Latest developments in causes and treatments



Does Ozempic Cause Weight Loss by Impacting the Brain or the Gut?

There is a long history of weight loss drugs that have “off-target” results making them dangerous to use, such as amphetamine-based diet pills. The list of unpleasant side effects is long and bewildering to researchers. It includes rapid heartbeat, gastrointestinal distress, and suicidal ideation. Formulating drugs that have the desired effects of weight loss without harsh or dangerous side effects is a monumentally difficult task.

When it comes to semaglutide, also known as Ozempic and Wegovy, a GLP-1 receptor agonist, there is a lot of uncertainty about how, exactly, the drug impacts digestion and the brain. The issue is the subject of a lengthy thesis by Jennifer Sylvia ten Kulve, a researcher at the European Association for the Study of Diabetes (EASD), entitled The Gut-Brain Axis and the Regulation of Food Intake: The Role of GLP-1, from Physiology to Pharmacotherapy,” published in The Netherlands in 2016.

Kulve’s thesis attempts “to investigate the role [of] glucagon-like peptide-1 (GLP-1) in the central nervous system (CNS) regulation of food intake in humans.” The author works her way slowly through the research to achieve these findings:

  1. GLP-1 drugs cause weight loss by reducing food intake, not by increasing energy expenditure.
  1. Studies in rodents indicate weight loss is due to GLP-1 effects on the central nervous system (CNS).
  1. Next, she examined GLP-1 receptor expression in the postmortem hypothalamus: “We found GLP-1 receptor expression throughout the hypothalamus, including the hypothalamic paraventricular nucleus (PVN) and infundibular nucleus (IFN), both involved in the regulation of energy metabolism.”
  1. Using fMRI, the researchers did brain scans of control subjects and people with type 2 diabetes (T2DM), and “we found that obese T2DM patients have increased activation in CNS areas involved in the regulation of food intake.”
  1. Then they compared the results of injecting T2DM patients with either a GLP-1 drug or a placebo, with fMRI of the results: “Our finding indicates that endogenous GLP-1 has a physiological role in mediating satiety effects in the human CNS, thereby contributing to the central control of food intake.”
  1. In a fascinating comparison, the researchers conducted fMRI on T2DM patients after prolonged treatment with either insulin or liraglutide. Both treatments reduced glucose levels but liraglutide resulted in significant weight loss. At 12 weeks out, liraglutide significantly reduced CNS activity in the area of food regulation compared with insulin patients.
  1. Up to this point, researchers were using images of tasty food to measure brain stimulation. They went one step further and watched the impacts of eating tasty foods on the fMRIs of lean, non-diabetic subjects and T2DM subjects, and found that “T2DM patients have a reduced responsiveness to the consumption of palatable food, which may induce larger palatable food consumption in order to compensate for this deficit.”
  1. The researchers found that liraglutide reduced the activation of the food regulation portion of the brain in lean, healthy individuals but not in T2DM subjects. “This suggests that endogenous GLP-1 is a physiological signal contributing to central rewarding effects of the consumption of palatable food in humans.”

Kulve concludes her thesis with this statement:

Our observations indicate that endogenous GLP-1 contributes to the physiological regulation of food intake via effects in CNS.

That sounds fairly definitive, but there was not much in this thesis about the role of the gut and liraglutide’s impact on the gut. Specifically, does liraglutide cause sub-clinical nausea that is the source of appetite suppression? Unfortunately, that question remains to be answered. We’ll keep looking at AddictionNews.

Written by Steve O’Keefe. First published June 26, 2024.


“An Historical Review of Steps and Missteps in the Discovery of Anti-Obesity Drugs,” National Institutes of Health, July 2022.

“The Gut-Brain Axis and the Regulation of Food Intake: The Role of GLP-1, from Physiology to Pharmacotherapy,” by Jennifer Sylvia ten Kulve, published by VU University Medical Center, The Netherlands, 2016.

Image Copyright: Wikimedia Commons, used under Creative Commons license.


Your email address will not be published. Required fields are marked *