As I was ideating for topics to cover this week, I happened to see on my calendar that I had an appointment with a weight loss clinic just days away. This was an appointment I scheduled last year in November, fueled by my frustration at my failed weight loss attempts.
For the last 6 years, my weight has fell under 90kg on just one occasion; my marathon race which I ran at 89kg. As I am only 179cm tall, my BMI has consistently remained in the overweight range. My most recent blood test also indicates that I have borderline hypertension and high cholesterol. After some deliberation, I decided to seek some help.
The reason I made an appointment 3 months in advance, was to give myself some time for a Hail Mary attempt at losing weight on my own, instead of immediately relying on the latest biotechnological breakthroughs (and also many celebratory occasions fall in the December to early February period). Since that hasn’t gone too well, it’s time for me to do some research on alternative ways of losing weight to get healthy.
As a strong advocate of doing your own research before doing anything that might permanently affect your body, I will dedicate this week’s article to my personal research on obesity and how semaglutides actually helps in weight loss.
What are GLP-1 RAs?
GLP-1 Receptor Agonists (GLP-1 RAs) are a type of medication that mimics the action of glucagon-like peptide-1 (GLP-1), which is a hormone that is involved in regulating our blood sugar level, as well as appetite control by promoting satiety through our central nervous systems.1
These drugs were originally developed for type 2 diabetes, but its usage for other purpose has become more prevalent in recent years. Research has also shown its effectiveness in reducing clinically important kidney and cardiovascular events.2
However, it is important to acknowledge that its usage in weight management is still being studied. A key thing to note would be the benefit-harm balance of GLP-1 RAs. Despite its efficacy in achieving weight loss, harmful side effects such as alopecia and vomiting has been reported in rather large amounts.3
Types of GLP-1 RAs
Now that we have an idea of what GLP-1 RAs are, it’s time to look into the types of GLP-1 RAs that are currently available.
Semaglutides
Semaglutides are FDA-approved drugs that are used for chronic weight management and type 2 diabetes.4 It has also shown to reduce cardiovascular risk in patients with obesity and preexisting heart diseases.5
Latest efficacy research data shows that the use of semaglutides in treating non-diabetic obesity has led to a 11.8% mean body weight reduction, as compared to the placebo group, in 68 weeks.6
Some side effects commonly seen in patients being treated with semaglutides are mostly mild or moderate gastrointestinal issues. However, cases of gallbladder disorders and cholelithiasis have been linked to the usage of semaglutides, with its users being 1.26 times and 2.06 times more likely to have face the respective side effect as compared to the placebo group.7
Liraglutides
Liraglutides are GLP-1 RAs that are 97% similar to that found in the human body. Liraglutides has proven to be effective in aiding weight loss. A study done on the clinical effectiveness of liraglutides, applied on 399 people living with obesity over the span of 6 months, has resulted in a mean average weight loss of 6.5kg, with majority losing more than 5% of their body weight.8
Regarding side effects, liraglutides share a lot of similarities to semaglutides, in that a large number of people experiencing gastrointestinal (GI) side effects due to the drug, though mostly at early stages of treatment.9
An interesting statistical difference between liraglutides and semaglutides, lies in a significantly larger percentage of people discontinuing liraglutides (27.6%) as compared to semaglutides (13.5%)10. This might be due to medication fatigue, since liraglutides require daily injections while semaglutides are usually done weekly.
Tirzepatides
Tirzepatides is a dual GIP/GLP-1 RA that outperforms single GLP-1 RAs. The effectiveness of this drug lies in the effects of GIP. GIP enhances insulin sensitivity, promotes fat cell lipid storage and improve lipid metabolism.
The presence of GIP also helps in reducing GLP-1 RAs induced nausea by inhibiting area postrema neurons, which suppresses nausea.11
Comparative Analysis on the effectiveness in curbing obesity
There have been multiple studies done that directly compares the effectiveness of each drug in curbing obesity. Semaglutides, being the one with a longest safety data, seems to be a suitable benchmark for other peptides.
