Elecoglipron
Medium EvidenceAn investigational, once-daily oral small-molecule GLP-1 receptor agonist from AstraZeneca that delivered up to about 11.8% weight loss at 36 weeks in people with obesity or overweight and strong blood-sugar control in type 2 diabetes, and is now advancing into a large Phase 3 program. Unlike semaglutide and tirzepatide - which are injectable peptides - elecoglipron is a small chemical molecule that mimics the natural GLP-1 hormone at its receptor in the gut and hypothalamus, so it can be taken as a pill with no food or fasting restrictions and is easier and cheaper to manufacture at global scale than peptide drugs. In the Phase 2b VISTA trial (n=310) the 75 mg once-daily regimen produced an average body-weight reduction of 10.5% at 26 weeks (vs 0.6% placebo) that had not plateaued, reaching about 11.8% at 36 weeks, with up to 88.8% of participants achieving at least 5% weight loss. In the Phase 2b SOLSTICE trial in type 2 diabetes (n=404) the 75 mg regimen cut HbA1c by 1.9% at 26 weeks (vs 0.2% placebo) - with roughly 90% of participants reaching an HbA1c below 7% - alongside 7.7% weight loss, numerically ahead of an open-label oral semaglutide 14 mg comparator arm. Side effects were the familiar GLP-1 class gastrointestinal symptoms (nausea, constipation, diarrhea, vomiting), mostly mild to moderate, with infrequent discontinuations and no liver safety signals. Both trials were presented at the 2026 American Diabetes Association (ADA) Scientific Sessions in New Orleans and published simultaneously in The Lancet, and on June 8, 2026 AstraZeneca announced elecoglipron would move into an extensive Phase 3 program - the EMBOLD obesity trials and the ELUMINATE type 2 diabetes trials (including combination with dapagliflozin), plus cardiovascular and kidney outcome studies. Elecoglipron is an investigational prescription-stage medicine - it is not approved anywhere and is not a supplement or research chemical.
What It Is
Elecoglipron (development codes AZD5004 / ECC5004) is AstraZeneca's investigational once-daily oral small-molecule GLP-1 receptor agonist (GLP-1 RA), a cornerstone of the company's cardiovascular-renal-metabolism (CVRM) weight-management strategy. GLP-1 receptor agonists lower blood sugar and body weight by mimicking glucagon-like peptide-1: they enhance glucose-dependent insulin secretion, suppress glucagon, slow gastric emptying and act on appetite centers in the brain. The market-leading GLP-1 medicines - semaglutide (Ozempic/Wegovy) and the GLP-1/GIP dual agonist tirzepatide - are peptides that must be injected or, in oral peptide form, taken under fasting conditions with tight absorption limits. Elecoglipron instead is a non-peptide chemical molecule that binds and activates the GLP-1 receptor directly, which allows convenient once-daily oral tablet dosing with no food or fasting restrictions and offers manufacturing scalability and cost advantages over peptides - the same 'oral small-molecule GLP-1' thesis pursued by orforglipron (Eli Lilly), aleniglipron, danuglipron (Pfizer) and others. Elecoglipron originated from Eccogene (as ECC5004) and was licensed by AstraZeneca in 2023. In the global, randomized, double-blind Phase 2b VISTA trial (n=310, seven countries; adults with obesity or overweight and at least one weight-related comorbidity, mean baseline weight 106.9 kg), the co-primary endpoints were percent body-weight change and the proportion achieving at least 5% weight loss at 26 weeks. The 75 mg once-daily regimen produced an average weight reduction of 10.5% at 26 weeks versus 0.6% with placebo; weight loss did not plateau and reached about 11.8% at 36 weeks (vs 0.3% placebo), with up to 88.8% of participants achieving at least 5% weight loss at 26 weeks and roughly 62% achieving at least 10% and about 40% achieving at least 15% at 36 weeks. Exploratory analyses showed reductions in blood pressure and C-reactive protein, a marker of systemic inflammation. In the parallel Phase 2b SOLSTICE trial (n=404, nine countries; adults with type 2 diabetes, mean baseline HbA1c 7.9%), the primary endpoint was HbA1c change at 26 weeks: elecoglipron 75 mg lowered HbA1c by 1.9% versus 0.2% with placebo, with 90% of participants reaching an HbA1c below 7% and 85% reaching 6.5% or lower, alongside 7.7% weight loss - numerically greater than the study's open-label oral semaglutide 14 mg comparator arm (HbA1c -1.3%, weight -5.1%). Across both trials the safety profile was consistent with the GLP-1 class: adverse events were predominantly gastrointestinal and mild to moderate (in VISTA, nausea 55%, constipation 41%, diarrhea 35%, vomiting 29% with 75 mg vs placebo), discontinuations for adverse events were infrequent, no liver safety signals emerged, and hypoglycemia was uncommon in the diabetes population. The Phase 2 tolerability data were used to refine the dose-escalation schedule for Phase 3. Both trials were reported at the 2026 ADA Scientific Sessions and published in The Lancet, and on June 8, 2026 AstraZeneca announced the extensive Phase 3 program: the EMBOLD trials in obesity or overweight (with and without type 2 diabetes), the ELUMINATE trials in type 2 diabetes (elecoglipron as monotherapy and in combination with the SGLT2 inhibitor dapagliflozin), and additional long-term cardiovascular and kidney outcome trials. Elecoglipron has no regulatory approval anywhere; it is an investigational medicine studied only within AstraZeneca's clinical trials, and head-to-head superiority over semaglutide or tirzepatide has not been established.
