What Is GLP-1? How GLP-1 Medications Work and Their Risks

GLP-1 (glucagon-like peptide-1) is a natural hormone your gut releases after a meal. It signals fullness to your brain, prompts your pancreas to release insulin and slows how quickly your stomach empties. GLP-1 medications are man-made versions of it, used to treat type 2 diabetes and, in some people with obesity, for weight loss.^[1]

Key takeaways

• Semaglutide acts on the GLP-1 receptor alone, while tirzepatide acts on both the GIP and GLP-1 receptors, so the two are related but not identical.
• Both injections start at a low dose and step up; the semaglutide label says this is to reduce the risk of stomach side effects.
• In clinical trials of semaglutide, weight changes were group averages with lifestyle support, so individual results may vary.

What is GLP-1 and how do GLP-1 medications work?

GLP-1 stands for glucagon-like peptide-1. Medications in this class are called GLP-1 agonists: synthetic hormones that cause many of the same actions as the natural one and enhance those processes in the body. MedlinePlus puts it simply: "The higher the dose, the more the effect."^[1]

Semaglutide and tirzepatide are two medicines that act on the GLP-1 receptor, each given as a once-weekly injection under the skin.^[3][4] As a class, GLP-1 agonists are used to treat type 2 diabetes, and some are used for weight loss in people with obesity.

Stomach side effects such as nausea, vomiting and diarrhea are the most common problems, and people with a personal or family history of medullary thyroid carcinoma or MEN 2 should not use these medicines; the safety section below has the details.^[2][2]

For a closer look at one of these medicines, see our semaglutide injections guide on dosing, safety and who qualifies.

Semaglutide vs tirzepatide: how do these GLP-1 medications differ?

Semaglutide is a GLP-1 receptor agonist. Its label tells prescribers to start low and follow a dose-escalation table, which is done to reduce the risk of stomach side effects.^[3] Semaglutide also comes as a tablet. If you want the dose steps and syringe units for the injection, our semaglutide weight loss dosage chart has them.

Tirzepatide works differently. It acts on both the GIP receptor and the GLP-1 receptor, which makes it a dual agonist rather than a GLP-1-only medicine.^[4] Its label also says the starting dose is for treatment initiation and is not a maintenance dose, so tirzepatide follows a step-up schedule too.^[4]

Which one fits a person depends on their health history, and that is a prescriber's decision.

How much weight do people lose on semaglutide? What trials found

The STEP trials of semaglutide enrolled adults with overweight or obesity. In STEP 1, adults without diabetes took semaglutide 2.4 mg once weekly or placebo, and both groups received a lifestyle intervention.

In that trial, 86.4% of people on semaglutide lost 5% or more of their body weight, compared with 31.5% on placebo, and 69.1% lost 10% or more, compared with 12.0%.^[5] These are group averages, so individual results may vary.

STEP 5 followed 304 adults with obesity, or with overweight and at least one weight-related condition, none of whom had diabetes. At week 104, mean weight change was −15.2% with semaglutide 2.4 mg and −2.6% with placebo, both alongside behavioral support.^[6]

These figures describe semaglutide in trial participants, and they say nothing about how tirzepatide compares. Because both groups also had lifestyle support, what you eat still matters; our GLP-1 diet guide covers that.

GLP-1 side effects and safety: what the labels say

The details below come from the FDA labels for semaglutide 2.4 mg injection and for tirzepatide. Talk to a licensed clinician about which of these warnings apply to you.

Boxed warning and who should not use these medicines

Both carry a boxed warning about thyroid C-cell tumors:

• Semaglutide: in rodents it causes thyroid C-cell tumors that depend on dose and treatment duration, at clinically relevant exposures; whether it does so in humans, including causing medullary thyroid carcinoma (MTC), is unknown.^[3]
• Tirzepatide: in rats it causes thyroid C-cell tumors; whether it does so in humans, including causing medullary thyroid carcinoma (MTC), is unknown.^[4]

Tirzepatide^[4] and semaglutide should not be used by anyone with a personal or family history of MTC or MEN 2.^[3] Tirzepatide^[4] and semaglutide should not be used if you have had a serious allergic reaction to the medicine or its ingredients.^[3]

Common side effects

In the pooled trials in the original semaglutide 2.4 mg label, 73% of treated patients reported gastrointestinal disorders, versus 47% on placebo. Nausea was reported by 44% versus 16%, vomiting by 25% versus 6% and diarrhea by 30% versus 16%.^[2] Rates in newer labels may differ.

Stopping treatment because of side effects was less common: nausea led 1.8% of treated patients to stop (0.2% on placebo), vomiting 1.2% (0%) and diarrhea 0.7% (0.1%).^[2] Constipation, abdominal pain, headache, fatigue and indigestion were also reported in at least 5% of patients.^[2]

Other warnings on the semaglutide label

• Pancreatitis: acute pancreatitis has been observed with GLP-1 medicines, so treatment should be stopped if it is suspected; watch for persistent severe abdominal pain, sometimes spreading to the back, with or without vomiting.^[3]
• Gallbladder disease: it has occurred in clinical trials, and suspected gallstones call for gallbladder tests and follow-up.^[3]
• Low blood sugar: using it with insulin or a sulfonylurea may raise the risk of severe hypoglycemia, so those doses may need to be reduced.^[3]
• Kidney injury and dehydration: kidney function should be monitored in people with side effects that could cause fluid loss.^[3]
• Severe stomach problems: it is not recommended in people with severe gastroparesis.^[3]
• Allergic reactions: anaphylaxis and angioedema have been reported, and you should seek medical advice promptly if they are suspected.^[3]
• Diabetic retinopathy: complications have been reported in trials in people with type 2 diabetes, so those with a history of it should be monitored.^[3]
• Heart rate: in weight-reduction trials, resting heart rate rose by a mean of 1 to 4 beats per minute compared with placebo, and palpitations or a racing heartbeat at rest should be reported.^[3]
• Mood: a suicidal behavior and ideation warning that appeared in earlier labels was removed in the February 2026 revision; tell your provider about any mood changes.^[3]

