Millions of individuals worldwide face the battle against obesity. Among the latest advancements in weight management are GLP-1 agonists, a class of medications that has gained significant attention in the last few years due to their effectiveness. In this article, we'll explore what GLP-1 agonists are, how they work, their pros and cons, potential side effects, expectations, my personal and professional opinions, and why they are becoming a popular treatment option for obesity.
Considering the numbers and distribution of obesity worldwide, we are in a position where we are in need to treat patients who already suffer from obesity since the impact of obesity on mortality, quality of life, and healthcare costs is immense.
Nearly half (46%) of adults in the U.S. meet recommendations for anti-obesity pharmacotherapy. Only 2% of Obese patients have received treatment, whereas 86% of diabetic adults have received pharmacotherapy, so it is evident that obesity, even though it is a considerably detrimental disease, is not treated equally.
What are GLP-1 Agonists?
GLP-1 (glucagon-like peptide-1) agonists are medications that mimic the action of the naturally occurring hormone GLP-1. This hormone plays a key role in regulating blood sugar levels. These medications were first used and approved as a treatment for diabetes, and physicians and patients alike noticed a considerable effect on weight loss. Since then, the medicines have opened their way to becoming also treatments for obesity in diabetics and non-diabetics.
Common GLP-1 agonists include:
Semaglutide injection (Ozempic® for weight loss, Wegovy® for Type 2 Diabetes).
Semaglutide tablets (Rybelsus® for weight loss).
Liraglutide (Saxenda® for weight loss, Victoza ®for Type 2 Diabetes).
Tirzepatide (Zepbound® for weight loss, Mounjaro® for Type 2 Diabetes
Dulaglutide (Trulicity®).
Exenatide (Byetta®).
Exenatide extended-release (Bydureon®).
Lixisenatide (Adlyxin®).
In this article, we'll focus more on semaglutide since it is the most common/available and the one on which we have more data.
How Do GLP-1 Agonists Work for Obesity?
Understanding how GLP-1 agonists work helps to understand how the naturally occurring GLP-1 hormone works.
GLP-1 is a hormone that your small intestine makes. It has several roles, including:
Triggering insulin release from your pancreas: Insulin is an essential hormone that allows your body to use the food you eat for energy. It lowers the amount of glucose (sugar) in your blood. If you don't have enough insulin, your blood sugar increases, leading to diabetes.
Blocking glucagon secretion: Glucagon is a hormone your body uses to raise your blood sugar levels when necessary. So, GLP-1 prevents more glucose from going into your bloodstream.
Slowing stomach emptying: Slower digestion means that your body releases less glucose (sugar) from your food into your bloodstream.
Increasing how full you feel after eating (satiety): GLP-1 affects areas of your brain that process hunger and satiety.
Reducing GIP (gastric inhibitory polypeptide) production also affects the brain, leading to satiety sensations.
GLP-1 agonist medications work by mimicking this hormone. In medication terms, an agonist is a manufactured substance that attaches to a cell receptor and causes the same action as the naturally occurring substance. In other words, GLP-1 medications bind to GLP receptors to trigger the effects (or roles) of the GLP-1 hormone. The higher the dose of the GLP-1 agonist, the more, the higher the effects.
The satiety effect of GLP1-agonists reduces your food intake, appetite, and hunger. These combined effects often result in weight loss.
The Pros of GLP-1 Agonists for Weight Loss
Clinically Proven Effectiveness: Studies have shown that GLP-1 agonists can result in significant weight loss, especially when combined with a healthy diet and exercise.
Improvement in Metabolic Health: In addition to weight loss, GLP-1 agonists can improve blood glucose control, reduce HbA1c levels, and even lower blood pressure and cholesterol.
Long-Term Benefits: When used correctly, these medications can provide sustainable weight loss and help prevent weight regain..
Convenient Dosage Forms: Many GLP-1 agonists are available as once-weekly injections, making them easy to incorporate into a routine.
The Cons of GLP-1 Agonists for Weight Loss
Cost: GLP-1 agonists can be expensive, especially if they are not covered by insurance. This can be a barrier for many individuals seeking treatment.
Injection-Based: Most GLP-1 agonists require frequent injection (dialy or weekly), which might be uncomfortable or inconvenient for some patients.
