We talked to Salvatore Maria Corsello, Professor of Endocrinology at UniCamillus University
We are in swimsuit season, and losing weight is an imperative in western society. Losing weight is a need that should be dictated by reasons of good health; however, more and more often it is linked to aesthetic connotations. Thus, we end up adapting to our image-driven society and exaggerating the concept of thinness, with all the physical and psychological consequences that this entails.
Losing weight inevitably implies some sacrifices, i.e. a lifestyle change, becoming more active and more careful with our diet. These changes guarantee excellent results in the long term, but may still involve some deprivation, such as reducing any overindulgence and dedicating ourselves to some sport.
Precisely for this reason, the attempt to look for shortcuts is always a great temptation. This is demonstrated by the various products passed off as slimming, such as miracle teas, vibration platforms, fat-melting bands, and other absurd extravagances that are not supported by the slightest scientific merit. Yet there are buyers, and there are many: whether they are naive or ill-informed, the least one risks is being fooled, especially when it comes to remedies that do not work. If they do work, though, the harm could be to upset the balance of the organism. This happens when one turns to drugs in order to lose weight. Drugs that are generally used for something completely different!
A few examples? Thyroid drugs, which increase metabolism but can also cause heart failure; diuretics, intended for hypertensive and cardiac individuals but also used to lose weight, resulting in electrolyte imbalances and kidney damage; but also laxatives, amphetamines, and many others that are extremely harmful if not prescribed by a doctor.
Just recently, the European Medicines Agency (EMA) raised the alarm about another type of drugs used off-label to lose weight by non-obese people: diabetic drugs. This has led to a shortage of Glucagon-like Peptide-1 (GLP-1) agonist drugs on the market, such as Ozempic (semaglutide), Saxenda (liraglutide), Trulicity (dulaglutide) and Victoza (liraglutide). The lack of such drugs, in turn, has serious consequences for those who really need them and find themselves unable to use them, i.e. diabetics.
Another risk of growing demand is the introduction of counterfeit and falsified products onto the illegal market: these non-compliant products may not be manufactured to safety and quality standards, posing a serious risk to public health.
The reckless off-label use of these anti-diabetic active ingredients has unfortunately also been encouraged by their insane advertising by celebrities such as Elon Musk, but also by the so-called ‘pharma influencers’ on social networks for teenagers, such as TikTok.
To find out more, we talked to Salvatore Maria Corsello, Professor of Endocrinology at UniCamillus University.
What is the mechanism by which an anti-diabetic drug can make you lose weight?
“Anti-diabetic drugs which, in addition to their blood glucose-lowering action, have also shown an effect on weight loss are GLP1-RA (glucagon-like peptide 1 receptor agonists) and, to a lesser extent, SGLT2i (sodium/glucose cotransporter 2 inhibitors).
Specifically, GLP1-RA has a dual action: peripheral and central. The first is expressed by slowing down intestinal transit and gastric emptying, thus giving a feeling of abdominal ‘fullness’; the second acts on the satiety centres and ‘rewarding’ circuits, i.e. the brain’s reward and gratification systems.
Both mechanisms induce an increased sense of satiety, leading to a reduction in calorie intake and cravings for foods high in fat and sugar. This leads to significant weight loss, which, with the new drugs recently on the market, can be as much as 20% of body weight in obese individuals.
The best known drug in this class of molecules is semaglutide (Ozempic, marketed as an antidiabetic, and Wegovy, the same as Ozempic but at a higher dosage, recently introduced as an anti-obesity drug).
In the same category are liraglutide, dulaglutide, lixisenatide, exenatide and tirzepatide.
They are all used in weekly subcutaneous injections. Semaglutide is also available orally (Rybelsus, marketed as an oral antidiabetic).
As for SGLT2i (glyfozines), their action on weight loss (less significant) comes from increased urinary excretion of glucose and consequent loss of calories through urine.
Finally, it should be emphasised that the most widely used of the oral hypoglycaemic drugs, metformin, has a significant effect on weight reduction and body composition through insulin sensitisation but also through different molecular mechanisms that are being studied.”
What are the risks associated with the misuse of antidiabetic drugs by people trying to lose weight without having diabetes?
“These molecules originated as drugs for the treatment of diabetes but, given their efficacy in weight reduction, they have also been given an appropriate indication for the treatment of obesity. The indication is limited to subjects with a body mass index greater than or equal to 30 (or 27 in the presence of significant internal comorbidities). Body mass index (BMI) is obtained by dividing the weight expressed in kg with the height expressed in metres squared.
Unfortunately, the message has gone out that these drugs are a ‘shortcut’ to losing weight even in individuals who do not belong to the categories listed above. Efficacy in inappropriate cases is extremely limited, and therefore the balance between risks and benefits is very disadvantageous: in fact, these drugs can give certain complications, albeit not very frequent, such as gastrointestinal disorders (nausea, vomiting, constipation or diarrhoea) up to acute pancreatitis. They should therefore only be used when strictly necessary.”
What are the safe and effective weight loss alternatives that you can recommend to those seeking to lose weight in a healthy way?
“The only way to lose weight in a healthy way is to have a healthy lifestyle: always eating little and well and exercising regularly. The best diet to follow is none other than the Mediterranean diet.”
Are there cases in which the risk of obesity is such that slimming drugs become necessary?
“There are cases of severe obesity in which lifestyle alone may not be sufficient—at least initially—to bring about adequate weight loss. There may also be particularly high-risk cases, such as patients with multiple internal medicine comorbidities, where adequate weight control needs to be achieved ‘quickly’ to reduce associated complications.
Another situation to be avoided is the ‘weight-cycling syndrome’, or ‘yo-yo dieting’, in which the patient undergoes major weight fluctuations in a short time. This phenomenon is associated with an increased cardiovascular risk because most of the fat that returns is visceral fat, with a worsening of the fat/lean mass ratio. From this point of view, it is important to inform patients about the risk of regaining much of the weight lost when stopping the treatment of slimming drugs and especially GLP1-RA. In other words, any drug therapy must always be associated with—and above all followed by—appropriate behavioural therapies with regard to appropriate lifestyles.”
Pharma influencers and various VIPs have been advertising these drugs in terms of slimming…
“Unfortunately, social networks have a very wide circulation and a great influence on the general public, which is not regulated by any adequate legislation. Sensitive and specialised topics such as health and drug therapies should only be dealt with by competent people.”