Background: The Science and Evolution of AOMs

Our background section dives into the science underlying AOM effectiveness. We share the molecules that form the core of these medications and offer insights into how they work. Additionally, we outline the history of AOMs, highlighting key milestones in their development and approval.

Molecule History and Use Cases of GLP-1

The scientific breakthrough of Anti-Obesity Medications (AOMs) traces back to the 1980s discovery of a hormone called the glucagon-like peptide 1 (GLP-1) (Park, 2015). GLP-1 responds to food intake and plays a crucial role in regulating blood sugar (glucose) levels and reducing appetite (Surampudi, 2023). This hormone's discovery opened new avenues in medical treatments, particularly in Type 2 Diabetes and Weight Loss.

Type 2 Diabetes: GLP-1 quickly garnered attention for its potential in treating Type 2 diabetes. By causing the body to create more insulin, it helps lower blood sugar levels effectively (Knudsen & Lau, 2019). Over the years, GLP-1-based treatments have become a cornerstone in managing Type 2 diabetes, with several medications gaining prominence for their dual benefits on glycemic control and body weight regulation (Knudsen & Lau, 2019).

Weight Loss: Subsequent research has also shown that higher levels of GLP-1 can interact with brain receptors, leading to reduced appetite and increased feelings of fullness (Surampudi, 2023). This breakthrough led to the development of GLP-1 medications specifically targeting weight loss and weight management. Clinical trials prove that GLP-1s lead to significant weight loss results when used together with diet and exercise, marking a new era in obesity treatment.

Treating a Chronic Health Disease with Anti-Obesity Medications

Obesity, a complex health challenge, is when a person’s weight is higher than what is considered healthy for a given height (NIDDK, 2021) (Wilding et al., 2021). Body Mass Index (BMI) is categorized into ranges:

• Underweight: <18.5 BMI

• Healthy weight: 18.5 to <25 BMI

• Overweight: 25.0 to <30 BMI

• Obesity: 30.0 or higher BMI

• Severe obesity: 40 or higher BMI

Recent data indicated that 42.4% of adults in the U.S. suffer from obesity, with 9.2% experiencing severe obesity (Overweight & Obesity Statistics - NIDDK 2021). Alarmingly, nearly 1 in 5 children and adolescents are obese, with 6.1% classified as severely obese. Obesity is not just about weight; it significantly increases the risk of various health issues like insulin resistance, high blood pressure, cardiovascular disease, Type 2 diabetes, and some cancers.

Acknowledging these risks, obesity is a chronic disease and a global health challenge (Wilding et al., 2021). It requires ongoing management and can often lead to other chronic conditions, underscoring the need for effective treatment strategies (Castro, 2022).

In this context, Anti-Obesity Medications (AOMs) have emerged as a vital component in combating obesity. These medications work by targeting various mechanisms like appetite suppression and metabolism enhancement, aiding in weight loss and its maintenance (Surampudi, 2023). While AOMs have shown promise, it's important to note that they are most effective when used as a piece of treatment strategy, which includes lifestyle modifications like diet and exercise, and sometimes psychological support (Surampudi, 2023).

Popular FDA-Approved Medications and Method of Use

The most common and FDA-approved GLP-1 agonist drugs for weight loss, including their brand name, dose, and FDA approval years, are as follows:

• Semaglutide (Wegovy) (Castro, 2022)

• Dosage: 2.4 mg injection once weekly.

• FDA Approval: 2021

• Tirzepatide (Zepbound) (FDA, 2023)

• Dosage: injection once weekly. Starts with 5 mg weekly for the first week, then gradually to 10 mg or 15 mg one time per week after four to twenty weeks.

• FDA Approval: 2023

• Liraglutide (Saxenda) (Castro, 2022)

• Dosage: injection once daily. Begins with 0.6 mg daily during the first week, then gradually increasing to 3.0 mg daily starting from week 5

• FDA Approval: originally approved in 2014 with a supplemental approval in 2020

As of January 2024, the FDA has not approved generic versions of GLP-1 drugs (FDA, 2024).

For detailed information about these approved medications, including their effectiveness, safety profile, and company information, refer to the “Brands” section below.