Regulatory Status
Not approved by the FDA, EMA or any regulator. Elecoglipron is an investigational oral small-molecule GLP-1 receptor agonist in clinical development. Following positive Phase 2b VISTA (obesity/overweight) and SOLSTICE (type 2 diabetes) results reported at ADA 2026 and published in The Lancet, AstraZeneca announced on June 8, 2026 that it is advancing elecoglipron into an extensive Phase 3 program (EMBOLD in obesity; ELUMINATE in type 2 diabetes, including combination with dapagliflozin) plus cardiovascular and kidney outcome trials. Available only within clinical trials.
Effective: June 2026
View FDA SourceWhy Researchers Study It
Elecoglipron is one of the leading tests of whether a convenient, scalable ORAL small-molecule GLP-1 pill can match the weight-loss and blood-sugar benefits that made injectable peptides like semaglutide and tirzepatide blockbusters. Injectable and oral-peptide GLP-1 drugs are effective but constrained by needle-based delivery or strict fasting requirements, complex peptide manufacturing and supply bottlenecks, and high cost - limits that keep them out of reach for many of the nearly three billion people worldwide living with obesity or overweight. A non-peptide small molecule that can be mass-produced as a simple daily tablet with no food restrictions could dramatically widen access. Researchers watch elecoglipron because its Phase 2b data put it among the more potent oral GLP-1 candidates (about 11.8% weight loss at 36 weeks and a 1.9% HbA1c drop), because its non-plateauing weight curve suggests further loss with longer treatment, and because AstraZeneca is testing it not just as a monotherapy but in combinations (for example with the SGLT2 inhibitor dapagliflozin) and in dedicated cardiovascular and kidney outcome trials - the studies that determine whether metabolic improvement translates into fewer heart and kidney events. Its trajectory will help define how the crowded oral small-molecule GLP-1 field (orforglipron, aleniglipron, danuglipron and others) shakes out on efficacy, tolerability and real-world scalability.
Proposed Mechanisms
- GLP-1 receptor agonism: elecoglipron is a non-peptide small molecule that binds and activates the glucagon-like peptide-1 (GLP-1) receptor, mimicking the natural incretin hormone at receptors in the gut and hypothalamus as part of the brain-gut axis that regulates food intake and metabolism.
- Appetite suppression and reduced food intake: by activating GLP-1 receptors in hypothalamic appetite centers, it lowers hunger and caloric intake, driving progressive body-weight loss that had not plateaued by 36 weeks in the VISTA trial.
- Glucose-dependent insulin secretion and glucagon suppression: like the GLP-1 class it enhances insulin release in a glucose-dependent manner and suppresses glucagon, lowering HbA1c (by 1.9% at 26 weeks in SOLSTICE) while keeping hypoglycemia uncommon.
- Slowed gastric emptying: GLP-1 receptor activation delays gastric emptying, promoting satiety - and, as a class effect, contributing to the predominantly gastrointestinal side effects (nausea, constipation, diarrhea, vomiting).
- Oral small-molecule delivery advantage: as a chemical (non-peptide) agonist, elecoglipron can be taken as a once-daily tablet with no food or fasting restrictions and manufactured at large scale more easily and cheaply than injectable or oral-peptide GLP-1 drugs, the central rationale for the oral small-molecule GLP-1 class.
- Broader cardiometabolic effects: exploratory VISTA analyses showed reductions in blood pressure and C-reactive protein (a systemic-inflammation marker), consistent with weight loss and GLP-1 signaling and motivating dedicated cardiovascular and kidney outcome trials.
