Drug: NNC0487-0111 (Amycretin)

Drug Type: Peptide GLP-1R/AMYR (Amylin Receptor) AgonistDeveloper: Novo Nordisk

Amycretin is a novel single-molecule drug that can simultaneously activate GLP-1 and amylin receptors, which exert a synergistic effect in regulating appetite and energy metabolism. The clinical data released this time is from a Phase 1b/2a randomized controlled trial, aiming to evaluate the safety, tolerability, pharmacokinetic properties, and weight loss effect of subcutaneous Amycretin in overweight or obese patients.

In the 36-week Part B trial, patients receiving weekly subcutaneous injections of 60 mg Amycretin achieved an average weight loss of 24.3%, with a placebo-adjusted weight loss effect of 23.2%; in contrast, the 20 mg dose group achieved a placebo-adjusted weight loss of 23.9% over the same period. Surprisingly, the efficacy of the 20 mg group was slightly superior to that of the 60 mg group.

Studies have shown that the safety and tolerability of Amycretin are consistent with the characteristics of GLP-1 and amylin agonists. The most common adverse events were gastrointestinal symptoms, including nausea, vomiting, and diarrhea, most of which were mild to moderate and resolved before the end of the study.

Drug: CagriSema

Drug Type: Dual-target Combined Injection FormulationDeveloper: Novo Nordisk

CagriSema (a combination of 2.4 mg semaglutide and 2.4 mg cagrilintide) developed by Novo Nordisk demonstrated significant weight loss efficacy in the Phase III REDEFINE 1 clinical trial. Data showed that at week 68, patients who persisted with treatment achieved an average weight loss of 22.7%, among which 97.6%, 40.4%, and 23.1% of patients achieved weight loss of ≥5%, ≥25%, and ≥30% respectively.

REDEFINE 1 mainly targeted obese or overweight adults without diabetes but with weight-related comorbidities. Results indicated that regardless of dose adjustment, CagriSema delivered significant and clinically meaningful weight loss, with a low discontinuation rate and good safety profile. The common adverse reactions were mild to moderate gastrointestinal symptoms.

Another study, REDEFINE 2, targeting patients with type 2 diabetes, also showed that the CagriSema group achieved an average weight loss of 15.7%. The REDEFINE program is currently ongoing, including the newly initiated REDEFINE 11 trial, which aims to further evaluate the long-term efficacy and safety of CagriSema. As a once-weekly subcutaneous injection drug, CagriSema is expected to become an important treatment option for obesity and metabolic diseases.

Drug: Wegovy

Drug Type: GLP-1 FormulationDeveloper: Novo Nordisk

Novo Nordisk announced positive results from the Phase 3b STEP UP trial, which evaluated the efficacy and safety of a higher dose of Wegovy® (7.2 mg semaglutide) in obese adults without diabetes. Data showed that at week 72, the 7.2 mg dose group achieved an average weight loss of 21%, with one-third of subjects losing ≥25% of their body weight, which was significantly superior to placebo and the currently approved 2.4 mg dose. Additionally, 93.2% of patients achieved weight loss of ≥5%. The safety and tolerability were consistent with existing doses, with the main adverse reactions being mild to moderate gastrointestinal responses and a low discontinuation rate.

Both the primary endpoint and key secondary endpoints of this study demonstrated that semaglutide 7.2 mg has significant advantages in weight loss efficacy, providing a new option for patients who have not achieved their weight loss goals. Novo Nordisk plans to submit a label update application for this dose to the European Union in the second half of 2025 and continue to advance the development of oral Wegovy.

The STEP UP trial enrolled 1,407 adults with a BMI ≥30 kg/m², verifying its superiority on top of lifestyle interventions. Meanwhile, the STEP UP T2D trial also confirmed the efficacy of this dose in obese patients with type 2 diabetes. These results further consolidate semaglutide's leading position as a GLP-1 receptor agonist in the field of obesity treatment.

Drug: LY3841136 (eloralintide)

Drug Type: Peptide AMYR AgonistDeveloper: Eli Lilly and Company

The published Phase I study (n=100) evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of eloralintide (4 doses, once-weekly subcutaneous injection) in obese or overweight subjects with a BMI of 27.0-43 kg/m². Studies showed that in the 12-week Phase I clinical study, the highest dose group achieved an average weight loss of 11.3%, while the low-dose group had an average weight loss of 2.6%. Although the efficacy of the low-dose group was limited, the data of the highest dose group reached the top level among similar early-stage studies, with significantly stratified weight loss outcomes. It also exhibited notable tolerability advantages over GLP-1 class drugs: the incidence of gastrointestinal adverse reactions was low (approximately 10% of patients experienced diarrhea and 8% had vomiting); overall adverse reactions were mostly mild, including decreased appetite and headache, with no serious safety events reported.

