The GLP-1 Lilly Isn’t Aiming at Obesity
Week Of July 4 – July 10, 2026
Eli Lilly is running a tirzepatide-class GLP-1/GIP drug through Phase 3 trials for depression and alcohol use disorder, Phase 2 for schizophrenia, asthma, and irritable bowel syndrome, and only Phase 1 for obesity. In the Trial Spotlight, I go into brenipatide and Lilly’s RENEW program: a weight-loss-class molecule being tested for depression, addiction, and asthma, with obesity its least-advanced use. In the Mechanism Explained, I cover where GLP-1 and GIP receptors turn up beyond metabolism, in the brain’s reward and mood circuits, the immune system, the lung, and the gut, and why that has companies testing an incretin in conditions like depression and asthma. Also this week: Dr. Reddy’s pauses its generic semaglutide over a manufacturing issue, and Novo partners on an ultra-long-acting semaglutide implant.
Some interesting things I was reading recently pointed to how quickly the GLP-1 market is broadening across both access and product form. This New York Times piece on older adults as Medicare coverage expands was a useful reminder that wider access brings a different set of clinical questions around muscle loss, dehydration, and long-term use, while Fierce Pharma’s oral GLP-1 tracker is a good way to watch the shift from injections to pills, an early race in which Lilly’s Foundayo is off to a muted start. I also found Endpoints’ report on BrightGene’s obesity shot nearing approval in China interesting as another sign that the next wave of GLP-1 competition may be increasingly global, a shift echoed in this week’s Press section, where Hengrui’s oral GLP-1 cleared its Phase 3 weight-loss goals in China.
🔥 THIS WEEK’S KEY DEVELOPMENTS
Dr. Reddy’s pauses generic semaglutide supply over an API specification failure
Dr. Reddy’s announced it will delay commercial supplies of its generic semaglutide, which has launched in India and Canada. The delay is due to an issue with the active pharmaceutical ingredient (API) that caused some batches to be “out of specification.” The company stated there is no impact on patient safety or on the product’s existing global regulatory filings.
Press | Mechanism: GLP-1 receptor agonist
Novo Nordisk partners with Vivani Medical on long-acting GLP-1 implant NPM-139
Novo Nordisk has entered into an agreement with Vivani Medical to evaluate NPM-139, a miniature, ultra long-acting semaglutide implant for chronic weight management. Vivani is set to initiate a first-in-human Phase 1 study of the implant in the coming weeks, using Wegovy injections as an active comparator. The agreement, which utilizes Vivani’s NanoPortal platform technology, has no exclusivity provisions for Novo Nordisk.
Press | Mechanism: GLP-1
Kalohexis files for IPO to advance GLP-1 obesity challenger.
Kalohexis, a spinout from Endevica Bio, announced on July 7 that it has confidentially submitted IPO documents to the Securities and Exchange Commission to support its obesity and cancer cachexia treatments. The company’s lead assets are 710GO, an oral dual MC3R/MC4R agonist in Phase 1 development for weight loss, and mifomelatide, an injectable dual MC3R/MC4R antagonist in Phase 2 for cancer cachexia.
Press | Mechanism: MC3R/MC4R agonist
📰 PRESS
Hengrui’s oral GLP-1 meets Phase 3 weight loss goals in China.
Press | Mechanism: GLP-1 receptor agonist
MindRank raises $52M for Phase 3 oral GLP-1 drug.
Press | Mechanism: GLP-1 receptor agonist
Ascletis submits two FDA INDs for once-monthly obesity drugs.
Press | Mechanism: amylin receptor agonist
💡 TRIAL SPOTLIGHT
Educational spotlight selected by editors
A GLP-1 Drug That Isn’t Chasing Weight Loss: Inside Lilly’s RENEW Program
Eli Lilly’s brenipatide (LY3537031) is an internally discovered, unimolecular dual agonist of the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors, but unlike its class sibling tirzepatide, it is being directed almost entirely outside of obesity. Engineered for once-monthly subcutaneous injection rather than weekly dosing, the molecule is advancing through a coordinated clinical program named RENEW that targets neuropsychiatry, addiction, gastrointestinal, and respiratory indications. The program recently signaled a clear escalation toward pivotal execution when six RENEW trials added approximately 190 clinical sites in a single week, supporting Phase 3 studies in major depressive disorder and alcohol use disorder alongside Phase 2 trials for schizophrenia, bipolar disorder, smoking, opioid use disorder, irritable bowel syndrome, and asthma. While brenipatide is being tested in healthy volunteers with overweight or obesity, these are strictly Phase 1 clinical pharmacology and multiple-ascending-dose studies serving as routine safety, tolerability, and dose-finding anchors required for any incretin development, with no Phase 2 or Phase 3 weight-loss trials underway.
