Effect of tirzepatide on excess weight: what about patients with an eating disorder?

The blog of Dr. Boris Hansel – Diabetologist and nutritionist

Presented at the 2022 American Diabetes Association (ADA) Convention, the SURMOUNT-1 study ^[1] demonstrates a remarkable efficacy of tirzepatide treatment in weight loss. But what about these patients who suffer from eating disorders and who constitute a large part of obese people? The comments of Pr Boris Hansel, diabetologist and nutritionist.

TRANSCRIPTION

“A few days ago the quite incredible effects of tirzepatide in the treatment of excess weight were revealed. What should we remember about this? Interesting link with the laboratory that develops this drug, nor with the laboratories that develop or market molecules of the same therapeutic class.

incretinomimetics

Tirzepatide is a drug of the incretin family. As a reminder, these are molecules that are naturally produced by the digestive tract and are known to stimulate insulin secretion in response to rising blood sugar in the first place. There are also incretins used as medicine that are analogous to these natural incretins and that have these same effects, in addition to an interesting effect in therapy that consists of slowing down gastric emptying and an effect at the brain level. All this reduces appetite and promotes weight loss.

We know and use liraglutide, which has an MA in type 2 diabetes, but also an MA in obesity and overweight with risk factors. Semaglutide is known, which is also prescribed in the context of diabetes and more recently with an ATU (temporary authorization for use) in massive obesity, in specific cases. We know of dulaglutide and exenatide, which are also GLP1 analogues that have no indication in obesity but do have an indication and MA in type 2 diabetes. These molecules continue to have a favorable effect on weight. So this whole class of GLP1 analogs has a favorable effect on weight.

The novelty of tirzepatide

What about tirzepatide? Schematically we can give two news:

• it is the first drug that has two “incretin” effects: an anti-GLP1 effect since it is a GLP1 agonist and also a “GIP” effect since it is also a GIP agonist. In fact, there are two agonists in the same drug. The effect on diabetes has previously been shown in clinical trials, but what’s new in the SURMOUNT-1 study?^[1] recently published, is a remarkable effect on weight loss in patients who are not diabetic. So we already had the information in diabetic patients, but here we have evidence in obese patients, or overweight patients with cardiometabolic risk factors, that it works, even if they are not diabetic. A few words about this SURMOUNT-1 trial: 2539 patients, obese or overweight with an obesity-related abnormality, were included. After randomization, they were divided into four groups to receive tirzepatide at a higher or lower dose (groups 1, 2 and 3), or a placebo (4^me band). The results are clear and long term. We notice weight loss that is rapid in the first few months, continues, and eventually plateaus. Weight loss of 21% is observed with the maximum dose of tirzepatide, compared to 3% with placebo at 72 weeks and in the intention-to-treat analysis.

• Another pretty mind-boggling number: 40% of the people who got the highest dose of tirzepatide had at least a 25% weight loss in the on-treatment analysis—that is, in the patients who actually took the drug. In fact, this has never been seen in clinical trials with the drugs proposed for obesity, in studies obviously without surgery.

Side effects

What are the side effects ? It is not very surprising. We found nausea, vomiting, as we are used to seeing with GLP1 agonists already used in routine care.

Another important element: no side effects on mood or on the heart, as we have seen with previous drugs. We remember certain drugs that favored depression and suicide attempts, others that could act on the heart, especially on the heart valves. Here, nothing, no ulterior motive with tirzepatide.

Is tirzepatide the long-awaited solution to treat obesity?

You have felt my enthusiasm. But in my opinion, it is still necessary to give some precisions:

• First, be aware that there are significant interindividual variations with tirzepatide. There were clearly responders and non-responders in the trial, without it being possible to predict who will benefit more from this treatment.

• Second element that I would like to insist on: we must remember that obesity is a multifactorial disease. This disease is associated, in 40 to 60% of patients, with eating disorders, whether they are bulimic crises, bulimia or Binge eating disorder called binge eating. Be careful though, no one really pointed this out in the SURMOUNT-1 study comments, but patients who had eating disorders were not included in the study. What would be the impact of tirzepatide in these patients who represent a large proportion of obese patients? Impossible to answer today. And if we look at the effect of other GLP1 agonists and their impact on eating disorders, there is very little literature on that. When looked at closely, liraglutide may reduce cravings and potentially binge eating in the short term, but this does not appear to hold up in the long term and there is little to no data with other GLP1 agonists. So it will be necessary to remember, if the drug is available, which is not in great doubt: its interest in obesity, in patients with an eating disorder, is something that is far from being validated.

Thank you for watching and see you very soon at Medscape.”

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