Update — ADA 2026: the new GLP-1 data at a glance
At the 2026 ADA congress the first major results for the next generation of GLP-1 agents were presented. Retatrutide, a triple agonist, showed roughly 20 percent weight loss in TRIUMPH-1 after 80 weeks. At the highest dose this rose to more than 30 percent after 104 weeks. In TRANSCEND-T2D-1, HbA1c fell by about 2 percentage points. Anyone following retatrutide research in 2026 has the key figures here.
Survodutide is a dual agonist at the GLP-1 and glucagon receptor. In SYNCHRONIZE-1, weight loss at the highest dose came to 16.6 percent. In the liver study SYNCHRONIZE-MASLD, 84 percent of participants achieved a reduction in liver fat of more than 30 percent, against 24 percent in the placebo group. Weight loss in that study was 12 percent.
The oral agents also came into view. In SOLSTICE, elecoglipron lowered HbA1c by 1.9 percentage points; oral semaglutide reached 1.3 percentage points in the same comparison. In VISTA, weight loss was 10.5 percent after 36 weeks, but roughly a third of participants on the highest dose discontinued early. In ACCESS, aleniglipron reached 11.3 percent after 38 weeks and 16 percent in the open-label extension after 56 weeks.
For CagriSema the REIMAGINE programme was presented: three phase 3 studies in which the combination worked better than cagrilintide or semaglutide alone, with limited additional gastrointestinal complaints.
One nuance belongs with this. These are controlled clinical studies in patients, conducted and funded by pharmaceutical companies. The discontinuation figures show that more effect also means more side effects. These results say nothing about use outside that study context. All peptides at Peplife are Research Use Only and intended solely for laboratory research.
Sources: Docwire News — ADA 2026 obesity drug updates · Nature Medicine — SYNCHRONIZE-MASLD phase 3 · Managed Healthcare Executive — retatrutide at ADA 2026, SYNCHRONIZE-1 appeared in the New England Journal of Medicine.
In brief · RUO
- GLP-1 is a gut hormone that, after eating, triggers insulin, curbs appetite and slows stomach emptying. Researchers mimic it with receptor agonists — peptides that "press" the same receptor.
- The field is shifting from one target (semaglutide) to two (tirzepatide: GIP+GLP-1) and three (retatrutide: +glucagon), plus amylin combinations (CagriSema).
- In 2025 the first head-to-head appeared (SURMOUNT-5): tirzepatide > semaglutide. Retatrutide reached ~28–30% weight loss in phase 3 (TRIUMPH-1, 2026).
- Applications are growing: beyond weight, also the liver (MASH), and there's a first oral pill (Dec 2025).
- Key nuance: stronger effects come with side effects (gastrointestinal, muscle-mass loss, a rare eye effect) that research explicitly weighs.
- This article discusses research. Peplife supplies these compounds strictly Research Use Only — no medical or usage advice.
What is this about?
After a meal, your gut releases hormones telling the body "food is coming." The best known is GLP-1 (glucagon-like peptide-1). It does three things at once: it prompts the pancreas to release insulin (but only when blood sugar is high, keeping the risk of low sugar small), it curbs appetite via the brain, and it slows how fast the stomach empties — so you feel full longer. Natural GLP-1 is, however, broken down within minutes. The breakthrough of recent years was building GLP-1 receptor agonists: peptides that activate the same receptor but last far longer, so one weekly injection suffices.
What does "agonist" mean? An agonist activates a receptor (a lock on the cell), like the natural key. A dualagonist fits two locks; a tripleagonist, three. More locks at once can give a stronger or broader effect — but also more places where side effects can arise.
Under the hood: which hormone does what?
To see why "the next generation" is different, it helps to know what each hormone contributes:
- GLP-1 — curbs appetite, stimulates insulin, slows stomach emptying. The foundation.
- GIP (glucose-dependent insulinotropic polypeptide) — a second gut hormone that also boosts the insulin response and, combined with GLP-1, appears to increase the effect on weight and blood sugar and may ease some side effects (nausea).
- Glucagon — normally insulin's "counter-hormone," but in a low, balanced dose it raises energy expenditure and acts on the liver. Hence its addition to triple agonists.