Not Suitable for Everyone: These medications aren't recommended for individuals with certain medical conditions, such as a history of thyroid cancer or pancreatitis.
Potential for weight Regain: Weight regain can occur if the medication is discontinued without proper lifestyle changes.
Potential Side Effects
While GLP-1 agonists are generally well-tolerated, some individuals may experience side effects, such as:
*The most common side effects are: (particularly when starting the medication or if you're taking an increased dose.)
Gastrointestinal Issues:
nausea
vomiting
diarrhea
constipation
belching
flatulence
headache
dizziness
abdominal distention
GERD (Gastroesophageal Reflux)
Abdominal pain
Hypoglycemia: This is more likely to occur in patients with diabetes, especially if they are on other blood sugar-lowering medications.
Gallbladder Issues: Some individuals may develop gallstones or gallbladder inflammation.
Other side effects:
Gastroparesis (Stomach “paralisys”)
Mild tachycardia (increased heart rate).
Infections.
Headaches.
Indigestion (upset stomach).
Bowel obstruction
Dumping syndrome
Injection site:
Mild itchiness
changes in skin color, redness, discoloration
Rare side effects:
Pancreatitis.
Medullary thyroid cancer.
Acute (sudden) kidney injury.
Worsening diabetes-related retinopathy.
Who Should Consider GLP-1 Agonists for Obesity?
Individuals with a BMI of 30 or higher: This class of medication is primarily intended for those classified as obese.
Patients with a BMI of 27 or higher and weight-related health conditions: This treatment may benefit those with conditions like type 2 diabetes, hypertension, or dyslipidemia.
For people who have struggled with other weight loss methods, GLP-1 agonists can be an option for those who haven't had success with diet, exercise, or other medications.
Patients who want medications since they are fearfull of weight loss surgery, even if the latter has proven to have better and long lasting results.
Patients whose obesity is so severe they need both tools (medications and surgery)to achieve the best possible results.
Patients who had weight loss surgery and suffer weight regain.
Contraindications for the use of GLP-1 medications
Personal or family history of medullary thyroid carcinoma (MTC)
History of pancreatitis
Severe gastrointestinal disease
Diabetic retinopathy
Gastroparesis
Pregnancy
Treatment Details for Antiobesity medications
How often do you take GLP-1 agonists?
Most of these medications are administered through subcutaneous injection (abdomen or thigh)
The frequencies of the injections are:
Semaglutide: Once a week.some text
Dosage forms:
injection, prefilled, single-dose pen (Ozempic)
2mg/1.5mL (1.34mg/mL); delivers doses of 0.25mg or 0.5mg per injection
Following weeks 0.6mg increase per week until reaching 3mg maximum dose.
Tirzepatide: Once a week.some text
Initial four weeks 2.5 mg
Week 5 possible increase to 5mg
Not more than 2.5mg increase per month
Maximum dosage 15mg
Oral semagultide (Rybelsus®): dailysome text
Initial month 3mg for a month
Month 2: 7mg
Month 3: possible increase to 14mg (maximum dose)
Dulaglutide: Once a week.
Exenatide: Twice a day.
Exenatide extended-release: Once a week.
Lixisenatide: Once a day.
*Oral Semaglutide is marketed in three strengths: 3mg, 7mg, and 14 mg. The subcutaneous injection of Semaglutide is available in four strengths: 0.25mg, 0.5mg, 1mg, and 2mg.
*Switching between Ozempic (SC) and Rybelsus (PO)
Oral to SC: Taking 14 mg/day PO: Transition to 0.5 mg SC qWeek on day after last PO dose
SC to Oral: Taking 0.5 mg/week SC: Transition to 7mg or 14 mg PO starting up to 7 days after last SC injection
There is no equivalent PO dose for the 1-mg SC dose
*To date, the FDA has approved three GLP-1, agonists for type 2 diabetes and obesity: liraglutide, semaglutide, and tirzepatide.
