How Does Semaglutide Work for Weight Loss?

When trying to lose weight, we often make lifestyle changes, adding exercise to a diet of more fruits and vegetables, lean proteins, and healthy fats. We cut back on fast food and junk food, all the while dreading hunger pangs and that nagging voice, “Hey, I’m still hungry!” 

What do we do? Sometimes we turn to higher-calorie foods that our bodies can’t stop craving. 

There are reasons why our bodies crave more, gain more, and—try as we might—have trouble losing and keeping weight off. The most common reasons are genetics, physical or mental illness, and metabolism. You’ve probably heard about basal metabolic rate (BMR), which is the rate your body burns calories while resting. Tests show that people with a faster metabolism naturally burn more calories than people with slower metabolic rates. 

When calories aren’t all burned—or metabolized—our bodies use a mechanism to store excess calories in cells. You see, our bodies never know for sure when our next meal will arrive. Unfortunately, when our bodies sense a lack of food (for example, when dieting or fasting), our metabolic rate slows. Obviously, that’s not what we’re looking for when we’re trying to lose weight. 

The process of metabolism involves insulin, a naturally occurring hormone produced in the pancreas. When we consume calories, insulin directs the body’s cells to take in glucose from the bloodstream. As glucose moves into our cells, blood glucose levels lower. This solves the problem of prolonged high blood glucose levels that may cause problems, like type 2 diabetes. 

It turns out that a medication called semaglutide, a glucagon-like peptide (GLP-1) receptor agonist might be our best weight-loss friend. Semaglutide increases insulin secretion, which is good for people living with type 2 diabetes. It’s also good for people who are overweight or obese. Semaglutide also helps eliminate pangs of hunger that cause us to overeat and snack.

The human body has a goal to maintain homeostasis, always fighting to keep its equilibrium. We exercise and cut high-calorie foods, but our bodies tell us, “Wait, I don’t want to change!” So, we eat, and then we feel bad because we can’t ignore food cravings.

Don’t feel bad! It’s just our body’s mechanism working to maintain stability. Do not worry, either. Worrying about cravings only drags us down, adding emotional strain that can thwart our efforts to lose weight. 

We now know that semaglutide may help.

If you are living with type 2 diabetes, you might already be taking a semaglutide medication. If you do not live with type 2 diabetes, semaglutide is now available to combat weight loss for some non-diabetic people. This means that you may now use medication to help combat cravings in your fight to lose weight. 

The History of Semaglutide History 

A team of researchers working for the pharmaceutical company Novo Nordisk first developed a semaglutide drug in 2012. The medication, later named Ozempic, had previously run a series of clinical trials to test its efficacy—its desired results—as a longer-acting alternative to liraglutide. Why? Because liraglutide wasn’t FDA approved for the estimated 30 million people living with type 2 diabetes whom researchers knew would benefit from a longer-acting blood glucose control. 

Liraglutide is a type of medication similar to semaglutide, and both are GLP-1 receptor antagonists. GLP-1 receptor antagonists help people with type 2 diabetes control their diabetes as a periodic therapy. However, all new medications must go through clinical trials to confirm efficacy before getting FDA approval. This takes time.

Another Novo Nordisk clinical trial revealed that semaglutide could treat type 2-related obesity by reducing food cravings and hunger. This semaglutide could also reduce body fat. It was exciting, prompting a second clinical trial, a phase 3 randomized controlled trial. This new trial found that a once-weekly injection, or 2.4 mg. of the drug, resulted in an average reduction of −14.9% body weight at 68 weeks. In real terms, that’s like a 200-pound individual shedding up to 30 pounds! 

With FDA approval in 2017, Novo Nordisk began marketing the medication under the name Ozempic. 

Semaglutide Uses

People who need help to control their type 2 diabetes with a semaglutide take either Ozempic, Wegovy, or Rybelsus. The drugs offer some great benefits. In addition to weight loss, the once-weekly self-administered shot can help reduce the risks of type 2 diabetes-related cardiovascular events and also maintain lower blood glucose levels.

Of course, there are other GLP-1 medications, like Trulicity, but they don’t contain semaglutide. Therefore, users don’t experience such high weight loss results.