Other warnings on the tirzepatide label

Tirzepatide's label warns of severe gastrointestinal reactions and says it is not recommended in severe gastroparesis.^[4] It also warns of acute kidney injury from fluid loss, and using it with insulin or an insulin secretagogue may increase the risk of hypoglycemia.^[4]

Before starting any GLP-1 medicine, tell a licensed clinician about: thyroid cancer in your family; past pancreas or gallbladder problems; your diabetes medicines; and any planned procedures. Pulmonary aspiration has been reported in people taking GLP-1 receptor agonists who had elective procedures under general anesthesia or deep sedation, and semaglutide delays gastric emptying, which may affect how well oral medicines taken at the same time are absorbed.^[3]

Getting semaglutide injections through ShopMedRx

ShopMedRx offers semaglutide as a once-weekly subcutaneous injection you take at home. The current price is $149 every 4 weeks, with $0 membership fees, and because we do not bill insurance, you pay cash. The page also shows a microdosing option, a lower weekly dose, and a clinician decides whether either dosing approach is appropriate for you.

1. You complete a short online health assessment.
2. A licensed clinician in your state reviews it and prescribes only if it is clinically appropriate. A prescription is not guaranteed, and if you are not prescribed, you are not charged.
3. If your prescription is for a compounded medication, a state-licensed 503A compounding pharmacy prepares it and it ships to you in unmarked packaging. Other prescriptions are filled by a licensed U.S. pharmacy.

Some medications we offer are compounded. We partner with state-licensed 503A compounding pharmacies and do not manufacture them. Compounded medications are not FDA-approved, and the FDA does not review compounded drugs for safety, effectiveness or quality.^[7]

We also offer tirzepatide injections and oral semaglutide. Details on the injection are on our semaglutide injections page.

If you're considering treatment, you can check if you qualify online.

Bottom line

GLP-1 medications mimic a natural fullness hormone, and semaglutide and tirzepatide are two of them, each with its own step-up dosing and safety limits. If you want to know whether one could be right for you, the next step is a short online assessment that a clinician in your state reviews.

Frequently asked questions

Can you use two GLP-1 medications together?

No. The semaglutide label says that using it with other semaglutide-containing products or any other GLP-1 receptor agonist is not recommended.^[3] Tirzepatide's label gives the same advice about combining it with any GLP-1 receptor agonist.^[4]

Do I need a prescription for GLP-1 medications?

Yes. The FDA advises patients to get a prescription from their doctor and fill it at a state-licensed pharmacy.^[7] Skipped screening and no prescription from a licensed doctor are red flags with telehealth sellers.^[7] At ShopMedRx, a licensed clinician in your state reviews your assessment and prescribes only if it is clinically appropriate.

Can I use HSA or FSA funds for semaglutide injections?

Our products are HSA/FSA reimbursable, as shown on the product pages, but we do not bill insurance, so check with your plan about what it will pay. To request what you need to claim reimbursement, email support@intake.shopmedrx.com.

Talk to a licensed clinician

Before you start, stop or change any GLP-1 medicine, talk to a licensed clinician about your health history and other medicines. If you'd like to see whether semaglutide injections from ShopMedRx could be appropriate for you, you can check if you qualify.

Important information

• This article is for general education and is not medical advice. Talk to a licensed clinician before starting, stopping or changing any treatment.
• All medications available through ShopMedRx are prescription only and are prescribed only if appropriate after a licensed clinician's review.
• Some medications we offer are compounded. Compounded medications are not FDA-approved, and the FDA does not review compounded drugs for safety, effectiveness or quality before they are marketed. They are not the same as, or generic versions of, brand-name drugs.
• Individual results may vary. Nothing in this article promises a specific result.
• Prescriptions are written by clinicians licensed in the patient's state (through OpenLoop Health), only when clinically appropriate. Compounded medications are prepared by state-licensed 503A compounding pharmacies; ShopMedRx does not manufacture compounded medications. Other prescriptions are filled by licensed U.S. pharmacies.

Sources

1. MedlinePlus. GLP-1 agonists. National Library of Medicine (NIH). https://medlineplus.gov/ency/article/007853.htm
2. U.S. Food and Drug Administration. Semaglutide injection 2.4 mg: prescribing information (original 2021 label). U.S. FDA, 2021. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/215256s000lbl.pdf
3. U.S. Food and Drug Administration. Semaglutide injection and tablets: prescribing information. DailyMed, National Library of Medicine (current label). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ee06186f-2aa3-4990-a760-757579d8f77b
4. U.S. Food and Drug Administration. Tirzepatide injection: prescribing information (2026 label). U.S. FDA, 2026. https://www.accessdata.fda.gov/drugsatfda_docs/label/2026/217806s002lbl.pdf
5. Wilding JPH, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine, 2021. https://www.nejm.org/doi/full/10.1056/NEJMoa2032183
6. Garvey WT, et al. Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial. Nature Medicine (via PMC). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9556320/
7. U.S. Food and Drug Administration. FDA's Concerns with Unapproved GLP-1 Drugs Used for Weight Loss. U.S. FDA. https://www.fda.gov/drugs/drug-alerts-and-statements/fdas-concerns-unapproved-glp-1-drugs-used-weight-loss