Trends in Taking GLP-1s

Given the popularity and effectiveness of GLP-1s, coupled with both the high costs and the supply chain struggling to keep up with demand, several new companies have entered the market and accelerated the following trends related to how to take the medications:

1. Low dose: instead of taking the full dose recommended by the brands, some patients are taking the medication in smaller doses consistently over time in an attempt to lose weight. A few reasons underlying this trend could be the original FDA approval for Type 2 diabetes treatments, the typical starting point for weight loss medication treatments, and dosing strategies as a result of supply chain challenges (Han et al., 2023). For Type 2 diabetes treatment, providers initially prescribed Semaglutide (“Ozempic'' brand name) in conjunction with diet and exercise programs at doses of up to 1 mg weekly. At this dosage, the clinical trials indicated weight loss for Type 2 diabetes patients. For semaglutide prescribed for weight loss in patients who have obesity, the studied and approved dosage is 2.4mg per week after increasing to this amount gradually over 16 to 20 weeks to reduce the gastrointestinal side effects (FDA, 2021). The results of the largest clinical trial for Wegovy included 16 weeks of dose increases, and after 68 weeks of taking Wegovy the average body weight loss was 12.4%. These results indicate the effectiveness of the higher dosage, and we cannot find a clinical trial on the effectiveness of sustained lower-dose GLP-1s. As always, this trend may be due to the consultation and prescriptions from licensed healthcare providers for specific treatment plans.

2. Compounded GLP-1s: according to the FDA, when a drug is in shortage, manufacturers can make a compounded version meeting certain FDA requirements (FDA, 2023). A compounded drug is made with a combination of mixed or altered ingredients. Compounded drugs are not fully FDA-approved or vetted for safety or effectiveness. Due to the shortage of GLP-1 drugs, both Ozempic (approved for treating Type 2 Diabetes) and Wegovy (approved for treating obesity) are on the FDA’s shortage list as of May 2023, making compound GLP-1s available (FDA, 2024). The FDA recommends using approved drugs when available instead of a compounded drug. Finally, it is important to be aware of the difference between the compounded GLP-1s and potential counterfeit GLP-1s that are fraudulent, illegally marketed, or blatantly unapproved. Check out the FDA’s site for additional topics on compounded GLP-1s and, as always, consult a licensed healthcare provider for consultation.

3. Oral GLP-1s: there are currently no oral GLP-1s FDA-approved for obesity, however, Rybelsus is an oral GLP-1 approved for type 2 diabetes (Tucker, 2023). This may change in the coming years however as a recent study by Eli Lilly found daily oral use of a nonpeptide GLP-1 receptor agonist called orforglipron associated with weight reduction of at least -10% by week 36 in 46 - 75% of participants (Dunleavy, 2023). These initial results are encouraging and additional clinical trials of pill-form GLP-1 are underway by Novo Nordisk, and Pfizer is also in clinical trials for an oral GLP-1 medication (Pfizer, 2023). Pending trial success, an FDA-approved oral GLP-1 will become available.

Benefits and Effectiveness of GLP-1 Anti-Obesity Medications

GLP-1 Anti-Obesity Medications work because they mimic/spark the reaction of the naturally occurring GLP-1 hormone. The wide range of benefits of GLP-1 includes lowering blood sugar and reducing weight, as well as other benefits such as improving lipid disorders and fatty liver disease, reducing heart disease risk, and delaying diabetes-related nephropathy progression (Cleveland Clinic, 2023). The recently approved medications are focusing on weight loss, however, companies are exploring the range of benefits that the GLP-1 hormone provides for the next evolution of these medications (Cleveland Clinic, 2023).

GLP-1 medication benefits and effectiveness for weight loss vary based on several factors including starting weight, the specific GLP-1 drug used, and the dosage (Castro, 2022).

Strong Results of an Early Study on Semaglutide (Wilding et al., 2021)

• One study on once-weekly semaglutide (2.4 mg) involving 2,000 obese adults showed an average body weight loss of about 15% after 68 weeks.

• The study compared participants on semaglutide in addition to a diet and exercise program to those who only followed the diet and exercise regimen.

• The key findings were as follows:

• Nearly a third of the participants using semaglutide lost 20% of their body weight.

• In contrast, adults only incorporating diet and exercise lost about 2.4% of their body weight.

FDA Study References:

• Wegovy: According to the FDA, people using Wegovy lost 12.4% of their initial body weight on average as compared to people using the placebo (FDA, 2021)

• Zepbound: In a trial for Zepbound, participants on the highest approved dose (15 mg once per week) lost 18% of their body weight on average compared to participants receiving a placebo (Thompson, 2023)

These studies highlight the potential high effectiveness of GLP-1 medications in weight management. However, it's important to note that studies show weight regain recurrence after stopping the medication (Surampudi, 2023). This underscores the importance of lifestyle changes for sustainable weight management, including diet and exercise. Dr. Surampudi emphasizes that while anti-obesity medications are a valuable tool, the fundamentals of weight management remain diet and exercise.

We recommend consulting with a healthcare provider to determine the most appropriate treatment plan, as these medications may not be suitable for everyone and individual results can vary.