exenatide, which reduced heavy drinking, but only in people who were obese.
The explanation can be connected with the way the drugs act on the brain to reduce food cravings, but the exact mechanism is unclear. We are only at the beginning of understanding how these treatments can support people with alcohol and drug additions, says Daniel Drucker at Sinai Health in Toronto, Canada. “The clinical trial data is not yet in to substantiate the anecdotes.”
What happens to a user’s weight long-term?
The longest trial of Wegovy lasted two years and found that people’s weight broadly plateaued in the second year.
In most countries, Wegovy has been approved for two years’ use, but if people stop taking the drug, they generally regain the lost weight – two-thirds of it after one year, according to one trial.
“The weight loss is only sustained for as long as the drug is taken because as soon as you stop the drug, all of those physiological processes that are trying to get your body weight back up kick in again,” says Cork.
This suggests that after two years of use, there will be demand from consumers for doctors to continue prescribing the drug “off label”. “I think there’ll be a big push to try to change those guidelines,” says Cork.
Ozempic can be prescribed long-term for type 2 diabetes because the condition is usually life-long.
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