- Amylin — a separate satiety hormone from the pancreas; an amylin analog (cagrilintide) complements GLP-1 via a different route.
What does this mean? "More receptors" is not a trick to simply crank up the dose; it combines different natural signals that each touch a distinct side of metabolism. That is the core of why triple agonists go further in trials than mono agonists.
From mono to dual to triple agonist
Semaglutide is the mono agonist (GLP-1 only). Tirzepatide adds GIP (dual). Retatrutide adds glucagon (triple, "triple G" in the literature).
The first large head-to-head, SURMOUNT-5 (2025), placed tirzepatide and semaglutide side by side for 72 weeks in people with obesity. Tirzepatide produced significantly more weight loss and waist reduction (NEJM 2025). Retatrutide went further in phase 3 (TRIUMPH-1, May 2026): up to ~28.3% mean weight loss at 80 weeks, ~30% in a subgroup at 104 weeks (manufacturer release, NCT05929066). The phase 2 basis is in NEJM 2023.
Overview: the key agents
| Agent | Target(s) | Key trial | Reported result | Administration |
|---|---|---|---|---|
| Semaglutide | GLP-1 | SURMOUNT-5 (comparator) | reference; oral form approved 2025 | injection / oral |
| Tirzepatide | GIP + GLP-1 | SURMOUNT-5 | more weight loss than semaglutide | injection |
| Retatrutide | GIP + GLP-1 + glucagon | TRIUMPH-1 (phase 3) | ~28–30% weight loss | injection |
| CagriSema | GLP-1 + amylin | REDEFINE 1 | ~22.7% weight loss | injection |
| Survodutide | glucagon + GLP-1 | phase 2 MASH | improved liver inflammation + fibrosis | injection |
Study type: randomized clinical trials (RCTs) in humans; TRIUMPH-1 figures from a manufacturer release (to be confirmed in publication).
Adding amylin: CagriSema
Another direction combines semaglutide with cagrilintide, an amylin analog. Because amylin gives satiety via its own route, the idea is that the two complement each other. In REDEFINE 1 (2025) the combination gave ~22.7% weight loss in people with obesity (NEJM); REDEFINE 2 confirmed added benefit in type 2 diabetes (PubMed).
Beyond weight: the liver and more
The class is studied more broadly than weight loss alone. Survodutide (glucagon/GLP-1) improved fatty-liver-with-inflammation (MASH) and fibrosis in a phase 2 study (NEJM 2024) — logically, since the glucagon component acts directly on the liver. An authoritative 2025 review lays out the emerging areas (liver, heart, brain) (Nature Reviews Drug Discovery 2025). (We expand the liver application in the pillar [Peptides and fatty liver (MASH)].)
The pill is coming
Because the stomach breaks peptides down, GLP-1s were injections until recently. In December 2025 the FDA approved the first oral GLP-1 pill for weight management (oral semaglutide, ~13.6% in OASIS 4), made possible by special excipients that protect the peptide (AJMC). There is also orforglipron — an oral small molecule (not a peptide) acting on the same receptor, heading toward global filing in 2025 (The Lancet02165-8/abstract)). A pill is usually somewhat less powerful than the strongest injection but lowers the barrier considerably.
Bioglutide (NA-931): a pill that is not a peptide
Alongside oral semaglutide, a second route towards the pill is under way: small molecules that activate the receptors without being a peptide themselves. Bioglutide, with development code NA-931 from Biomed Industries, is the most frequently cited example. It is presented as an orally active quadruple receptor agonist that acts simultaneously on the IGF-1, GLP-1, GIP and glucagon receptor.
In a thirteen-week phase 2 study the manufacturer reported an average weight change of minus 13.8 percent from baseline at 150 mg per day, or minus 11.9 percent placebo-adjusted. Roughly 72 percent of participants reached at least 12 percent weight loss after thirteen weeks, against 1.9 percent in the placebo group. The gastrointestinal complaints reported were predominantly mild.
At the ADA meeting of June 2026 Biomed presented the phase 3 programme. BIOCOMBO-1 is a 68-week study in roughly 466 adults with overweight or obesity without diabetes, with two arms: NA-931 120 mg per day as monotherapy and NA-931 120 mg combined with oral semaglutide 12.5 mg per day.
