Highlights of this week center on the speed of clinical execution and the industry’s massive bet on oral therapeutics. Viking Therapeutics made headlines by completing enrollment for its Phase 3 obesity trial ahead of schedule, a signal that patient demand remains incredibly high and that challengers to the current duopoly are moving fast. Just to put this in perspective, the study start date was end of June 2025, and it already went above its enrollment target in less than six months!
However, the most significant long-term development might be on the oral front. Eli Lilly just registered a massive 7,000-patient cardiovascular outcomes trial for orforglipron. As I discuss in the Trial Spotlight, proving that a daily pill can deliver the same heart benefits as established injectables would be a pivotal differentiator in the cardiometabolic market.
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I also want to draw attention to the Mechanism Explained section this week. I take a look at “biased agonism” -- an engineering approach designed to maintain receptor activity for longer periods, which is becoming increasingly relevant as developers try to maximize the potency of oral formulations.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Viking completes Phase 3 enrollment for obesity drug VK2735.
Viking Therapeutics announced it has completed enrollment ahead of schedule for its Phase 3 VANQUISH-1 trial of subcutaneous VK2735, a dual GLP-1/GIP receptor agonist. The 78-week study enrolled approximately 4,650 adults with obesity or who are overweight and has a primary endpoint of percent change in body weight from baseline compared to placebo. The company expects to complete enrollment for its parallel Phase 3 VANQUISH-2 study in patients with type 2 diabetes in Q1 2026.
Oral Ecnoglutide Phase I/II evaluating the safety and tolerability of a tablet formulation in Chinese participants with overweight or obesity (Hangzhou Sciwind Biosciences, n=84)
Semaglutide Phase 4 investigating if the drug improves embryo quality in overweight and obese patients undergoing in vitro fertilization (IVF) (Fundacion Dexeus, n=62)
Maridebart Cafraglutide Phase I study assessing the drug’s effect on the heart’s electrical activity in healthy volunteers (Amgen, n=82)
[Weight Loss/Efficacy]
Trials: NCT07229157 | Mechanism: GLP-1 with novel mechanism
A Phase II trial combining an incretin mimetic with resistance exercise to improve cardiometabolic health in survivors of childhood ALL with obesity (St. Jude, n=20).
A Study of Orforglipron (LY3502970) on Cardiovascular Outcomes in Adults With Atherosclerotic Cardiovascular Disease and/or Chronic Kidney Disease (ATTAIN-Outcomes)
Eli Lilly’s ATTAIN-Outcomes trial is a landmark Phase 3 cardiovascular outcomes trial (CVOT) evaluating whether orforglipron, a once-daily oral non-peptide GLP-1 receptor agonist, can reduce the risk of major adverse cardiovascular events (MACE) compared to placebo. Enrolling approximately 7,140 participants with established atherosclerotic cardiovascular disease (ASCVD) or chronic kidney disease (CKD), this event-driven study will assess the drug’s ability to prevent heart attacks, strokes, and cardiovascular death over a multi-year horizon. Unlike oral semaglutide, which is a peptide requiring strict administration protocols (fasting), orforglipron is a small molecule designed for easier absorption and simpler dosing, potentially removing significant barriers to long-term adherence. This trial is strategically critical as it seeks to validate the first high-efficacy oral alternative to injectable blockbusters like Wegovy and Zepbound, potentially expanding access to cardioprotective GLP-1 therapy for millions of patients. While not yet recruiting, this trial is a critical component of a broad development program with other orforglipron studies expected to complete around 2026.
Ecnoglutide differentiates itself in the crowded metabolic landscape as an oral, long-acting GLP-1 receptor agonist with a specific “biased” signaling profile. Unlike standard agonists that trigger broad downstream effects, this molecule is engineered to preferentially stimulate cAMP production—the primary driver of insulin secretion and satiety—while minimizing β-arrestin recruitment. This selectivity is critical because β-arrestin typically promotes receptor internalization and desensitization; by avoiding it, the drug effectively keeps more receptors active on the cell surface for longer periods. Consequently, this approach aims to maximize therapeutic potency and duration, potentially allowing this oral tablet to rival the efficacy of established injectables like semaglutide. For the industry, ecnoglutide highlights a shift toward optimizing receptor dynamics to improve the therapeutic window and patient compliance in chronic weight management.
This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.
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