More Than Body Fat Reduction
WEEK OF OCTOBER 18 – OCTOBER 24, 2025
One of the things that has struck me since starting to follow the GLP-1/incretin space is the expansion of indications for these medicines. Understanding how the medicines exert their effects is a fascinating area of study, and there were related updates this week. The Lancet reported an analysis of the Novo Nordisk-sponsored SELECT clinical trial testing semaglutide’s effects on heart disease and stroke in patients with overweight or obesity. The original results (a significant reduction in major adverse cardiovascular events) were reported in 2023 when the trial was complete and ultimately led to an FDA approval for a new indication. The new analysis in The Lancet showed that the reduction in body fat could only explain about a third of the effect on cardiovascular events. How does it work then? People are not sure, but a reduction in inflammation is one of the hypothesized mechanisms.
The Trial Spotlight this week (see below) also showcases the theme of using GLP-1s for indications other than obesity.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Novo Nordisk presents new obesity data on oral semaglutide, CagriSema.
Novo Nordisk announced it will present 23 abstracts at ObesityWeek® 2025 from November 4-7, featuring new data on investigational oral semaglutide 25 mg and its obesity pipeline. Key presentations will include a post-hoc analysis from the OASIS 4 trial on oral semaglutide 25 mg’s effect on glycemic parameters and cardiovascular risk factors. The company will also present new data for investigational CagriSema from the REDEFINE 1 trial, including analyses on its cardiovascular risk reduction potential.
Press | Trials: NCT05564117 | NCT05567796 | NCT05646706 | Mechanism: Semaglutide is a GLP-1 agonist; CagriSema is a GLP-1 agonist plus a dual amylin and calcitonin receptor agonist
Viking reports positive Phase 2 data for oral weight loss drug VK2735.
Viking Therapeutics announced its Phase 3 VANQUISH program for subcutaneous VK2735 is proceeding on schedule, with enrollment for the VANQUISH-1 study expected to complete by the end of 2025 and VANQUISH-2 in Q1 2026. The company also reported positive top-line results from its Phase 2 VENTURE-Oral Dosing study, where the oral tablet formulation of VK2735 demonstrated up to 12.2% mean weight loss after 13 weeks. A Phase 1 maintenance dosing study is now underway to evaluate various regimens, with results expected in mid-2026.
Press | Trials: NCT07104383 | NCT07104500 | NCT06068946 | NCT06828055 | Mechanism: dual agonist of the GLP-1 receptor and the GIP receptor
Viking initiates maintenance dosing study for obesity drug VK2735.
Viking Therapeutics has initiated a Phase 1 exploratory maintenance dosing study of its dual GLP-1/GIP agonist, VK2735, in approximately 180 adults with obesity. Following an initial 19-week period of weekly subcutaneous VK2735, participants will be transitioned to various maintenance regimens including monthly subcutaneous, daily oral, or weekly oral doses until Week 31. The study will evaluate safety, tolerability, and changes in body weight, with results expected in 2026.
Press | Trials: not yet in the US clinical trials registry | Mechanism: dual agonist of the GLP-1 receptor and the GIP receptor
PRESS RELEASES
• Altimmune to present Phase 2b pemvidutide MASH data at AASLD. Press | Trials: NCT05989711 | Mechanism: GLP-1/glucagon dual receptor agonist
🆕 NEWLY REGISTERED TRIALS (5 in last week)
Tirzepatide Phase 2 trial investigating its potential to slow biological aging (The University of Texas Medical Branch, Galveston, n=90)
[New Indications]
Trials: NCT07220473 | Mechanism: Dual GLP-1/GIP agonist
RESOLVE-2 Phase 2 trial investigating NT-0796 as an adjunct therapy to semaglutide for participants with obesity (NodThera Limited, n=80)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07220629 (RESOLVE-2) | Mechanism: Non-incretin mechanism
Brenipatide Phase 2 trial evaluating the drug as a treatment for adults with uncontrolled moderate to severe asthma (Eli Lilly, n=531).
[New Indications]
Trials: NCT07219173 | Mechanism: Dual GLP-1/GIP agonist
Tirzepatide Phase IV investigating effects on menopausal vasomotor symptoms and biological aging in post-menopausal women with obesity (Mayo Clinic, n=40)
[Weight Loss/Efficacy]
Trials: NCT07218445 | Mechanism: Dual GLP-1/GIP agonist
Semaglutide Phase 3 trial investigating if the GLP-1 agonist can reduce or stop alcohol consumption in U.S. Veterans with Alcohol Use Disorder (VA Office of Research and Development, n=438).
[Safety/Tolerability]
Trials: NCT07218354 (CRAVE) | Mechanism: GLP-1 receptor agonist
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
A Study to Evaluate Brenipatide Compared With Placebo in Adult Participants With Uncontrolled Moderate to Severe Asthma
Eli Lilly is launching a Phase 2 trial to investigate brenipatide, a novel dual GLP-1/GIP agonist, for adults with uncontrolled moderate-to-severe asthma. This 52-week, randomized, placebo-controlled study will assess if this new mechanism can benefit patients who remain symptomatic despite standard therapies. While widely used for diabetes and obesity, this drug class is being explored in asthma due to the presence of GLP-1 receptors in the lungs, where they may exert anti-inflammatory and immunomodulatory effects. With enrollment targeted at 531 participants, the trial represents a significant strategic step, testing a completely new pathway beyond traditional inhaled corticosteroids or biologics to address the underlying drivers of severe asthma. Success would introduce a systemic, metabolism-based approach to treating a respiratory disease where significant unmet needs persist.
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
Quadruple Agonism for Weight Loss (Example drug: NA-931)
NA-931 (Bioglutide™) represents a novel approach to weight management by functioning as an oral quadruple receptor agonist, simultaneously activating the GLP-1, GIP, glucagon, and IGF-1 receptors. This multi-faceted mechanism aims to induce weight loss through the established incretin pathways of GLP-1 and GIP, which regulate appetite and glucose metabolism, while also leveraging glucagon’s role in increasing energy expenditure. The addition of IGF-1 receptor agonism is a key differentiator, intended to preserve muscle mass during weight loss, a common concern with existing incretin-based therapies. In a competitive landscape dominated by injectable dual GLP-1/GIP agonists like tirzepatide, NA-931’s oral administration and unique quadruple-action mechanism, particularly its muscle-sparing potential, could offer a significant clinical advantage. This approach seeks to provide a more comprehensive metabolic modulation, potentially leading to higher quality weight loss and improved patient convenience.
This newsletter compiles publicly available information from company press releases and ClinicalTrials.gov. Not investment advice.