New data and analyses presented at the American Diabetes Association’s annual meeting highlight the priorities for the next generation of weight loss medicines: muscle preservation, limited side effects and novel targets.
Despite not being in the event name, weight loss and obesity took center stage at the recently concluded 2025 Scientific Sessions of the American Diabetes Association.
That much isn’t surprising. Obesity is the hottest thing going in biopharma, so much so that analysts now expect the market to hit an eye-watering $150 billion annually by the early 2030s.
Next-generation approaches are expected to play a key role, and they were on full display at ADA, with many of the biggest presentations focusing on ways to improve on existing treatments through safer regimens, more convenient dosing and even new pathways to elicit greater weight loss.
“What’s missing from the obesity space is a stronger focus on patient experience—specifically ease of use, accessibility, and preserving muscle mass,” John Gagliano, senior director at BioPharmCatalyst, told BioSpace in an email.
Despite existing drugs’ efficacy in cutting body weight, many patients are still discouraged from taking them, Gagliano said, because of “frequent injections, concerns about weakness, or unwanted muscle loss.” Companies in this space, he added, would do well to “prioritize lifestyle-friendly treatments.”
Samuel Redfern, associate analyst of pharmaceuticals at BMI, a FitchSolutions Company, agreed, telling BioSpace in an email that while patients discontinue weight loss treatment for a variety of reasons, “gastrointestinal side-effects and muscle loss are key drawbacks of existing GLP-1 therapies.” Exploring new mechanistic pathways, such as targeting amylin or preserving muscle, he continued, could result in new treatments that are as effective but do not have these drawbacks, allowing them to “drive long-term growth” in this space.
Biopharma is on the case, and several companies showcased their most recent developments at ADA last month.
Weight loss leaders Novo Nordisk and Eli Lilly provided updates on CagriSema and orforglipron, respectively, both of which have been positioned as successors to these companies’ current blockbuster franchises. The conference also saw presentations from other obesity players, including Amgen on its GLP-1/GIP analog MariTide and Innovent on its GLP-1/glucagon dual agonist mazdutide.
Here, BioSpace peers further into the future of the obesity space.
Lilly’s Bimagrumab Preserves Muscle in Mid-Stage Trial
El Lilly’s oral GLP-1 agonist orforglipron stole the spotlight at ADA 2025 for good reason: The drug recently cleared a Phase III diabetes trial, where it showed “injectable-like efficacy,” according to analysts at BMO Capital Markets. Another readout, this time in obesity, is slated for the third quarter.
But just as compelling is the pharma’s bimagrumab, a mid-stage antibody that targets activin/myostatin type II receptors, which are involved in signaling cascades that counteract muscle growth. Bimagrumab’s mechanism not only prevents muscle loss but can also promote an increase in muscle.
Lilly presented data from the Phase IIb BELIEVE trial at ADA, demonstrating that bimagrumab, when used with rival Novo Nordisk’s blockbuster GLP-1 drug Wegovy (semaglutide), can lower body weight by 22.1% at 72 weeks. Notably, 92.8% of this weight loss is attributable to fat—only around 7% was due to the wasting of lean mass.
Participants who were given bimagrumab alone lost 10.8% of their body weight at 72 weeks, 100% of which was due to fat loss.
These data could position bimagrumab well for the future weight-loss treatment space envisioned by Redfern, where “cornerstone” treatments like Lilly’s Zepbound (tirzepatide) and Wegovy will be “used in combination with new mechanisms of action that mitigate their less desirable effects.”
Analysts at BMO Capital Markets are similarly optimistic about bimagrumab. Writing to investors on June 23, they called the candidate’s performance in BELIEVE “robust” and “impressive,” with its weight loss numbers providing a “clear positive for building a regulatory approval case for body composition assets.”
Not all are convinced, however. Leerink Partners in a June 24 note expressed concern about “multiple tolerability/safety flags in the data,” adding that high rates of muscle spasms, diarrhea and acne alongside elevated levels of low-density lipoprotein cholesterol and liver enzymes “cloud bimagrumab’s overall profile and make commercial prospects unclear.”
“We continue to model zero sales for bimagrumab,” the analysts wrote.
Novo Fights For Amylin Lead With Amycretin—But Data Remain Mixed
Amylin, a pancreatic peptide that lowers blood sugar levels and suppresses appetite, has recently become a contested frontier in the weight loss space. With the late-stage CagriSema, a combination regimen consisting of semaglutide and the long-acting amylin mimetic cagrilintide, Novo is arguably at the head of the pack.
But CagriSema has run into its fair share of troubles: A December 2024 Phase III readout fell short of expectations, sparking a selloff that wiped some $72 billion off the pharma’s market cap.
In a bid to maintain its amylin lead—and regain some investor confidence—Novo is now looking to move its next-generation therapy amycretin quickly through the clinic. The drug, which also targets both GLP-1 and amylin, elicited weight loss of up to 22% after 20 weeks when given as a 20-mg subcutaneous dose in a Phase Ib/IIa trial, Novo reported in January.
Reacting to these results, BMO analysts at the time said that amycretin “could start to shift the narrative around Novo shares with a next-gen therapy in the company’s pipeline that could be competitive with the likes of Lilly’s tirzepatide and retatrutide.”
Novo released follow-on data at ADA, noting that after 36 weeks of treatment with doses as high as 60 mg, patients saw a 24.3% reduction in weight. This dipped slightly to 23.2% after correcting for placebo.