Drug: Bimagrumab

Drug Type: Fully Human Monoclonal Antibody Targeting Activin Type II Receptor (ActRII)Developer: Eli Lilly and Company

Eli Lilly and Company announced the results of the Phase IIb BELIEVE study of Bimagrumab at the 2025 ADA Scientific Sessions. This study aimed to evaluate its therapeutic effect as monotherapy or in combination with semaglutide in overweight or obese adults.

Results showed that after 72 weeks of treatment: the Bimagrumab + semaglutide combination group achieved a weight loss of 22.1%, significantly higher than 10.8% in the Bimagrumab (30 mg/kg) monotherapy group and 15.7% in the semaglutide (2.4 mg) monotherapy group;

In the Bimagrumab + semaglutide combination group for obese or overweight patients, 92.8% of the weight loss came from fat, significantly higher than 71.8% in the semaglutide monotherapy group. Notably, 100% of the weight loss in the Bimagrumab monotherapy group was from fat loss, and the Bimagrumab monotherapy group not only achieved 100% fat-derived weight loss but also increased lean body mass by 2.5%.

In terms of metabolism-related indicators, the combination therapy was superior to monotherapy in reducing visceral fat and lowering inflammatory markers such as hsCRP. In terms of safety, common side effects included muscle spasms, diarrhea, and acne.

Currently, among the global investigational ActRII pipelines, products that have entered Phase III or above have not been developed for weight loss indications, and Eli Lilly's drug is the most advanced in development.

Drug: efsitora alfa

Drug Type: Novel Basal InsulinDeveloper: Eli Lilly and Company

Eli Lilly and Company announced the Phase III clinical trial results of its once-weekly insulin formulation efsitora alfa (efsitora), including the QWINT-1, QWINT-3, and QWINT-4 studies. All trials met their primary endpoints: efsitora was non-inferior to once-daily basal insulin in reducing glycated hemoglobin (A1C) levels. The results of the three studies were presented at the 85th Scientific Sessions of the American Diabetes Association in 2025, with QWINT-1 published in the New England Journal of Medicine and QWINT-3 and QWINT-4 published in The Lancet.

QWINT-1 showed that in patients with type 2 diabetes using insulin for the first time, efsitora reduced A1C by 1.31% at week 52, compared with a 1.27% reduction with insulin glargine. Efsitora adopted a fixed-dose regimen adjusted once every four weeks, simplifying the treatment process. QWINT-3 and QWINT-4 evaluated patients who were already using basal or basal-plus-meal insulin; efsitora reduced A1C by 0.86% and 1.07% at week 26, respectively, which was comparable to the efficacy of insulin degludec and insulin glargine.

Researchers pointed out that as a once-weekly insulin treatment regimen, efsitora helps reduce hesitation in initiating insulin therapy, improves patient compliance and blood glucose management efficiency, and provides a more convenient treatment option for patients with type 2 diabetes.

Drug: Orforglipron

Drug Type: Oral Small-molecule GLP-1 Receptor AgonistDeveloper: Eli Lilly and Company

Eli Lilly and Company announced the results of the Phase III clinical ACHIEVE study of its oral GLP-1RA orforglipron, showing that all three doses of the drug met the primary endpoints.

Eli Lilly and Company released positive results from the Phase III clinical trial ACHIEVE-1 of its independently developed oral small-molecule GLP-1 receptor agonist orforglipron. The study evaluated the efficacy and safety of orforglipron in adult patients with type 2 diabetes who were either untreated or had poorly controlled blood glucose. Results showed that at week 40, all three dose groups (3 mg, 12 mg, 36 mg) significantly reduced glycated hemoglobin (A1C) by 1.3% to 1.6%, which was superior to placebo. Up to 76.2% of patients achieved the American Diabetes Association (ADA)-recommended A1C target of <7%, and some patients even returned to normal blood glucose levels. In addition, the 12 mg and 36 mg dose groups also achieved significant weight loss, with the highest dose group achieving an average weight loss of 16 pounds (approximately 7.9 kg). Adverse reactions were mainly mild to moderate gastrointestinal responses, consistent with GLP-1 class drugs.

