Although their clinical benefits for cardiometabolic, renal, hepatic, and obesity treatment seem too good to be true, GLP-1 and GIP receptor agonists from the incretin therapeutic class are becoming increasingly viable for a range of diseases. It has been proven to be a pathway-targeting drug. Chronic disease.
Even for indications like mental illness, drugs like semaglutide (Ozempic) may be more reliable than a pipe dream.
In the second segment of the interview, HCP Live At the 2024 Annual Meeting of the American Psychiatric Association (APA), Roger S. McIntyre, MD, Professor of Psychiatry and Pharmacology at the University of Toronto, announced the We discussed specific prospects. He explained that the rationale begins with understanding the “disproportionate” consumption of energy from the brain. Although the brain makes up about 5% of the body’s weight, it consumes about 25% of the body’s total energy.
“So they’re very susceptible to things like oxidative stress,” McIntyre says. “And GLP-1 has been shown to have antioxidant effects, in addition to its anti-inflammatory and neuroprotective effects. And the antioxidant capacity of these drugs is, of course, ringing a therapeutic bell. Maybe there’s some opportunity, but we’re also scratching our heads, “Does this all mean it’s related?” Can changes in GLP-1 signaling cause psychiatric disorders?”
McIntyre said there is at least some evidence to support that hypothesis. First, there is growing data showing that patients receiving GLP-1 agonists for conditions such as diabetes have a significantly reduced risk of depression and cognitive problems.
“In other words, it gives us reason to believe that they are protective, but indirectly that maybe GLP-1 dysregulation is not just associated, but causative. “It also tests the hypothesis that it is not possible,” McIntyre explained. “Because we know that mental disorders are heterogeneous in terms of causation and pathology. Perhaps this is one of the suspects in the causal category.”
When asked about what exactly he hopes late-stage clinical trials evaluating drugs like semaglutide for conditions such as depression and alcohol use disorder will involve, McIntyre said, patient-reported measures of disease severity and behavior. He said that it is likely to include standard results such as. , heavy drinking days, etc.). However, more “conceptually supported and mechanism-based” trials may consider the opportunity to prevent deterioration in psychiatric health: GLP-1 agonists may slow disease progression in early-stage patients. Can it be delayed?
“Let’s say you get a little older and start to have mild cognitive impairment. If you take one of these drugs, could you slow the progression of Alzheimer’s disease?” McIntyre said. Ta. “That would be interesting. Secondly, if you’re someone who has depression or bipolar disorder, for example, and you’ve taken any of these drugs over the next six, 12, 18 months. If so, will the disease be less likely to come back?”
McIntyre advised his colleagues to consider two paradigms of treatment outcome in such studies: the acute symptom-reducing effects of a drug class and the opportunity to prevent progressive disease.
“Taken together, the science about GLP-1 and GIP (agonists) gives us some reason to believe that they are part of an arc that is the trajectory of areas of psychopathology such as cognitive impairment, reward impairment, and motivation. ” he said. “So I think of this as an acute treatment paradigm. Look at people with alcohol use disorder. Are they reducing their alcohol intake? That’s certainly a very valid paradigm. But I’m particularly interested in changing the trajectory of cognitive impairment and people at risk for it, and perhaps changing the trajectory of relapse vulnerability for people at risk over time. I’m interested.”
