Highlight
At the 2025 American Diabetes Association (ADA) Scientific Sessions, several pivotal studies presented promising advances in obesity and diabetes management. Key highlights include the introduction of CagriSema, a dual agonist combining semaglutide and cagrilintide, which demonstrated superior weight loss compared to monotherapy. The BELIEVE trial revealed a novel combination of semaglutide with bimagrumab that promotes fat mass loss while preserving lean muscle. The SOUL trial confirmed cardiovascular benefits of oral semaglutide in high-risk type 2 diabetes patients. Additionally, the PATHWEIGH care model optimized obesity management in primary care. In pediatric type 1 diabetes, inhaled insulin showed noninferior glycemic control with less weight gain and higher patient satisfaction. Finally, a randomized trial demonstrated that switching from diet beverages to water significantly enhanced weight loss and diabetes remission in women with type 2 diabetes undergoing weight management.
Obesity and type 2 diabetes mellitus (T2DM) remain major global health challenges, contributing to increased cardiovascular and renal morbidity and mortality. Weight management is central to improving glycemic control and reducing complications. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have revolutionized treatment by promoting weight loss and cardiovascular benefits. However, adverse effects such as muscle loss and patient reluctance toward injectable therapies limit their uptake. Moreover, lifestyle interventions including dietary modifications remain foundational but challenging to sustain. In pediatric type 1 diabetes (T1DM), optimizing insulin delivery to improve adherence and minimize side effects like weight gain is critical. The integration of novel pharmacologic agents with practical care models and lifestyle strategies is imperative to address these unmet needs.
The ADA 2025 sessions featured multiple clinical trials:
– REDEFINE 1 and 2: Phase 3 randomized, placebo-controlled trials testing CagriSema (semaglutide plus cagrilintide) versus individual components and placebo in adults with obesity, with and without T2DM.
– BELIEVE trial: Phase 2b trial evaluating semaglutide combined with bimagrumab, a monoclonal antibody targeting activin type II receptors, focusing on weight loss composition.
– SOUL trial: Cardiovascular outcomes trial assessing oral semaglutide (Rybelsus) in T2DM patients at high cardiovascular risk, comparing major adverse cardiovascular events (MACE).
– PATHWEIGH: Pragmatic trial implementing an obesity care delivery model in primary care, comparing weight-prioritized visits and previsit questionnaires against usual care.
– INHALE-1 trial: Pediatric trial comparing inhaled rapid-acting insulin versus subcutaneous insulin in children aged 4–17 years with T1DM.
– Diet drinks versus water trial: Randomized study involving women with T2DM in a weight management program, comparing outcomes after switching from diet beverages to water.
Key Findings
CagriSema Dual Agonist (REDEFINE 1 and 2)
The combination of semaglutide and cagrilintide led to approximately 20% mean weight loss, outperforming semaglutide alone (15%), cagrilintide alone (12%), and placebo (3%). Notably, over 70% of participants achieved these results at submaximal doses, suggesting a favorable side effect profile and flexible dosing.
BELIEVE Trial: Muscle-Preserving Weight Loss
Combining semaglutide with bimagrumab resulted in weight loss predominantly from fat mass (93%), sparing lean muscle mass. This contrasts with typical weight-loss interventions where muscle loss is common, highlighting the potential of bimagrumab to preserve or increase lean mass during therapy.
SOUL Trial: Cardiovascular Outcomes with Oral Semaglutide
Oral semaglutide reduced the incidence of major adverse cardiovascular events by 14% compared to placebo in high-risk T2DM patients. Unlike the injectable formulation, oral semaglutide did not demonstrate kidney benefits in this trial. The oral route offers advantages in patient acceptance and pharmacy handling.
PATHWEIGH Care Model
Implementation of a structured obesity management pathway in primary care prevented weight gain in over 250,000 patients. The model utilized electronic medical record optimizations, previsit questionnaires, and weight-focused visits without disrupting workflow. Improved coding practices generated $15 million in additional revenue over four years, demonstrating both clinical and economic benefits.
INHALE-1 Trial: Inhaled Insulin in Pediatric T1DM
Inhaled insulin was noninferior to rapid-acting subcutaneous insulin after exclusion of an outlier. It was associated with less weight gain and higher patient and parent satisfaction, indicating a promising alternative for insulin delivery in children aged 4 to 17 years.
Water Versus Diet Beverages Trial
Women with T2DM who switched from diet drinks to water achieved an additional 2 kg weight loss and had a 90% diabetes remission rate compared to 45% in those continuing diet drinks, despite both groups participating in weight management programs. This finding underscores the metabolic benefit of replacing even non-sugar sweetened beverages with water.
Expert Commentary
Dr. Raveendhara Bannuru, ADA’s Vice President of Medical Affairs, highlighted the clinical promise of these advances. He emphasized the flexible dosing and reduced side effects of CagriSema, the importance of muscle preservation with bimagrumab, and the practical benefits of oral semaglutide. He noted that PATHWEIGH’s integration into primary care workflows facilitates sustainable obesity management with added financial incentives. The inhaled insulin option was praised for improving patient and caregiver satisfaction, particularly in children. Finally, he underscored the significance of the water versus diet drink trial as a simple, evidence-based behavior modification with profound clinical effects.
While the REDEFINE trials demonstrated impressive weight loss, longer-term safety and durability data are awaited. The BELIEVE trial is phase 2b with a smaller sample size, necessitating confirmatory phase 3 studies. The lack of kidney benefit with oral semaglutide in SOUL contrasts with injectable formulations, warranting further investigation. PATHWEIGH’s success in a single health system may limit generalizability. Inhaled insulin’s long-term pulmonary safety remains to be fully elucidated. The diet beverage trial, although randomized, focused on a specific population of women with T2DM, and results may not extrapolate broadly.
Conclusion
The ADA 2025 Scientific Sessions showcased important advances in pharmacologic and behavioral approaches to obesity and diabetes management. The development of dual agonist therapies like CagriSema and muscle-sparing combinations such as semaglutide plus bimagrumab promise enhanced efficacy and safety profiles. Oral semaglutide’s cardiovascular benefits expand treatment options for T2DM, while pragmatic care models like PATHWEIGH enable scalable obesity management in primary care. Innovations in insulin delivery, including inhaled formulations, address pediatric treatment challenges. Lastly, lifestyle interventions, exemplified by substituting water for diet beverages, remain a cornerstone with measurable metabolic benefits. Together, these findings support a multidisciplinary, patient-centered approach to combat the growing burden of obesity and diabetes.
References
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6. Heinemann L, Pieber TR, Riddle MC, et al. Inhaled Insulin in Children with Type 1 Diabetes: INHALE-1 Trial Results. Diabetes Care. 2025;48(3):e34-e40.
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