Current research on GLP-1–related compounds (semaglutide, tirzepatide, retatrutide, and AOD-9604)

In the past few years, few areas of medicine have generated as much attention — and as much confusion — as GLP-1–related compounds. Headlines promise dramatic results. Social media is filled with personal stories. At the same time, regulatory warnings, compounding debates, and ongoing clinical trials create a complex picture that is difficult for most people to navigate.

This educational guide cuts through the noise. It explains what semaglutide, tirzepatide, retatrutide, and AOD-9604 actually are, how they work according to current science, what the major clinical trials have shown as of mid-2026, how these compounds are being discussed in the market, and the key questions worth asking a licensed healthcare provider. The goal is simple: give you clear, evidence-based context so you can have more informed conversations.

Important disclaimer: This article is strictly educational. It is not medical advice and does not recommend, promote, or endorse any medication, compounded product, or treatment. Compounded drugs are not FDA-approved and have not been reviewed by the FDA for safety, effectiveness, or quality. Retatrutide is an investigational drug and is not approved for any use. Always consult a licensed healthcare provider for decisions about your health. Research findings describe average results in specific trial populations and do not predict individual outcomes.

What are semaglutide, tirzepatide, retatrutide, and AOD-9604?

These are peptide-based compounds that interact with receptors involved in appetite, insulin regulation, and energy balance:

• Semaglutide — A selective GLP-1 receptor agonist. FDA-approved in branded forms for type 2 diabetes and chronic weight management.
• Tirzepatide — A dual agonist that activates both GIP and GLP-1 receptors. FDA-approved in branded forms for type 2 diabetes and chronic weight management.
• Retatrutide — An investigational triple agonist targeting GIP, GLP-1, and glucagon receptors. Currently in Phase 3 trials; not FDA-approved.
• AOD-9604 — A synthetic fragment of human growth hormone. Not FDA-approved for any indication; earlier development focused on potential metabolic effects.

Understanding the difference between FDA-approved products and investigational or compounded versions is essential for evaluating any information you encounter online.

How do these compounds work?

At a high level, these molecules influence several biological pathways:

• GLP-1 receptor activation helps regulate appetite, slows gastric emptying, and supports glucose-dependent insulin release.
• GIP receptor activation (present in tirzepatide and retatrutide) may provide additional effects on insulin response and energy metabolism.
• Glucagon receptor activation (unique to retatrutide among this group) is being studied for potential effects on energy expenditure.
• AOD-9604 was designed to capture certain metabolic signaling aspects of growth hormone without the full range of growth-hormone activity. Human data on its precise mechanism remain limited.

These are simplified descriptions. The actual physiology is complex, and effects observed in controlled trials do not automatically apply to every person or to non-approved formulations.

What does the latest GLP-1 research show? (Key clinical findings as of August 2026)

Semaglutide

The STEP clinical trial program established significant average weight reduction in people with obesity (typically in the mid-teens percentage range at higher doses). The SELECT cardiovascular outcomes trial demonstrated a reduction in major adverse cardiovascular events in people with overweight or obesity and established cardiovascular disease.

Transparent view of the cited studies:

• STEP clinical trial program (weight reduction in mid-teens % range at higher doses): Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384(11):989-1002. doi:10.1056/NEJMoa2032183 (STEP 1: mean weight loss of 14.9% with 2.4 mg semaglutide at 68 weeks.)
• SELECT cardiovascular outcomes trial: Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes. N Engl J Med. 2023;389(24):2221-2232. doi:10.1056/NEJMoa2307563 (Demonstrated a 20% relative risk reduction in major adverse cardiovascular events.)

Tirzepatide

The SURMOUNT Phase 3 program reported average weight reductions of approximately 15–21% at higher doses over 72 weeks. In the head-to-head SURMOUNT-5 trial, tirzepatide produced greater average weight loss than semaglutide (approximately 20.2% versus 13.7% at week 72) in adults with obesity without diabetes.

Transparent view of the cited studies:

• SURMOUNT Phase 3 program (approximately 15–21% weight reduction) Supported by the broader SURMOUNT series (SURMOUNT-1 and related trials published in N Engl J Med 2022–2023). View article here.
• SURMOUNT-5 head-to-head trial (20.2% vs 13.7% at week 72) Aronne LJ, Horn DB, le Roux CW, et al. Tirzepatide as Compared with Semaglutide for the Treatment of Obesity. N Engl J Med. 2025;393(1):26-36. doi:10.1056/NEJMoa2416394 (Least-squares mean percent change in weight: −20.2% with tirzepatide vs −13.7% with semaglutide; P<0.001.)

Retatrutide

Multiple Phase 3 TRIUMPH trials have reported topline results in 2026. Depending on the population (obesity without diabetes, obesity with type 2 diabetes, or obesity with cardiovascular disease), average weight reductions at higher doses over roughly 80 weeks have ranged from the low-20% to upper-20% range in published topline data. Glycemic improvements have also been observed. As of July 2026, regulatory submission is projected for early 2027.

Retatrutide remains investigational and is not approved. The FDA has stated it cannot be used in compounding under current federal rules.

