Weight loss is a major topic in America- and rightly so. Currently, 40% of Americans are considered obese. We honestly need a major overhaul of lifestyle and our relationship with food. Changes like this are hard, but not impossible. Why is this so important? When you consider that 1 in 5 deaths in the U.S can be attributed to heart disease… that’s pretty important. But not just the endpoint, what about your quality of life when you’re living with physical restrictions? You can change that!
Now I generally feel very strongly about slow, natural weight loss achieved through traditional diet and exercise. The amount of time and energy invested makes you so much more likely to take the changes to heart and stick with it for a lifetime- true lifestyle changes. But when you consider the need to reduce cardiovascular risk, I’d agree that faster is better. Ideally, patients would still take the process to heart (no pun intended) and honestly make lifestyle changes. That’s how you improve quality and quantity of life. So what is this faster process?
You’ve probably heard of GLP-1 injections. Maybe you’ve heard them called weight loss injections. It’s actually a pretty cool thing (and is vastly favorable to previous weight loss medications). It came about the same way that Viagra did (originally a blood pressure medication). A medication was brought about for one intent and a favorable side effect was noticed. Now the medication is used specifically for that reason- in this case, a type 2 diabetes medication is now being used for weight loss. Maybe I’m a nerd, but I think that’s kind of cool. In any event, let’s talk about these medications.
GLP-1 and GLP-1/GIP Receptor Agonists for Weight Loss: A Comprehensive Overview
GLP-1 (glucagon-like peptide-1) and GLP-1/GIP (glucose-dependent insulinotropic peptide) receptor agonists, including tirzepatide, semaglutide, and liraglutide, have become important therapeutic options for weight loss, especially for individuals with obesity, type 2 diabetes, or weight-related health issues. These medications mimic natural hormones that regulate insulin, appetite, and metabolism. Below is a detailed guide, covering all major GLP-1 and GLP-1/GIP receptor agonists.
What is GLP-1 and GLP-1/GIP, and Why Do They Matter for Weight Loss?
GLP-1 (Glucagon-Like Peptide-1):
GLP-1 is a peptide hormone produced in the gut in response to food. It has several key roles:
- Stimulates Insulin Release: After eating, GLP-1 promotes insulin secretion from the pancreas to help lower blood sugar.
- Reduces Glucagon: It suppresses glucagon, a hormone that signals the liver to release glucose, helping to stabilize blood sugar levels.
- Appetite Suppression: GLP-1 acts on the brain to reduce hunger, leading to a feeling of fullness (satiety) and reduced food intake.
- Delays Gastric Emptying: By slowing the rate at which food leaves the stomach, GLP-1 promotes longer-lasting fullness.
GIP (Glucose-Dependent Insulinotropic Peptide):
GIP is another hormone that stimulates insulin release in response to food, but its effect on appetite is less pronounced compared to GLP-1. When paired with GLP-1 in a dual agonist (such as tirzepatide), the combination enhances insulin secretion and metabolism, making it particularly effective for weight loss.
GLP-1 and GLP-1/GIP Medications for Weight Loss
Several GLP-1 receptor agonists and the newer GLP-1/GIP dual agonists are approved for weight loss and/or type 2 diabetes management. These include:
- Semaglutide (Ozempic, Wegovy, Rybelsus)
- Liraglutide (Victoza, Saxenda)
- Exenatide (Byetta, Bydureon)
- Dulaglutide (Trulicity)
- Lixisenatide (Adlyxin)
- Tirzepatide (Mounjaro)
Mechanism of Action
GLP-1 Receptor Agonists:
These drugs work by mimicking the action of GLP-1. They bind to the GLP-1 receptor, which is found in the pancreas, stomach, and brain. This leads to:
- Reduced Appetite: GLP-1 activation reduces appetite by acting on the brain’s appetite centers, helping people feel full with less food.
- Slower Gastric Emptying: These drugs delay the emptying of the stomach, promoting fullness after meals and reducing overall calorie intake.
- Improved Insulin Sensitivity: By enhancing insulin secretion and inhibiting glucagon, GLP-1 drugs help regulate blood sugar, which can also contribute to weight loss by improving metabolism.
- Blood Sugar Control: By improving insulin response and preventing excess glucose release from the liver, GLP-1 agonists help stabilize blood sugar.
Tirzepatide (GLP-1/GIP Dual Agonist):
Tirzepatide binds to both GLP-1 and GIP receptors, which enhances insulin secretion, improves glucose control, and more effectively suppresses appetite compared to GLP-1-only drugs. The combination of GLP-1 and GIP mechanisms provides additional benefits for weight loss and metabolic health.
Who Can Benefit from GLP-1 and Tirzepatide for Weight Loss?
Indications for GLP-1 receptor agonists and tirzepatide include:
- Obesity: These drugs are approved for weight loss in individuals with a BMI ≥30 or ≥27 with weight-related health conditions (e.g., hypertension, type 2 diabetes).
- Type 2 Diabetes: GLP-1 medications help control blood sugar levels and promote weight loss in people with diabetes.
Key Medications for Weight Loss
- Semaglutide (Ozempic, Wegovy, Rybelsus):
- Ozempic: Initially approved for type 2 diabetes management.
- Wegovy: A higher-dose version of semaglutide, approved specifically for weight loss.
