Background: Ozempic, Wegovy, and Semaglutide
Ozempic...It has been taking over the news recently with its seemingly miraculous results. Ozempic, also known as semaglutide, was first approved as a medication for diabetes at a max dose of 2mg.
When patients were losing significant amounts of weight while taking it for diabetes, the manufacturer, Novo Nordisk, continued research for its use in obesity. This means that the drug was studied in individuals who had a high weight who did not also have diabetes.
Now, the medication has separate FDA approval for its use in obesity in adults. For its use in obesity, it is called Wegovy and has a max dose of 2.4mg. There is no difference between the ingredients in Ozempic and Wegovy. The difference lies in the fact that the different names are used for different medical indications, and the max dose that is used for each indication differs.
Getting the Prescription for Ozempic and its Results
Now that the drug has been around enough time for people to try it out, some find that they lose a lot of weight, and others discover they do not lose much or any weight. They are frustrated and wonder, "why am I not losing weight on Ozempic?"
To get more of an understanding on this, it is important to look at semaglutide's weight loss results in studies.
STEP Trials on Semaglutide: How Well it Works in the Research Setting
The STEP trials are the series of studies on semaglutide 2.4mg for obesity conducted by the drug maker Novo Nordisk. These studies all varied somewhat in size, population they examined, and in some of the research outcomes they were looking at. As part of the study protocol, those taking the drug and those in the placebo group received nutrition counselling. At the end of the studies, the groups taking semaglutide had lost weight in the range of around 10-17% of body weight. What this means, is that a person who started at 250 lbs may have finished the study at around 215 lbs.
To help put this into perspective, there was a range of how well it worked for different people. Some people lost more weight, and some people lost less weight. Looking at how semaglutide works in the body may give a clue as to why there is a range of effectiveness.
How Semaglutide Works
Why does the drug seem to work well for some and not for others? I think the answer might lie in how the drug works in the body, also known as its mechanism of action.
Semaglutide is a GLP-1 receptor agonist. That means it activates a receptor called GLP-1. These receptors are located in many areas of the brain, but are relevant to this medication in the hypothalamus. In the hypothalamus are neurons with this receptor that mediate satiety and hunger. Semaglutide also leads to the reduction of two neurotransmitters, agouti-related protein and neuropeptide Y, that act as hunger signals. Finally, semaglutide has effects on the hedonic reward system, which is how people seek certain experiences, such as food, for the sake of pleasure.
Let's look at how this mechanism translates to human experience and behavior. Studies have found that semaglutide leads to decreases in hunger, increases in fullness, increases in satiety, and decreases in prospective food consumption. This leads to an overall appetite suppression, and importantly, a 35% energy intake reduction in studies. People taking the medication reported reduced food cravings and increased control of eating. The had less desire and fewer cravings for sweet, savory, and dairy foods.
Why does Semaglutide Work Better for Some People and Worse for Others--Why am I Not Losing Weight on Ozempic?
Understanding the mechanism of action and how it translates to peoples' experience and behavior around food may explain why it works for some people and not others. I have not found studies that have tried to parse out who semaglutide works for and who it does not work for. This is my own theory based on understanding the scientific research thus far.
I think that it is important to understand the cause of a person's obesity. There are many factors that lead to obesity, and usually people with obesity have a variety of these factors. Certain factors being more prominent in a person's obesity may explain why they are or are not seeing weight loss on semaglutide.
If a patient's obesity is due to higher calorie intake that is caused by having an increased appetite, many cravings for food, and a strong hedonic reward system, then they might be the ones semaglutide works for, as semaglutide targets all of those factors. In contrast, if a person is obese, but they do not experience cravings, their appetite is average at baseline, and hedonics play a smaller role for them, then maybe semaglutide will not work for them.
An additional factor, which plays a role in a very small percentage of the population of individuals with obesity is what is called monogenic obesity, or obesity caused by a specific genetic mutation or change. If a person has a genetic change that impairs the function of the GLP-1 receptor system, then it is possible that semaglutide will not work for them.
Finally is the issue of nutrition counselling. In the studies, participants received individualized nutrition counselling. Unfortunately, many people who are taking semaglutide now are not receiving concurrent nutrition counselling. Eating an appropriate diet, even in the setting of decreased appetite, is key to weight loss for many people.
Final Thoughts...Why am I Not Losing Weight on Ozempic
A final question of those who do not see weight loss while taking semaglutide might be, "Why am I obese, then?" As a dietitian who has been in practice for 8 years, I know now better than I knew at the start of my career that I do not fully know the answer to this question. We can state the factors that we do know: genetic predisposition, medical conditions, certain medications, environment, finances, physical activity, sleep, and social determinants of health. Some of these factors have better understood potential mechanism of influence on weight than others. But all will hopefully be better explained with further research.