How GLP-1 medications work for weight loss and what studies say about safety

Key points:

1. Researchers conducted decades of research on the safety and efficacy of GLP-1 use for diabetes patients. Studies on non-diabetic GLP-1 patients are newer and ongoing.
2. People with gastrointestinal medical problems, eye conditions, and specific thyroid tumors are at the most significant risk for adverse effects. Still, the research on these risks is not definitive.
3. Always talk to your provider about your health history and risks before and while taking these weight loss drugs and report any new or changing side effects or symptoms.

At Dr. B, we believe your health and longevity should never come at the expense of your safety. That’s especially true when it comes to the medications we prescribe.

So we had a team of medical professionals craft every treatment step for our holistic prescription weight loss program, Shed It. And we pay extra attention to updated studies on the complex effects of GLP-1s.

To help you stay informed, we’ll first review clinical trials that helped the FDA approve popular GLP-1 medications. Then, highlight safety risks that remain unknown.

What studies show about GLP-1 efficacy

GLP-1 agonist medications mimic glucagon-like peptide-1 (GLP-1), a hormone secreted by the gut when we eat.

GLP-1 encourages the production of insulin, which helps lower blood sugar levels that increase after eating certain foods. GLP-1 also slows the rate at which food leaves the stomach, which can help us feel full for longer. And because we have GLP-1 receptors in our brains, the medications can reduce general hunger and food noise.

Altogether, these factors help patients on GLP-1 medications decrease calorie consumption and lose weight.

GLP-1 weight loss medications include Liraglutide (Saxenda®*), Semaglutide (Wegovy®*), and Tirzepatide (Zepbound®*).

Liraglutide (Saxenda®)

Liraglutide is the active ingredient in Saxenda® (for weight loss) and Victoza®* (for diabetes). These brand-name medications come as autoinjector pens.

Before receiving FDA approval, Sexenda® underwent 3 Phase III clinical trials that included

 over 5,000 patients who participated for 56 weeks. By the trial’s end, over 60% of participants had lost at least 5% of their starting body weight, over 30% lost at least 10% of their starting body weight, and about 6% lost at least 20% of their starting body weight.

In an additional 3-year trial, patients received either Saxenda® or a placebo and underwent a lifestyle modification program that included a reduced-calorie diet and physical activity counseling. Of those who completed the trial, 52% of patients had retained a weight loss of at least 5% at the 3-year mark.

Additionally, some patients may take compounded injectable Liraglutide, which comes in vials and is drawn into a syringe. Compounded forms are not included in clinical testing for FDA approval. But at comparable doses, compounded and brand-name Liraglutide medications produce similar results.

Semaglutide (Wegovy®)

Semaglutide is the active ingredient in Wegovy® (for weight loss) and Ozempic®* (for diabetes), both of which are available in auto-injector pens.

To obtain FDA approval, 4,000 patients participated in four randomized, double-blind, placebo-controlled trials lasting 68 weeks. (Double-blind means neither the participants nor the researchers knew which patients received medication and which received placebos.) In the end, those who took Wegovy® lost an average of 12.4% of their starting body weight compared to those who took a placebo.

Some patients may take a compounded oral form of Semaglutide via sublingual administration. Oral forms absorb differently in the body than injectable forms. And compounded medications do not undergo clinical studies. So while compounded sublingual medications contain the same active ingredient (Semaglutide), we have limited clinical information about their safety and efficacy.

Tirzepatide (Zepbound®)

Tirzepatide is the active ingredient in Zepbound® (for weight loss) and Mounjaro® (for diabetes), both of which are available as auto-injector pens. Additionally, LillyDirect supplies patients without insurance an affordable form of *Zepbound in vials pre-filled with their prescribed dosage.

In two randomized, double-blind, placebo-controlled trials, 3,000 patients with a BMI above 27 received a weekly injection of a placebo or Zepbound®. They also all followed dietary and fitness counseling for 72 weeks. In the end, those who took Zepbound® lost up to 20.9% of their starting body weight! Those on placebos lost 3.9%.

Potential risks of GLP-1s

While GLP-1 medications have been around as diabetes medications for decades, they’ve only been available as weight loss treatments for non-diabetic people for a few years. As diabetes can affect many areas of the body, we’re still learning how GLP-1 treatment affects individuals without diabetes.

Newer studies, analyses, and anecdotal evidence (on FDA-approved medications) are providing updated information. But to stay safe, report your health history and any new or changing symptoms to your provider.

Here are a few possible risks to consider.

