The scientific community is awaiting with great interest the results of clinical trials currently underway to detect biomarkers that will predict whether a patient will respond to anti-obesity treatment, and whether their weight loss will be mainly fat or muscle. As explained by Tania Mantuvalou 104,9 MYSTICIA HEALTH”, General Practitioner, scientific associate of the Medical School of the University of Athens Evanthia Papageorgiou, a not insignificant percentage of patients, around 10-20%, show very little or even zero weight loss. The cause, she says, is multifactorial, as neurohormonal mechanisms, genetic factors, culprit genes, or even the patient’s own metabolic profile are involved. “At the moment there is no clinically established biomarker that acts prognostically. In clinical practice there is a device that measures body composition, i.e. percentage of fat, muscle mass, cell mass and water, as well as the rate of metabolism. And from there we can clinically deduce if there is insulin resistance. Two or more measurements show us whether the patient is losing muscle mass or fat, and that’s how we determine if there is a response to treatment.” In the following interview, Papageorgiou outlines the key points of current clinical practice, the most common patient errors, the differences between available drugs, and the latest clinical trials and real-world data that are shaping the future of obesity treatment.
Ερ: What is the right first step?
Ab>Ab:The right first step is to realize that one is sick, as obesity is a disease. And for this very reason, as for any disease, one needs to consult a specially trained doctor and follow his instructions. Not forgetting that in every disease, individualization in the management of the patient is required.
Ερ: What should someone considering seeking medical help know
About: Be prepared for a series of laboratory and possibly imaging tests, but also for the fact that he will need to follow a diet and exercise regimen, because a drug alone is not enough. Also, he/she should not be negative to taking medication, because this is something that we sometimes encounter in patients. Above all, he should know that the weight loss process requires consistency, patience, perseverance and long-term collaboration with the attending physician: general practitioner, or internist, or diabetologist, or endocrinologist.
Ερ: What are the most common mistakes patients make ;
Απ>Απ: Don’t follow diet and exercise, are not consistent with medical monitoring, or have no medical monitoring at all and decide on their own dosage, or change it, based solely on how much and how quickly they want to lose weight. They are even influenced by other patients’ posts on social media, who are also taking medication without medical monitoring, or even by shows that have no scientific background.
Ερ: Are all drugs on the market the same, or are there significant differences?
About:Most drugs belong to the same class, GLP1 agonists, and have the same route of administration. However, there are some differences and therefore individualization in patient management is considered necessary. For example, one of the drugs has been approved even in our country for children under 12 years of age. Some medicines also have more side effects than others. Probably, they are not tolerated by some patients. So we may be talking about a common class of drugs, but with differences between them .
Ερ: Do children take the same dose as adults and what kind of side effects do they experience?
About:Children take the same dose as adults and experience the same side effects. Officially, semaglutide has been approved by the US Food and Drug Administration (FDA), the European Medicines Agency (EMA) and the FDA for children over 12 years of age who are obese or overweight and have co-morbidities. It is important for children because it prevents, or prevents obesity in the future, as well as diabetes.
Why up to 20% of patients don’t respond to treatment – Indicators will predict whether you will lose mostly fat or muscle
Ερ: Which patients do not respond to these treatments at all and why?
About:There is a non-negligible proportion of patients, around 10-20%, who experience very little weight loss, even zero weight loss. The cause is multifactorial. Neurohormonal mechanisms are involved, for example, reduced receptor sensitivity, to GLP1 agonists. That is, they receive a drug of this class, but their receptors do not bind it. Genetic factors are still implicated, or differences in genes related to appetite, or even the metabolic profile of the patient itself, they may have very severe insulin resistance and not respond. Also, failure to achieve a therapeutic dose due to adverse effects, e.g. nausea or vomiting. So he needs to either substitute the treatment, or even discontinue it prematurely.
Ερ: Is there any way to predict a patient’s resistance to treatment? Are biomarkers being sought at the study level to indicate who will lose fat and who will lose muscle mass?
Ab:This is perhaps the most timely question, not only for patients, but for all doctors who deal with obesity. We cannot accurately predict before treatment whether the patient will respond. There is currently no clinically established biomarker that is predictive. However, clinical trials are underway testing biomarkers that will predict whether the patient will have resistance and whether they will lose muscle mass or fat. We do not yet have any published data, but we await the results with great interest. In clinical practice, there is a device that measures body composition, i.e. percentage of fat, muscle mass, cell mass, and water, as well as the rate of metabolism. And from that we can clinically deduce whether there is insulin resistance. Two or more measurements tell us whether the patient is losing muscle mass or fat, and thus, we determine if there is a response to treatment.
Ερ: Right now how much of the weight lost is fat and how much is muscle mass?
About:In clinical studies, fat mass can have a loss of 65-80% and lean mass can have a loss of 20-35%. But these percentages have been extracted from people who followed diet and exercise programs, were not elderly and received adequate protein.
Contraindications and limits of medication-What we know about long-term use
Ερ: If you had to set a limit, who shouldn’t be on these drugs
App: There was a blurry landscape here, which now seems to be clearing up. There are categories of patients who cannot take this treatment, including people over 75 years of age, pregnant and breastfeeding women, people with a history of myeloid carcinoma of the thyroid, people with recurrent episodes of pancreatitis and people allergic to the active substances in question. However in some other cases we can give the drug sparingly and monitor patients closely. That is, with caution, people with cholecystitis and cholelithiasis, people with a history of food intake disorders and people with gastroparesis can receive the medication. Patients with a body mass index below 27 without co-morbidities would normally be tested first with diet and exercise.
Ερ: Is there data for use over 3-5 years?
Ab>About: For substances such as semaglutide we have two years of studies and real world data, i.e. field studies, of 4 years. For older drugs in the class such as liraglutide we have over five years of data. For newer drugs like tirzepatide there is no long-term data because it is very recently launched and so we are waiting for the results.
Ερ: What is the future of these drugs? What will be the next generation drugs and when are they expected?
App: The future of these drugs is bright. Obesity is now medicated and this is a great first victory. There are drugs right now that are in phase 2 and 3 studies, or already approved by the FDA and EMA, and are expected in our country. Two of them that will be released in the next few months will also be available in tablet form, which will make it easier for patients to comply, since it will be easier to take.
