Just How Effective Are These Injectable Weight Loss Medications?

Literature Sources

1) "Weight Loss Outcomes Among Early High Responders to Exenatide Treatment: A Randomized, Placebo Controlled Study in Overweight and Obese Women" (2021) by Megan Rodgers and others. Link to Article.
2) "A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management" (2015) by Xavier Pi-Sunyer and others. Link to Article.
3) "Effect of Weekly Subcutaneous Semaglutide vs Daily Liraglutide on Body Weight in Adults With Overweight or Obesity Without Diabetes: The STEP 8 Randomized Clinical Trial" (2022) by Domenica M Rubino and others. Link to Article.
4) "Tirzepatide for Weight Reduction in Chinese Adults With Obesity: The SURMOUNT-CN Randomized Clinical Trial" (2024) by Lin Zhao and others. Link to Article.
5) "Tirzepatide 10 and 15 mg versus semaglutide 2.4 mg in people with obesity or overweight with type 2 diabetes: An indirect treatment comparison" (2025) by Emily R Hankosky and others. Link to Article.
6) "Adverse Effects of GLP-1 Receptor Agonists" (2015) by Theodosios D Filippatos and others. Link to Article.
6) "Weight regain and cardiometabolic effects after withdrawal of semaglutide: The STEP 1 trial extension" (2022) by John P H Wilding and others. Link to Article.

Scientists first discovered a chemical found in the saliva of an animal called the gila monster, pictured above. They noticed this chemical imitated hormones produced naturally in humans to regulate food metabolism by stimulating insulin release and decreasing appetite, which could be especially useful for those with diabetes mellitus type 2. So they extracted it from the animal, concentrated it, and sold it as an injectable medication called exenatide, which was the first in a new class of medications called glucagon-like-peptide 1 (GLP-1) agonists.

Initially used to treat diabetes, observers noticed that a major side effect of the drug was weight loss, significant in some cases. For example, in study #1, researchers noticed that 56% of patients injecting exenatide 10 mcg daily (likely 5mcg twice daily), which is a therapeutic dose for diabetes management, lost more than 5% of their weight over the 52-week study period. In the same study, 23% of patients lost more than 10%.

Over the years, pharmaceutical companies developed newer medications similar to exenatide, but with small structural changes that made them easier to use for long term therapy. Liraglutide could be dosed at one time per day, instead of twice daily like with exenatide. Semaglutide extended that dosing period to one time per week. Tirzepatide was similarly dosed at one time per week, but it has an additional biological pathway that stimulates fat metabolism better than pure GLP-1 agonists like semaglutide.

Further studies highlighted the fact that weight loss is a major effect from this class of medications. Scientists did an experiment (study #2) with liraglutide over a 56-week period. Patients were either assigned a placebo or the medication, liraglutide 3mg, and told to inject it once daily. At the end of the study, about 63% of the patients lost more than 5% of their weight and 33% of patients lost more than 10%. These results were statistically significant when comparing liraglutide to placebo where 27% of patients lost more than 5%, and 10% more than 10% of their weight. Important to note, is that in this study, patients had to be obese or overweight with concurrent comorbidities to qualify, thus these results may be very different in those who are already healthy and in shape.

In another study (study #3), researchers compared liraglutide to the newer GLP-1 agonist, semaglutide, via dual double blinded placebo controlled study. In the first arm, patients either received semaglutide 2.4mg once weekly (or 1.7mg if unable to tolerate the side effects) or a placebo injection. In the second arm, patients either received liraglutide 3mg daily or a placebo injection. The study lasted for 68 weeks. At the end, researchers noticed about 25% of patients in the liraglutide arm of the study lost more than 10% of their body weight, however, in the semaglutide arm, over 70% of patients lost more than 10% of body weight and about 38% of patients lost over 20% of body weight.

When comparing semaglutide to tirzepatide, both seem to offer similar reductions in weight when used at appropriate doses. Researchers in study #4 compared tirzepatide 15mg once weekly injection to a placebo injection over 52 weeks. At the end of the study, about 72% of the patients lost more than 10% of their body weight. Tirzepatide does seem to provide a better overall metabolic profile when used in overweight patients who have diabetes. In one observational study (study #5), scientists compared data found in clinical trials and noticed that when compared to semaglutide, tirzepatide 15mg improved/reduced hemoglobin A1c 0.56% more when it is used in patients with diabetes mellitus type 2.

It All Sounds Too Good. What Is The Catch?

These medications have opened a new door for many people who find it difficult to lose weight via just diet and exercise, but there are some things to consider before starting on them.

The best results (highest weight loss) will occur in people who have the most to lose. Most clinical trials on this type of medication look only at overweight people, therefore it is not really known how well these medications will work in people with a BMI < 26. It is also well known that the less body fat you have, the harder it will be to lose that fat, so a large weight reduction is not expected in slender and athletic people taking GLP-1 agonists.

GLP-1 agonists are not side effect free. Those taking them are at an increase risk of having diarrhea, constipation, nausea, vomiting, bloating, gastroenteritis and fatigue. There have been concerns regarding an increased risk of pancreatitis and medullary thyroid cancer based on research on animals, but those risks have not been conclusively replicated in human studies. Nevertheless, it is generally recommended to avoid these drugs if you have a family history of medullary thyroid cancer or a history of pancreatitis.

The biggest caveat regarding using these medications for weight loss is that they only work while you are taking them. In study #6, scientists followed patients for a year after finishing treatment with a GLP-1 medication, and noticed that the average weight regain was about 67% of the weight lost during treatment. They stopped the follow-up at one year, but it is likely that the weight gain would have continued. This is because to maintain weight loss, a permanent lifestyle change must be done to reduce calorie consumption based on your new size. When you stop taking the medication, the urge to eat more reemerges and unless you stop yourself from eating, you will regain the weight.

As more agents emerge with novel ways to help fight off fat gain, it is important to remember that these medications are tools and not crutches. They can aid in the goal to become a healthier person, but that journey must be aided with exercise, healthy food choices and permanent positive lifestyle changes.

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