Evidence Snapshot
| Study Type | Model | Outcome | Link |
|---|---|---|---|
| Phase 2b randomized, double-blind, placebo-controlled trial in obesity/overweight (VISTA) | 310 adults with obesity or overweight and at least one weight-related comorbidity (mean baseline weight 106.9 kg) across seven countries; once-daily oral elecoglipron at fixed doses (5 mg, 15 mg) and escalated regimens (50 mg, 75 mg) vs placebo, with diet and activity advice; 36-week total duration. | Co-primary endpoints met: average body-weight change of -10.5% at 26 weeks with 75 mg vs -0.6% placebo, reaching about -11.8% at 36 weeks (no plateau); up to 88.8% of participants achieved >=5% weight loss at 26 weeks, ~62% achieved >=10% and ~40% achieved >=15% at 36 weeks. Exploratory reductions in blood pressure and C-reactive protein. | Source |
| Phase 2b randomized, double-blind, placebo-controlled trial in type 2 diabetes (SOLSTICE) | 404 adults with type 2 diabetes (mean baseline HbA1c 7.9%) across nine countries; once-daily oral elecoglipron at fixed doses (5, 15, 25 mg) and escalated regimens (50, 75 mg) vs placebo, with an open-label oral semaglutide 14 mg exploratory comparator arm; 26-week primary timepoint. | Primary endpoint met: HbA1c change of -1.9% at 26 weeks with 75 mg vs -0.2% placebo; ~90% reached HbA1c <7% and ~85% reached <=6.5%; average weight change -7.7% - numerically greater than the open-label oral semaglutide 14 mg arm (HbA1c -1.3%, weight -5.1%). Hypoglycemia uncommon. | Source |
| Pooled Phase 2b safety and tolerability | Adverse-event and laboratory data from VISTA and SOLSTICE at the 75 mg regimen vs placebo. | Safety consistent with the GLP-1 class: predominantly mild-to-moderate gastrointestinal events (VISTA 75 mg vs placebo: nausea 55% vs 20%, constipation 41% vs 6%, diarrhea 35% vs 25%, vomiting 29% vs 5%); discontinuations for adverse events infrequent; no liver safety signals; no serious hypoglycemia-related events. Data informed the Phase 3 dose-escalation schedule. | Source |
| Phase 3 program (announced, initiating) | EMBOLD Phase 3 trials in obesity or overweight (with and without type 2 diabetes); ELUMINATE Phase 3 trials in type 2 diabetes (elecoglipron monotherapy and in combination with dapagliflozin); plus long-term cardiovascular and kidney outcome trials. | Planned/initiating - designed to confirm the weight-loss and glycemic efficacy at scale and to test whether elecoglipron reduces long-term cardiovascular and kidney events. No outcomes yet. | Source |
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Safety & Cautions
- Elecoglipron is an investigational medicine with no regulatory approval anywhere; it is not a supplement or research chemical, and any product sold as 'elecoglipron', 'AZD5004' or 'ECC5004' outside a regulated clinical trial is unverified and unsafe.
- Its long-term benefit is unproven: the 10.5-11.8% weight loss and 1.9% HbA1c reduction come from Phase 2b trials of 26-36 weeks, and whether elecoglipron reduces cardiovascular or kidney events - or matches injectable GLP-1 drugs over years - will not be known until the Phase 3 EMBOLD/ELUMINATE and outcome trials read out.
- As a GLP-1 receptor agonist it commonly causes gastrointestinal side effects (nausea, constipation, diarrhea, vomiting), mostly mild to moderate; GLP-1 class warnings around pancreatitis, gallbladder disease and (from rodent studies) thyroid C-cell tumors apply to the class and long-term human data for this molecule are still limited.
- Head-to-head superiority over semaglutide or tirzepatide has not been established; the SOLSTICE oral semaglutide comparison was an open-label exploratory arm, not a powered head-to-head test.
- It is being studied as a once-daily prescription-stage tablet under medical supervision; dosing, eligibility and escalation schedules are controlled within trials and it is not something to self-source or self-administer.
- Decisions about obesity or diabetes treatment should be made with a qualified clinician; this information is educational and not medical advice.
Comparisons
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Citations
- [1] Elecoglipron, an oral small molecule GLP-1 RA, moves to Phase III programme and unlocks next chapter in AstraZeneca's cardiometabolic and kidney portfolio (AstraZeneca press release, June 8, 2026) PubMed
- [2] Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA): a multicentre, phase 2, randomised, placebo-controlled clinical trial - The Lancet PubMed
- [3] Elecoglipron, an oral small molecule GLP-1 receptor agonist in adults with obesity or overweight (VISTA) - PubMed PubMed
- [4] ADA: AstraZeneca's oral GLP-1 shows 'competitive efficacy' and standard tolerability in phase 2 - Fierce Biotech PubMed
- [5] Elecoglipron Advances to Phase 3, Shows Phase 2 Weight Loss, Glycemic Data - HCPLive PubMed
- [6] Type 2 Diabetes: AstraZeneca's New Oral GLP-1 Led to 10.5% Weight Loss - Healthline PubMed
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