What makes something a GLP-1 medication?
Glucagon-like peptide-1 (GLP-1) is an incretin hormone secreted by intestinal L-cells in response to food intake. It signals the pancreas to secrete insulin in a glucose-dependent manner, suppresses glucagon secretion, slows gastric emptying, and acts on the hypothalamus to reduce appetite. GLP-1 receptor agonists are drugs designed to bind and activate the GLP-1 receptor with longer duration of action than native GLP-1, which has a half-life of only minutes in the bloodstream.
The class has grown substantially. Earlier GLP-1 medications (liraglutide, exenatide) required daily injection. Semaglutide introduced once-weekly subcutaneous dosing, and later an oral formulation. Tirzepatide added simultaneous GIP receptor activation, a dual mechanism with clinical implications for efficacy.
What is semaglutide, and why is it the established standard?
Semaglutide is a GLP-1 receptor agonist with a half-life of approximately one week, allowing once-weekly subcutaneous dosing. It is also available as a daily oral tablet (though with significantly lower bioavailability requiring a specialized formulation with SNAC absorption enhancer).
The STEP 1 trial of subcutaneous semaglutide at 2.4 mg weekly in adults with overweight or obesity (without type 2 diabetes) showed a mean weight reduction of 14.9% of body weight over 68 weeks, compared to 2.4% for placebo. The drug is compounded in the USA by licensed 503A pharmacies, allowing broader access at lower cost than brand-name alternatives during the period of FDA-declared shortage.
Semaglutide is PepScribe’s most established GLP-1 offering. Learn more about compounded semaglutide protocols.
Why does tirzepatide have stronger trial data?
Tirzepatide activates both the GIP receptor and the GLP-1 receptor. GIP (glucose-dependent insulinotropic polypeptide) is another incretin hormone with distinct but complementary actions: it amplifies insulin secretion, may promote fat storage at lower glucose states, and in combination with GLP-1 receptor activation appears to compound satiety signaling.
In the SURMOUNT-1 trial, tirzepatide at 15 mg weekly produced a mean weight reduction of 20.9% over 72 weeks — the largest average weight reduction recorded for a once-weekly injectable in a major phase 3 trial at that time. The SURMOUNT-5 head-to-head trial directly compared tirzepatide to semaglutide and found tirzepatide produced greater weight reduction on average at maximum approved doses.
Tirzepatide is available through licensed 503A compounding pharmacies in the USA. Learn more about compounded tirzepatide protocols.
How do semaglutide and tirzepatide compare? Trial data summary
| Parameter | Semaglutide 2.4 mg | Tirzepatide 15 mg |
|---|---|---|
| Mechanism | GLP-1 agonist | GIP + GLP-1 dual agonist |
| Dosing | Once weekly SC | Once weekly SC |
| Mean weight reduction (trial peak dose) | ~14.9% (STEP 1) | ~20.9% (SURMOUNT-1) |
| Common GI side effects | Nausea, diarrhea, vomiting | Nausea, diarrhea, vomiting |
| Compounded available | Yes (503A) | Yes (503A) |
Note: mean weight reductions from separate trials with different populations and protocols. Direct comparisons across trials should be interpreted cautiously. SURMOUNT-5 (head-to-head) found tirzepatide superior to semaglutide at maximum doses in the same trial design.
What other GLP-1 class medications exist?
The GLP-1 class includes older agents that predate semaglutide and tirzepatide:
- Liraglutide (Saxenda for obesity): Requires daily injection. Showed approximately 5–8% mean weight reduction in major trials, less than the once-weekly agents. Largely superseded by semaglutide for weight management but remains FDA-approved for obesity.
- Exenatide (Byetta, Bydureon): Indicated for type 2 diabetes. Available twice daily (Byetta) or once weekly extended release (Bydureon). Not primarily indicated for weight management, and trial weight-loss data is substantially lower than semaglutide or tirzepatide.
- Dulaglutide (Trulicity): Once-weekly GLP-1 agonist indicated for type 2 diabetes with a secondary cardiovascular outcomes indication. Weight reduction data is modest compared to semaglutide and tirzepatide.
For patients specifically seeking weight management support, semaglutide and tirzepatide have the strongest efficacy data and are the primary focus of clinician-supervised protocols at PepScribe.
How do brand-name and compounded GLP-1 medications differ in access and cost?
Brand-name GLP-1 medications carry substantial list prices and face formulary restrictions that make access inconsistent without commercial insurance with specific coverage, or Medicaid. Compounded semaglutide and tirzepatide are available through licensed 503A pharmacies in the USA under a clinician prescription, typically at substantially lower out-of-pocket cost.
Compounded GLP-1 medications are not FDA-approved products and are not FDA-approved generics. They are custom preparations of the same active pharmaceutical ingredient, prepared by licensed 503A pharmacies under applicable federal and state regulatory requirements. This is not a gray-market or overseas arrangement: 503A compounding pharmacies in the USA operate under FDA and state board of pharmacy oversight.
PepScribe uses licensed USA 503A pharmacies exclusively. No hidden overseas supply chain. Clinician oversight is built into every protocol — not optional.
Common questions about GLP-1 medications
What are the main GLP-1 medications available?
The most clinically studied GLP-1 receptor agonists for weight management are semaglutide (once weekly injection or daily oral) and tirzepatide (once weekly injection, a dual GIP/GLP-1 agonist). These are prescription medications available as brand-name products or, through licensed 503A compounding pharmacies under a clinician prescription, as compounded formulations.
Is tirzepatide better than semaglutide for weight loss?
In the SURMOUNT-5 head-to-head trial, tirzepatide at its maximum dose produced greater average weight reduction than semaglutide at its maximum dose. Individual response varies; a clinician evaluates your history and goals to recommend a starting point. One medication being stronger on average does not mean it is right for every patient.
What is the difference between GLP-1 and GIP/GLP-1 dual agonists?
GLP-1 receptor agonists (like semaglutide) activate only the GLP-1 receptor. Dual GIP/GLP-1 agonists (like tirzepatide) also activate the GIP receptor. GIP activity may amplify insulin release and affect fat cell metabolism in ways that compound the effects of GLP-1 alone, which is proposed to explain tirzepatide's stronger average weight-loss signal in trials.
Can I switch between GLP-1 medications?
Switching is possible and sometimes clinically appropriate — for example, if one medication is not tolerated or if insurance or access changes. Switches require clinical guidance on dose conversion and titration. Do not switch without talking to your prescribing clinician.
Are compounded GLP-1 medications the same as brand-name versions?
Compounded semaglutide and tirzepatide use the same active pharmaceutical ingredient as brand-name versions but are not FDA-approved products — they are custom preparations by licensed 503A compounding pharmacies. They are not bioequivalent FDA-approved generics. A licensed clinician prescribes the formulation to specification.