Semaglutides vs Liraglutides
A clinical trial of over 68 weeks was done on adults who were either obese or overweight. Those that received semaglutides achieved a mean body weight reduction of 15.8%, compared to 6.4% with liraglutides.12
Another clinical trial of 52 weeks reported a 13.8% weight loss with semaglutides at 0.4mg dose, compared to 7.8% with liraglutides.13
Semaglutides vs Tirzepatides
In a 40-week trial, tirzepatide at 5mg, 10mg or 15mg has led to a 1.9kg to 5.5kg greater weight loss as compared to semaglutides at 1mg.14 A real-world study has also found that tirzepatides users had a 2.4% to 6.9% greater weight loss at 3-12 months.15
Meta-analyses
A network meta-analysis of trials found that tirzepatides users who received 15mg doses achieved a 17.8% weight loss, as compared to 13.9% for semaglutides at 2.4mg doses and 5.8% for liraglutides at 3.0mg doses.16
Long Term Outcomes
After going through all these clinical research data, it’s pretty easy to guess the long term outcomes and benefits of using these drugs. At 208 weeks, semaglutides led to a mean reduction of 10.2% in body weight, sustained over 4 years in the SELECT trial.17
There were also improvements in HbA1c (a blood test that measures blood sugar levels) by 1.8%, blood pressure by 6.5 mmHg systolic and C-reactive protein (a marker for inflammation and infection in our bodies) by 40%.18
There is also an improvement in the general quality-of-life (QOL), as expected when one goes from being overweight/obese to a normal healthy weight.
Side Effects, a Cause for Concern?
As I went through the papers, I found myself being convinced by the multitude of benefits that the drugs offer. Though at the same time, I struggled to get over the high likelihood of experiencing GI side effects. The good news is that, most of the side effects seem to be temporary and would go away after some time.
A very important thing to note is that the only GLP-1 RA that has the longest safety data would be semaglutides, which is better known by the brand Ozempic or Wegovy. With that said, all of these peptides, regardless of whether its semaglutides, liraglutides or tirzepatides, newer research would always surface and it is important for us to keep updating our own knowledge base and understand both the benefits and risks that it brings.
My Personal Take
As someone who is very risk averse in my decision makings, a low possibility of risk is enough for me to avoid taking it. However, I am well aware of the dangers of being overweight, having high blood pressure and high cholesterol issues at just 27.
With the concerns over my health, I have decided to schedule an appointment with the clinic and see if it’s suitable for me. If you have similar health issues as me, I would highly recommend trying to resolve this without immediately resorting to these medications. But if you have been trying for some time and things just haven’t worked out (and you have some spare cash lying around), it’s time to seek some help.
I will keep you guys posted on this topic if new research surfaces. I also plan to do a short update each week if I do end up starting on any medications. Until then, sign up for my newsletter and stay updated!
1. https://www.nature.com/articles/s41392-024-01931-z
2. https://pubmed.ncbi.nlm.nih.gov/39608381/
3. https://pubmed.ncbi.nlm.nih.gov/38846069/
4. https://pubmed.ncbi.nlm.nih.gov/38016699/
5. https://pubmed.ncbi.nlm.nih.gov/38740993/
6. https://pubmed.ncbi.nlm.nih.gov/38016699/
7. https://pubmed.ncbi.nlm.nih.gov/38923272/
8. https://pubmed.ncbi.nlm.nih.gov/37194338/
9. https://pubmed.ncbi.nlm.nih.gov/28392927/
10. https://pmc.ncbi.nlm.nih.gov/articles/PMC8753508/
11. https://pmc.ncbi.nlm.nih.gov/articles/PMC10697893/figure/Fig1/
12. https://pmc.ncbi.nlm.nih.gov/articles/PMC11400221/
13. https://pubmed.ncbi.nlm.nih.gov/30122305/
14. https://pubmed.ncbi.nlm.nih.gov/34170647/
15. https://pmc.ncbi.nlm.nih.gov/articles/PMC11231910/
16. https://pubmed.ncbi.nlm.nih.gov/39761578/
Zen Yi 