How to keep Ozempic/Wegovy weight loss without the nausea

Drugs that work by way of the GLP-1 system are broadly prescribed for sort 2 diabetes and weight problems. They imitate a pure hormone launched within the digestive tract after consuming and sign the mind to cut back starvation. Though these medication are efficient, as much as 40% of individuals taking them expertise negative effects equivalent to nausea and vomiting, which frequently result in stopping therapy. Scientists at the moment are analyzing whether or not the useful actions of GLP-1 medicines will be separated from the uncomfortable ones, and whether or not these medication may need further therapeutic functions.

Key New Findings Throughout Mind and Conduct

At present’s new findings present that:

Combining low doses of the drug tirzepatide, a “twin agonist” that works, partially, by activating GLP-1 receptors, with the hormone oxytocin ends in weight reduction with out gastrointestinal negative effects in overweight rats. (James E. Blevins, College of Washington)

Nerve cells within the space postrema — the mind’s vomit middle — are necessary for each weight reduction and nausea in response to GLP-1 medication in mice. (Warren Yacawych, College of Michigan)

In mice, activation of GLP-1 receptors on cells within the central amygdala prompts a newly recognized mind circuit that suppresses alerts driving pleasure-based consuming. (Ali D. Güler, College of Virginia)

GLP-1 receptor agonists suppress thirst in addition to urge for food, and a area within the forebrain of rats referred to as the median preoptic space seems to be concerned on this impact. (Derek Daniels, College at Buffalo)

“Analysis demonstrates an impact of those medicines on the mind past treating diabetes and weight problems, through mechanisms which can be nonetheless not absolutely understood,” says Lorenzo Leggio, MD, PhD, a physician-scientist and medical director of the Nationwide Institute on Drug Abuse (NIDA), a part of the Nationwide Institutes of Well being. “GLP-1 therapies seem to have a number of synergistic results that could be helpful for treating persistent ailments with overlapping neural mechanisms, together with binge consuming issues and addictive issues.”

This analysis was funded by nationwide companies together with the Nationwide Institutes of Well being (NIH), the Division of Veterans Affairs (VA), and personal organizations. The authors are solely liable for the content material, which doesn’t essentially symbolize the views of NIH or VA. Media credentials are required for full in-person and on-line entry to Neuroscience 2025.

Highlights From the GLP-1 Press Convention

• GLP-1 medicines successfully deal with sort 2 diabetes and weight problems by curbing starvation, however these medication typically trigger gastrointestinal negative effects like nausea and vomiting, in addition to decreases in different motivated behaviors like thirst.
• Working with rodent fashions, analysis demonstrates that GLP-1 medication have an effect on reward processing within the mind, and ongoing efforts are working to cut back the gastrointestinal negative effects of those medication.

Oxytocin Might Improve Tirzepatide’s Weight-Loss Advantages

James E. Blevins, Summary PSTR033.02

• Tirzepatide (TZP; Mounjaro®) is a twin GLP-1 receptor (GLP-1R)/glucose-dependent insulinotropic polypeptide receptor (GIPR) agonist authorized for weight problems and sort 2 diabetes, however it might probably additionally result in nausea, vomiting, and lack of muscle mass. Oxytocin, a hormone identified for its function in social conduct, can scale back body weight with out inflicting nausea or vomiting.
• On this examine, overweight rats have been handled with low doses of TZP mixed with oxytocin. Researchers monitored modifications in body weight and kaolin consumption — a delicate clay animals devour when nauseated — over 28 days.
• Oxytocin and low-dose TZP every produced a 6-7% discount in body weight when used alone, however the mixture almost doubled the impact to 11%. Meals consumption and physique fats mass decreased with out a rise in kaolin consumption, indicating the absence of gastrointestinal discomfort.
• These findings counsel that pairing oxytocin with decrease doses of TZP could promote weight reduction whereas minimizing disagreeable negative effects.

Pinpointing the Mind Area Chargeable for Each Nausea and Weight Loss

Warren Yacawych, Summary PSTR083.12

• GLP-1 receptor agonists scale back starvation and help weight reduction by way of actions within the mind. Nevertheless, in addition they steadily trigger nausea and vomiting. To know how these results are managed, researchers examined two key mind areas: the nucleus tractus solitarius (NTS) — concerned in satiety — and the realm postrema — concerned in vomiting.
• Though NTS cells containing GLP-1 receptors naturally assist regulate body weight, immediately concentrating on this area with GLP-1 receptor agonists didn’t result in weight reduction. In distinction, concentrating on the realm postrema — the mind’s vomit middle — produced each weight reduction and nausea.
• The outcomes point out that the realm postrema is central to each the useful and unsightly results of GLP-1 receptor agonists. Separating urge for food suppression from nausea shall be a significant focus for enhancing these medicines.

A Newly Recognized Mind Circuit That Dampens Reward-Pushed Consuming

Ali D. Güler, Summary PSTR151.06

• GLP-1 receptor agonists can scale back urge for food and body weight, however the exact neural pathways behind these results are nonetheless being mapped. Utilizing genetically engineered mice, researchers demonstrated that GLP-1 medication affect two main mind programs: one which regulates starvation and one other that reduces cravings for extremely “rewarding” meals.
• The staff studied GLP-1 receptor-expressing cells within the central amygdala. When activated, these cells lowered meals consumption. They ship alerts to the ventral tegmental space, which is necessary for dopamine responses to “rewarding” stimuli.
• Activation of those central amygdala neurons lowered dopamine exercise on this reward circuit, revealing a pathway that connects the amygdala, brainstem, and midbrain. This circuit seems related to pleasure-based consuming, binge consuming, habit, and different circumstances involving reward-related behaviors.

How GLP-1 Medication Affect Thirst and Hydration Alerts

Derek Daniels, Summary PSTR083.03

• GLP-1 receptor agonists lower thirst along with lowering meals consumption. Brattleboro rats, a particular laboratory pressure, are particularly delicate to this thirst-suppressing impact.
• Researchers noticed that mind areas concerned in thirst — together with the nucleus of the solitary tract and the median preoptic space — confirmed vital modifications in GLP-1 receptor expression after thirsty Brattleboro rats have been rehydrated.
• These outcomes provide perception into why GLP-1 medication have an effect on thirst and should information the event of medicines that preserve metabolic advantages with out altering hydration behaviors.