How GLP-1s Work: Weight Loss Medication

GLP-1 medicines are being hailed as the new wonder drug of the 21st century. Almost unheard of as recently as a decade ago, they’ve come from (seemingly) nowhere to be hailed as the 2023 ‘Breakthrough of the Year’. In May 2024, research showing that the weight loss treatments may also reduce the risk of cardiovascular ailments like heart attack and stroke by a significant amount has led to some writers proclaiming them the biggest medical advancement since cholesterol-lowering statins appeared in the 1990s.

The buzz surrounding drugs like Ozempic, Wegovy, Zepbound, and Mounjaro has seen them become household names; you’ll find talk of them everywhere from scientific journals to Jimmy Kimmel discussing which celebrities may be using them. But how do they work? Let’s take a look.


The story of GLP-1 medication has its origin in the 1970s. Then, scientists were looking at how peptides could help regulate glucose in the body after eating meals. The idea was to increase insulin production to avoid blood sugar levels spiking, primarily as an aid to managing diabetes. In the 1980s, the effects on insulin production of the hormone GLP-1 were noticed. Pharmaceutical companies like Eli Lilly and Novo Nordisk rationalized that if they could make products that could have the same effect in upping the rate of insulin that the pancreas produced, they could stabilize diabetic patients’ sugar levels, lowering the risk of problems associated with the condition, like hyperglycemia and even diabetic coma. The first GLP-1 medicine – liraglutide, which goes under the brand name Saxenda – was approved by the FDA for diabetes patients in 2010.

Weight loss

While GLP-1 drugs were not originally designed to help with weight loss, the clinical trials involving them showed subjects shedding an impressive amount of body mass. Liraglutide trials showed patients losing around 8% of their body weight. This led to the manufacturers trialing the medications specifically for weight loss in users without diabetes. Semaglutide – the active ingredient in Wegovy – saw patients lose an average of 15% of body weight by the end of a 16-month trial. The FDA approved Wegovy as a weight loss aid for patients with a BMI of 30 or higher in 2021.

GLP-1 medicines work by slowing the progress of food through the digestive system. They’ll keep the user feeling fuller for longer, which means that the user will snack less, and eat smaller portions at mealtimes. The caveman in us will prioritize and prize high-calorie foods as a hunter-gatherer cannot be sure of their next meal. Supermarkets have evolved more quickly than our neurological structure, so the weight loss medication works with the reward pathway in the brain, dulling cravings for unhealthy foods.


For probably too long, being overweight has been viewed by society as a moral deficiency on the part of the individual, rather than as a legitimate medical condition. Meanwhile, the average American is now around 30lbs heavier than they were in the 1960s, with obesity rates tripling in the same period. It’s true to say that GLP-1s aren’t a cure-all. They should be accompanied by a nutritional plan and a schedule of physical activity. However, we must be realistic; in today’s busy world, there will be times when eating healthy can be difficult, and if some additional help can be had in resisting that donut, or passing up the sugar-drenched coffee shop beverages in favor of a regular cup of joe, then it would be remiss to dismiss it out of hand.

GLP-1 medicines fit into a busy lifestyle. Saxenda, Wegovy, and Zepbound are administered by the user, via a once-weekly pre-dosed injection. Naltrexone-Bupropion can be taken as a twice-daily pill for those less confident of needles. As a long-term program, GLP-1s allow patients to work on their behavioral cues, attitudes, and triggers to food, helping them achieve and maintain weight loss. The results so far have been stunning – and with a new treatment under the working title Retatrutide showing weight loss of 60lbs, or 24% of patients’ body weight in current trials – expect them to play an even weightier role in the fight against fat going forward.

Adrian M. Ferguson
Adrian worked as a journalist for 7 years at a local newspaper. Switching to online media, now he covers the latest science news for Wugazi.