As the first oral non-peptide GLP-1 receptor agonist that does not require fasting or water restrictions, orforglipron has the advantages of early onset and convenient use, and is expected to become an important oral drug for the treatment of type 2 diabetes. Currently, Eli Lilly is conducting longer-term ATTAIN series studies to comprehensively evaluate its potential in obesity and related metabolic diseases. Relevant results have been published in the New England Journal of Medicine and presented at the 85th ADA Scientific Sessions.

Drug: LAE102

Drug Type: ACVR2A (Activin Receptor Type IIA) Monoclonal AntibodyDeveloper: Luye Pharma (2105.HK)

Luye Pharma (2105.HK) announced the results of the Phase I single ascending dose (SAD) study of LAE102 (a monoclonal antibody targeting ActRIIA) for the treatment of obesity.

The data released by Luye Pharma this time is the first-in-human study data of its independently developed LAE102 in healthy subjects (abstract number 2205-LB), mainly evaluating its safety, tolerability, pharmacokinetics, and pharmacodynamics.

The study was divided into Part A (1.1/2/4/8/16 mg/kg, intravenous injection) and Part B (2/4/8 mg/kg, subcutaneous injection). Subjects were randomly assigned to the LAE102 group or the placebo group at a ratio of 6:2. Results showed that the serum concentration of LAE102 increased in a dose-dependent manner, exhibiting nonlinear PK and target-mediated drug exposure characteristics. A significant increase in serum activin A levels was observed in all dose groups. At the 28-day follow-up, activin A levels in the 8 mg/kg (subcutaneous injection) group, 8 mg/kg (intravenous injection) group, and 16 mg/kg (intravenous injection) group remained elevated.

In addition, single-dose LAE102 had good safety and tolerability; most treatment-emergent adverse events (TEAEs) were mild, asymptomatic laboratory abnormalities. No subjects reported serious adverse events or TEAEs leading to study termination. These data support further exploration of the potential of LAE102 (subcutaneous injection) in overweight or obese populations.

Drug: MSDC-0602K (azemiglitazone)

Drug Type: Small-molecule MPC InhibitorDeveloper: Metabolic Solutions Development/Cirius Therapeutics

MSDC-0602K is a next-generation oral insulin sensitizer targeting the mitochondrial pyruvate carrier (MPC), which may address these limitations. MSDC-0602K can selectively bind to MPC and regulate pyruvate entry into mitochondria.

Studies conducted in obese subjects with type 2 diabetes showed that both the MSDC-0602K monotherapy group and the group combined with tirzepatide had a decrease in the visceral:subcutaneous adipose ratio and an increase in brown adipose tissue. The adipose tissue of the combination group achieved deep remodeling. After 3 months of treatment, the insulin-mediated glucose metabolism in the MSDC-0602K monotherapy group increased by 50% (assessed by the euglycemic clamp technique), and intramyocellular lipids decreased by 50% (assessed by magnetic resonance spectroscopy).

Drug: NA-931 (bioglutide)

Drug Type: Oral Small-molecule IGF-1R/GLP-1R/GIPR/GCGR AgonistDeveloper: Biomed Industrie

At this conference, a total of three clinical research results of NA-931 were selected, two of which focused on weight loss indications.

NCT06564753: A 13-week Phase II randomized, double-blind, placebo-controlled, multiple ascending dose (MAD) study evaluated the safety, tolerability, and weight loss effect of once-daily oral NA-931 in adult subjects with obesity (BMI ≥30 kg/m²) or overweight (BMI ≥27 kg/m²) and at least one weight-related comorbidity. Results showed that weight loss in the NA-931 group was dose-dependent; among them, the 150 mg dose group had a 14.8% decrease from baseline, with a placebo-adjusted decrease of 13.2%. In an exploratory analysis, 72% of subjects in the NA-931 group achieved weight loss of ≥12%, compared with only 2% in the placebo group.

In terms of safety, it showed good performance; all gastrointestinal adverse events were non-significant or mild reactions. Subjects in the NA-931 group reported mild nausea and vomiting, and 8.1% experienced diarrhea, compared with 3.2% in the placebo group. No muscle loss was observed.

NCT06615700: A 28-day Phase I randomized, double-blind, placebo-controlled, dose-escalation study (n=74) evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of NA-931 after single and multiple ascending dose administrations in overweight or obese subjects. Data showed that NA-931 exhibited a dose-dependent weight loss trend during treatment, with the maximum weight loss of up to 6.4%. In the dose groups ≥60 mg, the weight loss effect was maintained at day 35 (7 days after the last dose), with a maximum placebo-adjusted weight loss of 5.3%. Exploratory analysis showed that 63% of subjects in the NA-931 group achieved weight loss of ≥5%, compared with 0% in the placebo group.