Although Lilly has not publicly explained this strategy, the most credible analytical inference is portfolio diversification into GLP-1 brain and immune biology, given that Lilly already possesses a saturated obesity pipeline featuring tirzepatide, the oral pill orforglipron, and the triple agonist retatrutide, whereas a monthly dosing schedule could plausibly benefit adherence-challenged chronic populations. Reinforcing this strategic shift into immunology and inflammation, Lilly Chief Scientific Officer Dan Skovronsky highlighted brenipatide in the context of a Phase 2 asthma study during a February 2026 earnings call, framing the molecule as an expansion of the mechanism into new therapeutic domains ahead of initial clinical readouts expected around 2027.
ClinicalTrials.gov: NCT07412756 (RENEW-MDD 1, Phase 3 major depressive disorder) | NCT07219966 (RENEW-ALC-1, Phase 3 alcohol use disorder) | NCT07219173 (Phase 2 asthma) | NCT07476118 (Phase 1b obesity pharmacology)
🔬 MECHANISM EXPLAINED
Understanding the science behind the therapeutics
Beyond the Pancreas: Why the Tirzepatide Receptor Class Is Being Tested for Depression, Asthma, and Addiction (Example drugs: Brenipatide)
While glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are incretin hormones best known for stimulating insulin and suppressing appetite, their receptors are expressed far beyond the pancreas and hypothalamic appetite centers, anchoring the expansion of dual agonists like Eli Lilly’s brenipatide into current trials for depression, addiction, irritable bowel syndrome, and asthma. In the brain, GLP-1 receptors populate the ventral tegmental area, nucleus accumbens, prefrontal cortex, hippocampus, and amygdala, while GIP receptors are co-expressed in the hypothalamus. Preclinical models show that agonism dampens dopamine signaling in the ventral tegmental area to nucleus accumbens reward pathway, reducing seeking across alcohol, nicotine, cocaine, and opioid models to provide the rationale for alcohol use disorder, smoking, and opioid use disorder trials. This central activity also attenuates neuroinflammation and oxidative stress, enhances hippocampal neurogenesis and neuroplasticity, and modulates serotonergic and noradrenergic signaling, forming the biological basis for depression, bipolar, and schizophrenia trials.
Peripherally, the GLP-1 receptor sits on immune cells including macrophages, monocytes, eosinophils, and lymphocytes to inhibit nuclear factor kappa B signaling and lower pro-inflammatory cytokines such as tumor necrosis factor alpha and interleukin 6, acting partly through a gut-to-brain axis that suppresses peripheral inflammation. In mucosal tissues, its expression on pulmonary epithelial cells regulates airway inflammation, while its presence within the enteric nervous system and myenteric plexus on vagal afferent nerves modulates gut motility and secretion, providing the mechanistic rationale for asthma and irritable bowel syndrome trials. The unifying idea is that the exact same biology that suppresses appetite also touches reward, mood, inflammation, and gut and airway physiology, explaining why a single receptor class is spreading across neuropsychiatry, addiction, immunology, and gastroenterology at once. However, human clinical proof in these non-metabolic indications does not yet exist, and ongoing trials with readouts expected around 2027 will ultimately determine if this preclinical receptor pharmacology translates into established clinical benefit.
🆕 NEWLY REGISTERED TRIALS (7 in last week)
BI 3034701 Phase I evaluating safety and tolerability in Japanese healthy volunteers and individuals with obesity or overweight (Boehringer Ingelheim, n=48)
[Weight Loss/Efficacy]
Trials: NCT07693231 | Mechanism: Triple GLP-1/GIP/Y2 agonist
Efsubaglutide Alfa Phase Ib trial investigating the injection as a potential treatment for obese adolescents (Shanghai Yinnuo Pharmaceutical Technology, n=36)
[Weight Loss/Efficacy]
Trials: NCT07693426 | Mechanism: GLP-1 receptor agonist
HRS-4729 Phase 2 trial investigating the efficacy and safety of the injection for treating obesity (Fujian Shengdi Pharmaceutical, n=252)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07690826 | Mechanism: Triple GLP-1/GIP/glucagon agonist
MARITIME-1-EXTENSION Phase 3 long-term extension trial evaluating the safety and efficacy of Maridebart Cafraglutide for obesity (Amgen, n=3200)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07684235 | Mechanism: GLP-1 agonist / GIP antagonist
MARITIME-2-EXTENSION Phase 3 long-term extension study of Maridebart Cafraglutide, assessing continued safety and efficacy in obesity (Amgen, n=950)
[Weight Loss/Efficacy | Safety/Tolerability]
Trials: NCT07684144 | Mechanism: GLP-1 agonist / GIP antagonist
Petrelintide Phase 1 studying pharmacokinetics in participants with impaired hepatic function (Zealand Pharma, n=36)
[Safety/Tolerability]
Trials: NCT07682818 | Mechanism: Amylin receptor agonist
Olatorepatide Phase 2 trial evaluating the drug in adults with overweight or obesity who do not have diabetes (Regeneron Pharmaceuticals, n=360)
[Weight Loss/Efficacy]
Trials: NCT07685808 | Mechanism: Dual GLP-1/GIP agonist
This newsletter compiles publicly available information from press releases, news sources, and trial registries. Not investment advice.
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