What makes losing weight so difficult for extremely overweight people?
Matthias H. Tschöp: Our genetics are not made for us to be able to maintain our weight in times of broad calorific abundance and predominantly sedentary activities. In order to store calories our body has many signals that prevent weight loss attempts.
How can molecules similar to natural digestive hormones and used in a different dosage for type-2 diabetes help with this?
Tschöp: Two insights were important: Obesity is a brain disorder – and it’s there that we have to change a combination of signals. The superhormones that ultimately led to the breakthrough are longer and more effective than natural peptides. They activate various receptors in the brain and thus encourage weight loss in several ways. Predominantly they regulate appetite and satiety in the brain and also improve insulin sensitivity.
In this way, they not only appear to slow down the irresistible cravings for chocolate bars, but also the desire for alcohol, and it is also possible they are effective against gambling addiction. We have to stay on this, in order to understand all contexts.
Your research was particularly focused on molecules containing multiple hormones. Why can these do more than one hormone alone?
Tschöp: In combination they have an enormous synergistic potential, they act together in the brain. On top of this, they have fewer side effects.
Doesn’t willpower work too then, if losing weight is “in the mind”?
Tschöp: Some lucky people’s genes gift them a metabolism which makes this easier. Appealing to an extremely overweight person’s willpower is very inappropriate, akin to telling people with depression to “pull themselves together”. Gene therapy, however, is promising for real healing. Until then we have to be thankful that we have these new medications, as they also prevent secondary diseases such as diabetes.
In the meantime there is also a demand among non-overweight or slightly overweight people who can afford the medication. Celebrities are talking about it. Does this worry you?
Tschöp: So long as the availability of the medication is limited, it should be provided to those who need it the most. Doctors play an essential role here: They are responsible for ordering the prescription-only medicines. As a matter of fact, the triple-agonists, coming soon, appear to function the best in massively overweight people.
Until then, the drugs must be injected weekly. When will there be a “weight loss pill”?
Tschöp: There are various new developments, 20 to 30 compounds are in the pipeline. However, they must be given in high doses to ensure that the peptides do not dissolve in the gastro-intestinal tract. “Small molecules” which directly dock at the receptors are currently even less effective.
More crucial than the question “injection or pill” is, in my opinion, another: Do you really want to take an extremely effective yet expensive medication for the rest of your life? We need lighter, milder medications for weight maintenance programmes. A second challenge for research is the specific protection of muscles. Using the new medications to lose weight will also always mean a loss of muscle mass to some extent.
The interview was conducted by Adelheid Müller-Lissner