Still, analysts remain tempered in their optimism over amycretin. Reacting to Novo’s ADA presentation, William Blair told investors in a June 23 note that while amycretin’s 36-week weight loss was impressive, “the high frequency of adverse events could fuel uncertainty over the asset’s differentiation against approved or late-stage investigational compounds.”
Nevertheless, Novo appears committed to its next-generation amylin asset, announcing at ADA that it will take both subcutaneous and oral formulations of amycretin “straight to phase 3 development for weight management.” The pharma will launch its late-stage program for amycretin in the first quarter of 2026.
Zealand Targets Two GLP Receptors to Address Underlying Obesity Inflammation
Zealand Pharma is looking to innovate on the current GLP-1 approach to obesity by adding a molecular cousin into the mix: GLP-2.
At ADA, the Danish biotech touted Phase Ib data for its investigational subcutaneous injection dapiglutide, which activates both the GLP-1 and GLP-2 receptors. This unique mechanism of action—one Zealand claims is potentially first-in-class—allows dapiglutide to not only elicit the usual metabolic benefits of GLP-1 agonists, but also address low-grade inflammation linked to the GLP-2 pathway.
In a June 19 note to investors, analysts at William Blair noted that the involvement of GLP-2 could be “particularly beneficial” for dapiglutide, giving it the potential to address conditions adjacent to obesity, such as cardiovascular disease, leaky gut, liver disease and neurological inflammation.
“Zealand is positioning dapiglutide as a therapy that could both induce weight loss and potentially reduce the risk of obesity-related health outcomes, which we argue could have a more meaningful public health implication,” William Blair wrote.
In its ADA readout, Zealand touted weight loss of 11.6% over 28 weeks of observation, a figure William Blair argued might be an underrepresentation of dapiglutide’s true efficacy.
William Blair, in its note, flagged the “atypical” characteristics of Zealand’s study sample. More than 90% of the participants were male, for instance, and had a “relatively low baseline body weight” of approximately 92 kg. When tested in a “more representative population”—as in a sample with a more balanced sex split or in people who are overweight or obese at baseline—dapiglutide could show even higher weight loss numbers, the analysts said.
According to its Q1 report, Zealand expects to initiate a Phase II trial of dapiglutide this year.
Scholar Rock’s SMA Drug Shows Muscle-Preserving Potential in Obesity
Like Lilly, Scholar Rock is working to improve the quality of weight loss by preserving lean mass. Unlike Lilly, the Massachusetts-based biotech is focusing on just one muscle molecule: myostatin.
Part of the TGFβ superfamily of growth factors, myostatin is a signaling protein that suppresses the development of skeletal muscles. Apitegromab targets both active and latent forms of myostatin, a mechanism of action that could lead to “healthier weight loss” in patients on obesity medications, Akshay Vaishnaw, president of R&D at Scholar Rock, said in a June 18 release.
Olivia Tidwell, content coordinator at BioPharmCatalyst, agreed. “While most obesity treatments focus on total weight loss, apitegromab uniquely addresses the preservation of lean muscle mass—a growing concern with GLP-1 therapies like tirzepatide, which can cause significant muscle loss,” she told BioSpace. “Apitegromab offers a differentiated approach with potential value in a broad cardiometabolic population.”
Data presented at ADA, from the Phase II EMBRAZE trial, showed that over 24 weeks of treatment, patients treated with both apitegromab and Lilly’s trizepatide lost 3.4 lbs of lean mass, as opposed to 7.6 lbs in those given tirzepatide alone. The difference of 4.2 lbs represented a nearly 55% muscle preservation advantage in the apitegromab arm, Scholar Rock announced at the time.
EMBRAZE found apitegromab to be safe and well-tolerated, with adverse events arising comparably between treatment arms. There were no serious adverse events or study dropouts related to apitegromab, and no patient deaths.
The candidate also had a clean safety profile, Jefferies wrote, “which is one of the key advantages of more selectively targeting latent myostatin vs broadly targeting myostatin + activin A.”
Scholar Rock’s lead indication for apitegromab is spinal muscular atrophy (SMA), a genetic neuromuscular disorder. Apitegromab is currently undergoing regulatory review in this indication, with a verdict expected on Sept. 22. An SMA approval would be a “major de-risking event” for apitegromab, Jefferies noted.
Terns Targets Thyroid Hormone Receptors
Closing out this list is an asset that wasn’t featured at ADA but nevertheless offers a novel approach to obesity: Terns Pharmaceuticals’ THR-β agonist TERN-501.
TERN-501 works by activating the beta subtype of the thyroid hormone receptor (THR), which plays a key role in regulating several metabolic processes. Though not as extensively studied as GLP-1, the THR pathway also presents a promising target for obesity treatment, with several studies showing that agonists to this receptor can help control lipid and cholesterol levels while also boosting metabolic rate.
However, THR modulators have also been linked to cardiovascular complications, which limit their use in managing body weight. This is where Terns is looking to distinguish itself. According to the biotech’s website, TERN-501 is designed to be especially selective for THR-β, with enhanced distribution in the liver—a claim backed by preclinical data demonstrating a 23-fold greater selectivity for this specific subtype of the receptor compared with the THR-α subtype. This selectivity “[minimizes] the risk of cardiotoxicity and other off-target effects,” according to Terns.
In June 2024, the biotech released preclinical data demonstrating that when used with Novo’s semaglutide, TERN-501 can elicit significantly greater weight loss in mouse models as compared with semaglutide alone. Weight reduction appeared to be largely attributable to fat loss: patients treated with TERN-501 plus semaglutide saw a significantly greater decrease in fat mass versus comparators on semaglutide alone.