- Rybelsus: The first oral GLP-1 medication (semaglutide in pill form), approved for type 2 diabetes management.
- Administration: Ozempic and Wegovy are injected weekly, while Rybelsus is taken orally once a day.
- Efficacy: In clinical trials, semaglutide has shown significant weight loss, up to 15% of body weight over a year.
- Liraglutide (Victoza, Saxenda):
- Victoza: Approved for type 2 diabetes.
- Saxenda: A higher-dose version of liraglutide for weight loss.
- Administration: Daily injection.
- Efficacy: Typically results in 5-10% weight loss.
- Exenatide (Byetta, Bydureon):
- Byetta: Twice-daily injection for type 2 diabetes.
- Bydureon: A long-acting, once-weekly injection for type 2 diabetes.
- Efficacy: 5-8% weight loss in clinical trials.
- Dulaglutide (Trulicity):
- Trulicity: A once-weekly injection for type 2 diabetes.
- Efficacy: Generally results in a 5-7% weight loss.
- Lixisenatide (Adlyxin):
- Adlyxin: A daily injection for type 2 diabetes.
- Efficacy: Similar to other GLP-1s, with 5-7% weight loss potential.
- Tirzepatide (Mounjaro):
- Mounjaro: A dual agonist that targets both GLP-1 and GIP receptors for weight loss and diabetes control.
- Administration: Once-weekly injection.
- Efficacy: Tirzepatide has shown the most significant weight loss results in clinical trials, with up to 22.5% of body weight lost, outperforming other GLP-1 medications in both weight loss and glucose control.
How Are These Medications Administered?
Most GLP-1 and GLP-1/GIP medications are injected, but oral semaglutide (Rybelsus) offers an alternative:
- Semaglutide (Ozempic/Wegovy): Once-weekly injection.
- Liraglutide (Saxenda/Victoza): Daily injection.
- Exenatide (Byetta/Bydureon): Twice-daily or weekly, depending on the formulation.
- Dulaglutide (Trulicity): Once-weekly injection.
- Tirzepatide (Mounjaro): Once-weekly injection.
- Rybelsus: Once-daily oral pill (semaglutide).
Side Effects: What to Expect
Like any medication, GLP-1 and GLP-1/GIP medications can have side effects. Common and serious side effects include:
Common Side Effects:
- Gastrointestinal Issues: Nausea, vomiting, diarrhea, constipation, and indigestion, particularly at the beginning of treatment. These typically subside as the body adjusts. It is very important to eat 3 small meals to help prevent these issues.
- Mood Concerns: Some patients report mood swings, irritability, or even depression while using GLP-1 medications. This may be due to changes in appetite, energy levels, or hormonal fluctuations related to weight loss. It’s essential to monitor mood, especially for individuals with a history of mental health concerns.
- Fatigue and Low Energy: Some users report feeling tired, particularly in the initial stages of treatment.
Serious Side Effects:
- Pancreatitis: There is a rare risk of pancreatitis (inflammation of the pancreas). Patients should seek medical attention if they experience severe abdominal pain, nausea, or vomiting.
- Thyroid Tumors: Animal studies have suggested a risk of thyroid cancer, though this risk has not been conclusively proven in humans. These medications are generally not recommended for people with a family history of thyroid cancer or certain genetic conditions (e.g., MEN2).
- Kidney Issues: Dehydration from gastrointestinal side effects can strain kidney function. Staying hydrated is important, and kidney function should be monitored.
Weight Gain Upon Stopping Medication: The Risk of Rebound Weight Gain
When stopping GLP-1 medications, rebound weight gain is a common concern. These medications help regulate appetite and metabolism, and without them, patients may experience increased hunger and less effective blood sugar control. As a result, weight loss may be regained.
Using GLP-1 Medications as a Tool:
To minimize rebound weight gain, it’s essential to use GLP-1 agonists as part of a long-term lifestyle change. This includes adopting healthier eating habits, regular physical activity, and other behavioral changes that support sustained weight management.
Patient Considerations: Key Takeaways
- Patience and Gradual Progress: Weight loss with GLP-1 medications is much faster than traditional means, but it does still take time and is gradual. Patients should focus on consistent, long-term results rather than quick fixes.
- Side Effect Monitoring: Be mindful of potential gastrointestinal discomfort, fatigue, and mood changes. If side effects are severe or concerning, consult a healthcare provider.
- Long-Term Weight Maintenance: The medication should be used as a tool to help initiate weight loss, but ongoing lifestyle changes (diet and exercise) are crucial for preventing rebound weight gain after stopping the medication.
Conclusion
GLP-1 receptor agonists and the newer GLP-1/GIP dual agonist tirzepatide represent groundbreaking treatments for weight loss, particularly in people with obesity or type 2 diabetes. These medications help regulate appetite, improve blood sugar control, and promote significant weight loss. However, for long-term success, they should be combined with sustainable lifestyle changes. Healthcare providers should monitor patients for side effects and offer guidance on maintaining weight loss once treatment is stopped.
Maybe think about it if you’re in need of some drastic changes. Your health in a really big deal and this is something that you have the power to change and control. And please, let me know if I can help you in any way along this journey. I would be honored to be part of your lifestyle change. Self care should never be ignored and it honestly doesn’t have to be difficult. You’re the one in the driver seat.