This compound comes with an explicit caveat. Bioglutide is not a peptide but a small molecule of roughly 500 daltons, derived from cyclic glycyl-proline. The molecular formula has not been disclosed, there is no CAS number and there is no published structure. Virtually all available figures come from manufacturer press releases and not from peer-reviewed publications. In trade the label GLP-4 agonist turns up; that is a marketing term and not an existing receptor class.
For laboratory research that creates a concrete problem. Without a public formula or CAS number, a certificate of analysis cannot be checked against a reference standard. Peplife therefore does not carry bioglutide in its standard range. Supply is exclusively on request and after consultation about identity verification.
Sources for this section: Biomed Industries — phase 3 programme NA-931, ADA 2026 · Biomed Industries — company information
Interested in bioglutide or eloralintide?
These compounds are not part of our standard range. Supply can still be discussed on request, subject to availability and to identity verification on the batch. Tell us briefly what your research requires and we will come back to you on what is possible.
The other side: side effects and nuance
Stronger effects don't come free. Research pays explicit attention to the downsides:
- Gastrointestinal complaints (nausea, vomiting, diarrhea) are the most common side effect, especially when escalating the dose — partly a result of slowed stomach emptying.
- Loss of muscle mass: large weight loss is not only fat; some is muscle. This is an active research area (e.g., combinations with muscle-preserving agents).
- Rare eye side effect: the EMA added NAION as a very rare side effect of semaglutide in 2025 (fewer than 1 in 10,000) — see the bulletin.
- Weight often returns after stopping, raising questions about long-term use.
What does this mean? "Works strongly in a trial" and "suitable for everyone" are not the same. Science weighs effect against side effects; we discuss both and give no usage advice.
Regulation is keeping pace
- FDA: the semaglutide and tirzepatide shortages were resolved in 2025, ending the window for large-scale compounding (FDA).
- EMA: NAION added as a very rare side effect (Pharmaceutical Journal).
- WHO/FDA: repeated warnings about counterfeit semaglutide (FDA) — underscoring why provenance and independent testing matter.
Related research · RUO
- Knowledge base: Semaglutide vs Tirzepatide, comparing GLP-1 peptides and Peptides and fatty liver (MASH) (internal pillars that go deeper on the direct comparison and the liver application).
- RUO research materials in the catalog: semaglutide, tirzepatide, retatrutide, survodutide, cagrilintide (laboratory research only).
Further reading: Amylin vs incretin compared · comparing GLP-1 peptides · Retatrutide vs tirzepatide vs semaglutide · Eloralintide and the amylin agonists · CagriSema research · Peptides and fatty liver (MASH)
Frequently asked questions
What is the difference between a mono, dual and triple agonist?
The number of hormone receptors the peptide activates at once: one (semaglutide: GLP-1), two (tirzepatide: GIP+GLP-1), or three (retatrutide: +glucagon). Each hormone touches a different side of metabolism.
Why add glucagon — doesn't it raise blood sugar?
In a low, balanced dose within a triple agonist, its effect on energy expenditure and the liver dominates; the GLP-1 and GIP components keep blood sugar in check.
Is tirzepatide "better" than semaglutide?
In SURMOUNT-5 tirzepatide gave more weight loss. "Better" depends on context and side effects; this is research data, not advice.
What is CagriSema?
A research combination of semaglutide with the amylin analog cagrilintide — two satiety routes at once.
Does Peplife supply a CoA with these compounds?
Yes — all RUO materials are independently tested with a CoA per batch.
What is bioglutide (NA-931)?
Bioglutide is the brand name Biomed Industries uses for NA-931, an oral small molecule that according to the manufacturer acts on the IGF-1, GLP-1, GIP and glucagon receptor. It is emphatically not a peptide and the structure is not public. The reported phase 2 outcome was minus 13.8 percent weight change after thirteen weeks at 150 mg per day. Peplife supplies it exclusively on request and not from the standard range.
Disclaimer
This article discusses scientific research and regulation and is informational only. The compounds mentioned are supplied by Peplife strictly as Research Use Only (RUO) for laboratory research. Nothing here is medical, diagnostic, or dosing advice. Named medicines are cited only to discuss published research.