How Semaglutide Medications Help Lower Weight

Called “incretin mimetics,” semaglutide mimics the hormone called “glucagon-like peptide-1” (GLP-1). The GLP-1 hormone targets the areas of the brain that regulate food intake and appetite. Some professionals call it a ‘hunger hormone’ because the hormone makes us feel full. 

The pancreas plays an important role in regulating how another hormone, insulin, works. Remember, homeostasis is the body’s way of maintaining equilibrium. When we eat a meal, we are ingesting calories that raise our blood glucose (sugar). The pancreas in non-diabetic people reacts by secreting insulin. Insulin helps maintain a balanced blood glucose level. Balance is homeostasis.

Think about how you contemplate the prospect of eating a favorite food. You can’t wait. But at a certain point you begin to feel full. In fact, at some point, you’re so VERY full, you can’t eat one more bite. Ugh!

This is homeostasis, thanks to insulin and the process of metabolism. It’s the body’s way of managing food intake so that we don’t overeat.

How does a healthy pancreas know that it needs to get to work? Amazingly, the gastrointestinal tract (gut) responds to food intake by signaling to the pancreas, instructing it to begin releasing insulin right now. It’s called the incretin effect. 

When the gastrointestinal tract recognizes glucose, incretins are sent out to the pancreas. Immediately, the pancreas recognizes the incretins and begins releasing (or holding onto) the right amount of insulin needed to match the glucose. 

In other words, incretins prevent us from developing hyperglycemia (high blood glucose). Now we understand the pancreas’ reaction to eating. But how does our gut initially recognize caloric intake? 

The intestine produces intestinal mucosa made up of two incretin peptides, glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide 1 (GLP-1). The incretin effect begins with these two peptides. 

The body’s peptides, though, react differently to blood glucose. GIP suppresses glucose secretion by managing the release of insulin as needed (not too much, not too little).

Meanwhile, the GLP-1 receptor agonists move from the gut to the pancreas to meet with and stimulate the GLP-1 receptors. The receptor agonists basically say, “Hold onto some of that insulin for a while so we can take in the food’s nutrients.” 

People with type-2 diabetes have GLP-1, but the incretin effect usually doesn’t work properly. Their blood glucose increases because the pancreas doesn’t recognize GLP-1. Think of this communication disruption like your cell phone when you’re on a mountain road: dropped calls happen.

What about people who don’t have diabetes? In non-diabetics, GLP-1 is well-connected; it always knows our blood glucose levels. There aren’t any mountains interfering with communication. 

GLP-1 also helps slow down the process of emptying the stomach. This is helpful when we diet because we feel full longer. When we feel full longer, then we don’t want extra snacks.

In response to a meal, the gastric inhibitory polypeptide (GIP) already began its work from the pancreas. When blood glucose levels rise during and after eating, GIP intensifies insulin release both immediately and later—as needed.

(Source: Wikipedia Commons)

Incretin Effect: The gut recognizes food and releases GLP-1 receptor agonists that meet up with the GLP-1 receptors in the pancreas. Now, glucose regulation begins as insulin moves into the bloodstream to lower blood glucose levels while simultaneously inhibiting glucagon (sugar) release. 

GIP, living in the pancreas, helps regulate glucagon release. In a well-working system, GIP knows when to hold on to glycogen, and when to release glycogen.

Also in non-diabetics, GIP only stimulates glucagon secretion at low glucose levels, causing researchers to propose that GIP has another function. 

• First, GIP stabilizes blood glucose levels by secreting glucose to control hypoglycemia (low blood glucose).
• Simultaneously, GIP also secretes insulin to lower hyperglycemia (high blood glucose).

In other words, GIP is a very smart stabilizer. 

The FDA unanimously approved semaglutide for use by non-diabetic patients in 2021. This means that if you don’t have diabetes, but you struggle to control weight, you may now also take semaglutide, administered by injection or orally. 

You will need to meet the requirement for non-diabetics: those with a BMI of 30 kg/m2 or greater may now be prescribed semaglutide. 

Conclusion

Semaglutide performs a complicated job involving the pancreas, gut, brain, and more. It’s a process that makes us shake our heads and say, “No wonder losing weight is such a battle.” The body isn’t just smart, it’s a hard worker, too, always striving to attain and maintain homeostasis. This makes losing weight difficult. It’s good to know you may have the power of semaglutide on your side.