ADA 2026 data from the Phase 3 DREAMS-3 trial show mazdutide delivered greater HbA1c reductions, weight loss, and metabolic benefits than semaglutide.
Written By: Samiksha Jadhav, BPharm
Reviewed By: Pharmacally Editorial Team
New data presented at the ADA 2026 Scientific Sessions expand on previously reported Phase 3 DREAMS-3 topline results, offering a detailed assessment of mazdutide’s efficacy and safety versus semaglutide in adults with T2D and obesity. The findings showed superior reductions in HbA1c and body weight with the dual GCG/GLP-1 receptor agonist, along with improvements in several cardiometabolic risk markers.
Trial Design and Comparator Context
The multicenter, open-label DREAMS-3 (NCT06184568) study randomized 329 Chinese adults with inadequately controlled T2D and obesity to receive mazdutide 6 mg or semaglutide 1 mg for 32 weeks. Baseline HbA1c averaged 8.02%, while mean body weight was 90.5 kg.
Semaglutide was evaluated at its approved diabetes dose of 1 mg rather than the higher 2.4 mg obesity dose. At week 32, 48.0% of patients receiving mazdutide achieved both HbA1c below 7.0% and at least 10% weight loss, compared with 21.0% of those receiving semaglutide, more than doubling the achievement rate.
Superior Glycemic and Weight Outcomes
Mazdutide produced statistically significant improvements across key efficacy endpoints. Mean HbA1c declined by 2.03% from baseline compared with 1.84% for semaglutide (p<0.05). Mean body weight decreased by 10.3% versus 6.0%, respectively (p<0.0001).
The dual agonist also achieved higher rates of clinically meaningful weight loss. At week 32, 80.6% of patients achieved at least 5% weight loss and 51.2% achieved at least 10% weight loss, compared with 52.8% and 21.3% in the semaglutide group. Improvements extended to waist circumference, fasting glucose, blood pressure, and lipid parameters, indicating broader cardiometabolic benefits beyond glucose control and weight reduction.
Dual Mechanism for Diabesity
Mazdutide combines GLP-1 receptor agonism, which enhances insulin secretion, lowers blood glucose, and suppresses appetite, with glucagon receptor activation, which promotes fat oxidation and increases energy expenditure. This dual mechanism supports comprehensive metabolic management in patients living with both diabetes and obesity.
The need remains substantial. Approximately 70 million adults in China have both T2D and overweight or obesity, increasing the risk of cardiovascular, renal, retinal, and other long-term complications.
Safety Profile Consistent with Prior Studies
Mazdutide demonstrated a safety profile consistent with previous clinical studies. Gastrointestinal adverse events, including nausea, diarrhea, and vomiting, were the most frequently reported events. These were generally mild to moderate, transient, and occurred primarily during dose escalation.
Treatment discontinuations remained low, and investigators reported no severe hypoglycemia or new safety signals.
Implications for Diabesity Management
Professor Linong Ji of Peking University People’s Hospital said DREAMS-3 demonstrated superior glucose lowering and weight reduction compared with semaglutide while also improving cardiometabolic risk factors, supporting a more integrated approach to managing diabesity.
Innovent Chief R&D Officer Dr. Lei Qian noted that the findings build on earlier DREAMS studies and reinforce mazdutide’s potential to address multiple metabolic abnormalities simultaneously.
Global Positioning and Outlook
Mazdutide is approved in China for chronic weight management and glycemic control in adults with T2D. Across its development program, nine Phase 3 studies have been completed or are ongoing, with five already meeting their primary endpoints.
Additional studies are evaluating mazdutide in metabolic dysfunction-associated steatohepatitis (MASH), heart failure with preserved ejection fraction (HFpEF), obstructive sleep apnea, and hypertension. A head-to-head trial against tirzepatide in moderate-to-severe obesity is also underway, which could further define mazdutide’s position among next-generation incretin-based therapies.
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About the Writer
Samiksha Vikram Jadhav (LinkedIn) is a B. Pharm graduate with a strong academic foundation in pharmaceutical sciences, pharmacology, and drug development. She specializes in pharma market research, with a focused interest in mergers and acquisitions, strategic partnerships, and global pharma and biotech deals. Her work centers on analyzing industry transactions, market positioning, and business strategies, translating complex developments into clear, accurate, and insightful scientific and commercial reporting.