In terms of safety, NA-931 was generally well-tolerated, and treatment-related adverse events (TEAEs) were mostly non-significant or mild. No nausea or vomiting of mild or higher severity was reported; 1 case (2.3%) in the NA-931 group and 2 cases (10%) in the placebo group experienced diarrhea. Similarly, no muscle loss was observed.

Drug: ZP7570 (dapiglutide)

Drug Type: Peptide GLP-1R/GLP-2R AgonistDeveloper: Zealand Pharma

The published Phase Ib clinical trial (n=54) evaluated the safety, tolerability, pharmacokinetics, and pharmacodynamics of once-weekly subcutaneous dapiglutide in healthy subjects with a BMI of 27.0–39.9 kg/m². Subjects were randomly assigned to the dapiglutide group (doses of 7.5 mg, 10 mg, and 13 mg) or the placebo group at a ratio of 14:4, and the dose was escalated every two weeks during the 13-week treatment period to gradually reach the target dose. No additional lifestyle interventions were performed on the subjects during the trial.

Results showed that after 13 weeks, the body weight of the placebo group increased by 2.1%. After placebo adjustment, the body weight of the 7.5 mg, 10 mg, and 13 mg dose groups decreased by 6.7%, 8.3%, and 7.1%, respectively, showing a good weight loss trend.

Pharmacokinetic data showed that dapiglutide had a dose-proportional relationship, and the average half-life of the three dose groups was 112–119 hours, supporting its once-weekly dosing regimen. In addition, 14.3% of subjects in the dapiglutide group were detected with low-titer anti-drug antibodies (ADA) during follow-up, but these antibodies did not have a significant impact on pharmacokinetics, efficacy, or safety.

In terms of safety, dapiglutide generally performed well; no treatment-related serious or severe adverse events were reported. The most common adverse reactions were gastrointestinal disorders and metabolic and nutritional disorders (mainly manifested as decreased appetite), most of which were mild. Only 2 subjects withdrew from the trial due to gastrointestinal adverse events.

Drug: CK-0045

Drug Type: IL-22 AnalogueDeveloper: Cytoki Pharma

The published Phase I clinical trial evaluated the safety, tolerability, and pharmacokinetic characteristics of CK-0045 in healthy subjects (both obese and non-obese populations). In the single ascending dose (SAD) part, 40 healthy subjects were randomly assigned to 5 cohorts at a ratio of 3:1, receiving a single subcutaneous injection of CK-0045 (dose range of 1–30 µg/kg) or placebo. In the multiple ascending dose (MAD) study, 36 obese healthy subjects (BMI of 30.0-39.9 kg/m²) were also randomly grouped at a ratio of 3:1, receiving once-weekly CK-0045 (1.25, 2.5, or 5 µg/kg) or placebo for 6 weeks.

Results showed that CK-0045 exhibited good safety at all doses and was well-tolerated at doses up to 10 µg/kg in the SAD part and 2.5 µg/kg in the MAD part.

All adverse events were mild or moderate; the most common drug-related adverse events included dry skin, dry lips, and pruritus. No clinically significant abnormalities in electrocardiograms, laboratory tests, or vital signs were observed.

In addition, CK-0045 also showed a significant cholesterol-lowering effect, and potential improvement trends were observed in multiple other metabolic indicators.

Drug: ZP8396 (petrelintide)

Drug Type: Amylin AnalogueDeveloper: Zealand/ Roche Global R&D

The published Phase I clinical trial (n=48) evaluated the weight loss effect of once-weekly subcutaneous petrelintide in overweight or obese healthy subjects. Baseline data of the study showed that the average BMI of the subjects was 29 kg/m², the average body weight was 92 kg, and the average waist circumference was 102 cm. Subjects were randomly assigned to the petrelintide treatment group (doses of 2.4 mg, 4.8 mg, and 9.0 mg) or the placebo group at a ratio of 3:1, receiving 16 weeks of treatment.

Results showed that in terms of weight loss, the three dose groups of petrelintide achieved weight loss of 4.8%, 8.6%, and 8.3%, respectively, while the combined placebo group had a weight loss of 1.7%; in terms of waist circumference change, the petrelintide groups had reductions of 5.0 cm, 7.2 cm, and 7.6 cm, respectively, compared with only 1.9 cm in the placebo group. Notably, female subjects had a more pronounced treatment response in all dose groups.

Petrelintide was generally well-tolerated, with a low incidence of gastrointestinal adverse events, most of which were mild to moderate. Only 1 subject withdrew from treatment due to gastrointestinal adverse reactions.

Image Source: ADA official website

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