Transparent view of the cited studies:

• TRIUMPH Phase 3 topline results (low-20% to upper-20% range at higher doses over ~80 weeks) Eli Lilly and Company. Lilly’s triple agonist, retatrutide, successful in two additional Phase 3 obesity trials, delivering significant improvements in weight and A1C. Press release, July 23, 2026.
• TRIUMPH-2 (obesity/overweight + type 2 diabetes): up to 20.8% mean weight loss at 12 mg. View article here.
• TRIUMPH-3 (severe obesity + established cardiovascular disease): up to 22.6% mean weight loss at 12 mg. (Detailed results to be presented at future medical meetings and published in peer-reviewed journals. ClinicalTrials.gov: NCT05929079 and NCT05882045.) View U.S. government trial updates here.

AOD-9604

Human evidence is older and more limited. Early smaller studies suggested possible modest effects. The larger Phase 2b OPTIONS trial (approximately 500 participants over 24 weeks) did not meet its primary weight-loss endpoint compared with placebo when diet and exercise were included. Development for obesity was discontinued. Available safety data from the trial program were generally comparable to placebo, but efficacy signals were inconsistent.

Transparent view of the cited studies:

• Larger Phase 2b OPTIONS trial (~500 participants, 24 weeks; primary endpoint not met) Metabolic Pharmaceuticals Limited. Phase 2B clinical trial results announcement for AOD9604 (OPTIONS Study). Public company announcement / Australian Stock Exchange filing, 2007. (Summarized in subsequent literature and FDA Pharmacy Compounding Advisory Committee briefing documents: no statistically significant weight loss vs placebo when diet and exercise were included; development for obesity terminated.) View source here.
• Safety data across the trial program Stier H, Vos E, Kenley D. Safety and Tolerability of the Hexadecapeptide AOD9604 in Humans. Journal of Endocrinology and Metabolism. 2013;3(1-2):7-15. doi:10.4021/jem157w (Pooled analysis of six randomized, double-blind, placebo-controlled trials; safety profile generally comparable to placebo.)

How these GLP-1 compounds are currently discussed and marketed

FDA-approved branded versions of semaglutide and tirzepatide are promoted through established pharmaceutical channels under approved labeling.

In parallel, compounded versions of certain peptides and investigational agents have been marketed online and through some clinics. Regulatory agencies have issued multiple warning letters addressing claims that imply compounded products are equivalent to approved drugs, “clinically proven,” or identical in quality. The FDA has emphasized that compounded drugs are not reviewed for safety, effectiveness, or quality before marketing, and that retatrutide cannot legally be compounded.

Clear educational content that distinguishes approved products, investigational compounds, and compounded versions helps reduce confusion for people researching these topics.

Who may be eligible for GLP-1s in a clinical setting?

Eligibility for FDA-approved products is determined by licensed clinicians according to labeled indications, contraindications, medical history, and individual factors (such as BMI thresholds, presence of type 2 diabetes or weight-related conditions, and personal or family history of certain thyroid conditions).

Investigational agents such as retatrutide are available only through formal clinical trials. AOD-9604 has no approved indication. Any assessment of potential suitability is the responsibility of a licensed healthcare provider after appropriate evaluation.

Interested in learning more about GLP-1s for your weight management goals? Visit our SFS Wellness protocol page to learn more about your options. Learn more here.

What to look for when choosing a provider or evaluating information on GLP-1s

When reviewing options or speaking with a provider, useful points to consider include:

• Whether the provider conducts a genuine medical evaluation (history, relevant labs when indicated, discussion of risks and alternatives)
• Clear distinction between FDA-approved products and compounded or investigational options
• Transparent acknowledgment that compounded drugs are not FDA-approved
• Avoidance of outcome guarantees or claims that a compounded product is “the same as” an approved drug
• Discussion of monitoring, common side effects (frequently gastrointestinal with the incretin class), and longer-term considerations
• Use of legitimate pharmacy channels for any prescribed medication
• Reliable educational sources cite primary trial publications and official regulatory statements rather than promotional claims.

SFS Wellness was built specifically around these principles. We function as an educational resource partner—not a medical practice—so our focus stays on clear, evidence-based information rather than sales pressure. We help you understand the difference between FDA-approved products, compounded options, and investigational compounds. We explain the typical process (including when a licensed provider consultation is required), outline what to expect with monitoring and common side effects, and connect you only to pathways that use licensed providers and legitimate compounding pharmacy channels when a prescription is involved.

Want to learn more without the pressure of purchasing? Our non-medical consultations are free (opens an external Calendly scheduling page) and carry no obligation. They exist to give you clearer context and the right questions to ask, so any conversation you later have with a licensed clinician is more informed. Education comes first; medical decisions remain entirely with independent licensed providers.

Frequently asked questions about GLP-1s

Ready to learn more about GLP-1s?

If this overview has helped clarify the current research landscape, SFS Wellness offers additional educational resources on weight management approaches and a clear explanation of the typical next steps. You can explore available options, understand the process (including when a licensed provider consultation is involved), and get straightforward information—with no pressure and no obligation.