Anti-obesity Medication trial results:
Semaglutide - SELECT TRIAL= showed a reduction in BMI of approximately 15%, and HbA1C of 1.9 points
Tirzepatide (SURPASS TRIAL) = showed a reduction in BMI of approximately 20%, and HbA1C of 2.2 points
Comparison with Other Weight Loss Medications
Over decades, several medications have been developed and approved, and some have been retired from the market due to their adverse and detrimental effects. Here is a brief timeline. Results on these medications are behind the ones achieved with GLP-1 by a considerable gap.
OTHER NON-GLP-1 FDA APPROVED ANTI-OBESITY MEDICATIONS:
Phentermine (Adipex®, Lonamin®)
Phentermine/Topiramate (Qsymia®)
Bupropion/Naltrexone (Contrave®)
Orlistat (Xenical®)
IMPACT OF GLP-1 AGONISTS IN THE US:
Approximately 15% of the population has used them
50% know someone who has used them
70%considers it very expensive
The Kardashian effect increased the medication's popularity
States where it is supposedly more used: Louisiana, Florida, and Texas
RELEVANT ASPECTS TO KEEP IN MIND WHEN CONSIDERING GLP-1 AGONISTS
HIGHLIGHTS
The effect of the medication is dependent on the dose.
Weight gain after stopping the medication is a reality.
Not everyone will tolerate the medication or have adequate results with this treatment option.
We live in a "global society" in which we are used to having everything fast, efficiently, and at the reach of a click, so we might unconsciously believe that these medications will act the same way when a person's health and quality of life are in the line things can and should not be fast or easy, at least not if you want to avoid complications or negative consequences.
One who believes that obesity or diabetes problems will be solved with an injection alone or surgery is misinterpreting very good tools to treat these diseases.
Weight regain is a reality with weight loss surgery and anti-obesity medications, which is why it is crucial to do things correctly. We will go deeper into that in the following paragraphs.
Conclusion
Obesity is a complex condition. Effective management often requires management with mutiple therapies, such as:
Dietary changes.
Exercise.
Medications.
Behavior modification programs.
Bariatric (weight loss) surgery.
Comprehensive examination of health status
Close follow-up and guidance by a multidisciplinary team of experts
With these medications, just as with weight loss surgery, the bias in which people think or assume that lifestyle changes, guidance, and follow-up are not necessary, I stand corrected; they are "not necessary"; they are crucial for long-term success and to avoid complications. Neither surgery nor medications are innocuous, so they need to be performed/administered in a multidisciplinary setting with close and prolonged follow-up.
The idea that the advent of anti-obesity medications means the end of bariatric surgery is false since no single treatment method works well for all patients. There will indeed be people for whom surgery is no longer indicated or desired because their treatment goals will be met with medications, but other people would not find them effective, have them available, or tolerate their secondary effects. Some others might need to undergo both medications and surgery to achieve the best outcome.
Even if medications seem to be the solution for everyone, several things need to be kept in consideration; one of the most relevant is the substantial cost of these medications and the fact that the patient needs to take them for months or even years if they wish to continue getting sustainable results something that with surgery is not as difficult when the patient does proper Lifestyle Changes. This concept, of course, is very similar to other medications used for other chronic diseases such as high blood pressure and cholesterol, in which the medication needs to be used permanently to have the clinical benefits since they do not persist when the medication is ceased.
Besides availability, cost will be the main barrier when scarcity ends since the medication not only has to be prescribed for years but also usually needs to be increased in dosage.
GLP-1 agonists offer a promising solution for individuals struggling with obesity, especially when combined with lifestyle changes. While they aren't a magic bullet and come with their own set of challenges, the benefits of weight loss and improved metabolic health make them an attractive option for many. As with any medication, it's crucial to consult bariátrica surgeon to determine if GLP-1 agonists are the right choice. With the scarcity of branded semaglutide and tirzepatide and the availability of peptides that mimic the GLP-1's, my concern is that many patients have access to treatment without any supervision; this is very dangerous since it is not just a matter of getting the "skinny shot" and you're done! It requires a comprehensive evaluation and guidance to avoid complications, side effects, or adverse effects, which not many places mention, such as muscle and bone mass loss (sarcopenia and osteopenia), which leads to even more health problems.
If you're interested in learning more about GLP-1 agonists or exploring treatment options for obesity, contact us, and we will determine whether it is a good fit for you.
%2016.56.30.png)