Thyroid tumors

GLP-1 medications have caused thyroid C-cell tumors to grow in rats and mice. We don’t have proof they do the same in humans—but we only have four or so years of studies to work from. So if you have a family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2), talk to your provider about this possibility.

Eye conditions

Clinical trials and anecdotal data suggest that GLP-1 medications may increase the risk of eye conditions like diabetic retinopathy (damage to the retina), blindness and strokes of the optic nerve. Current studies on non-diabetic patients are ongoing—and their results sometimes conflict. Still, talk to your provider about these risks if you have a history of any eye medical condition—especially if you have any history of diabetes or blood sugar issues.

Pregnancy and birth

In animal trials, some animals treated with GLP-1s had higher rates of miscarriage or bore offspring that were smaller or had more congenital disorders than expected. But the effect of GLP-1 prescription weight loss medications on human fetuses is unknown. We also don’t know if they pass through breast milk—or what happens to infants if they do.

Analyses published in the last year do not show an increased risk of miscarriage or congenital disorders. But we still don’t have clinical trials to confirm an absence of risk. (And the results could be disastrous if there is a risk!) So experts recommend stopping GLP-1 treatment two months before any pregnancy and not taking GLP-1 medications while breastfeeding.

Increased pregnancy with oral birth control

Because of slowed digestion, studies suggest that a 5mg dose of Tirzepatide (Zepbound®/Mounjaro®) decreases the absorption of oral birth control methods by 20%. (They did not find the same of Semaglutide, Liraglutide or Dulaglutide.) Health experts recommend doubling up with barrier birth control or switching to a non-oral method while on this GLP-1 long-term.

Pancreas and intestinal disease

In clinical trials on patients with diabetes, GLP-1 medications increased the risk of pancreatitis (chronic inflammation of the pancreas), gastroparesis (a condition that affects stomach muscle movement) and bowel obstruction.

However, since their approval as a weight loss treatment, newer study results conflict about this risk. Some suggest a slight increase in pancreatitis, bowel obstruction and pancreatitis risk. Others show that GLP-1 treatment reduces pancreatitis risk—even if you have a history of pancreatitis!

Gastrointestinal side effects including nausea and cramping are the most common for those on GLP-1 prescription drugs. Especially if you have a history of GI health conditions, talk to your provider. You’ll want to know what to watch for and if side effects signify a budding condition.

For details, head to the Shed It article, How to anticipate and tackle GLP-1 medication side effects.

Are compounded GLP-1 medications safe?

Pharmacists at specialized pharmacies make compounded medications to address drug shortages or fit a patient’s specific needs.

In Shed It, Dr. B offers compounded injectable Liraglutide and compounded sublingual Semaglutide from licensed pharmacies. These pharmacies follow strict safety standards and test their products for quality, potency, stability and effectiveness.

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*Byetta®, Saxenda®, Victoza®, Wegovy®, Ozempic®, Trulicity®, Zepbound® and Mounjaro® are registered trademarks of their respective owners. Our use of these names is for informational purposes only and does not imply any affiliation, endorsement or approval by the trademark holders.

Sources:

Biopharma PEG. (2022). Evolution of GLP‐1 Receptor Agonists for Diabetes Treatment.

Cai, C.X., et al. (2025). Semaglutide and Nonarteritic Anterior Ischemic Optic Neuropathy. JAMA Ophthalmology.

Drucker, D. J., et al. (2017). Discovery, characterization, and clinical development of the glucagon-like peptides. The Journal of Clinical Investigation.

Friedman, J. M. (2024). The discovery and development of GLP-1 based drugs that have revolutionized the treatment of obesity. Proceedings of the National Academy of Sciences.

Hathaway, J.T. et al. (2024.) Risk of Nonarteritic Anterior Ischemic Optic Neuropathy in Patients Prescribed Semaglutide. JAMA Ophthalmology.

Lilly/Zepbound. (2024). Clinical data. Healthcare providers.

Madsen, L. et al. (2012). GP1 Receptor Agonists and the Thyroid: C-Cell Effects in Mice Are Mediated via the GLP-1 Receptor and not Associated with RET Activation. Endocrinology.

Sodhi, M,. et al. (2023). Risk of gastrointestinal adverse events associated with glucagon-like peptide-1 receptor agonists for weight loss. JAMA.

US Food and Drug Administration. (2024). Compounding and the FDA: Questions and answers.

US Food and Drug Administration. (2021). FDA approves new drug treatment for chronic weight management, first since 2014.