Poster Presentation Australian and New Zealand Obesity Society Annual Scientific Conference 2024

Subgroup analysis by gender and body mass index (BMI) in people living with overweight/obesity in the survodutide, a glucagon/GLP-1 receptor dual agonist, phase II trial (#203)

Elif Ekinci 1 2 3 , Carel W Le Roux 4 , Oren Steen 5 , Kathryn J Lucas 6 , Elena Startseva 7 , Anna Unseld 8 , Anita M Hennige 8 , Nishant Bakshi 7
  1. Austin Health, Heidelberg West, VIC, Australia
  2. Australian Centre for Accelerating Diabetes Innovation, University of Melbourne, Parkville, Victoria, Australia
  3. Melbourne Medical School, University of Melbourne, Melbourne, Victoria, Australia
  4. St. Vincent’s University Hospital and University College Dublin School of Medicine, Dublin, Ireland
  5. LMC Diabetes & Endocrinology, Toronto, ON, Canada
  6. Diabetes& Endocrinology Consultants PC, Morehead City, NC, USA
  7. Boehringer Ingelheim International GmbH, Ingelheim am Rhein, Germany
  8. Boehringer Ingelheim PharmaGmbH & Co. KG, Biberach an der Riss, Germany

Aim: To explore the effect of gender and BMI on weight loss and adverse events (AEs) with survodutide in people living with overweight/obesity.

Methods: In this 46-week Phase II trial (NCT04667377), adults with BMI ≥27kg/m2 without diabetes were randomised 1:1:1:1:1 to weekly subcutaneous survodutide (0.6, 2.4, 3.6, 4.8mg) or placebo. Primary endpoint was percentage change in bodyweight from baseline to Week 46.

Results: Of 384 participants, 68.2% were female. At baseline, 9.9%, 30.5%, 31.8%, and 27.9% had BMI <30, 30-<35, 35-<40, and ≥40kg/m2, respectively. At Week 46, mean percentage change in bodyweight from baseline with survodutide 4.8mg/placebo was -11.9%/-3.3% in males and -17.0%/-3.2% in females, and -19.1%/-1.7%, -15.8%/-3.1%, -15.4%/-5.8%, and -13.4%/-0.8% across baseline BMI categories. Mean absolute bodyweight loss from baseline with survodutide 4.8mg/placebo was -15.9/-4.2kg in males and -22.0/-3.0kg in females. Absolute bodyweight reductions with survodutide 4.8mg/placebo were similar across BMI subgroups: -21.3/1.4kg, -16.2/-3.3kg, -22.2/-7.5kg, and -19.9/-1.6kg. Mean absolute change in waist circumference from baseline with survodutide 4.8mg/placebo was -12.8/-1.7cm in males and -17.9/-4.9cm in females, and -8.4/-2.6cm, -14.3/-6.4cm, -17.5/-5.0cm, and -17.2/3.3cm across baseline BMI categories. A higher proportion of participants lost ≥15% of baseline bodyweight with survodutide 4.8mg compared with placebo: males 31.8%/9.5%, females 66.7%/3.0%, and 75.0%/14.3%, 57.9%/4.5%, 52.0%/6.7%, and 50.0%/0.0% across baseline BMI categories, respectively. All survodutide doses (pooled) were tolerated across gender and baseline BMI subgroups. In males vs females, rates of any AE (87.9%/92.4%), serious AEs (4.0%/4.3%), and discontinuations due to AEs (25.3%/24.3%) were comparable. Gastrointestinal AEs with all survodutide doses were experienced by fewer males than females (65.7%/79.5%); mild/moderate nausea was the most frequently reported gastrointestinal AE.

Conclusion: After 46 weeks of survodutide treatment, females appeared to lose more bodyweight and waist circumference than males. Participants with lower vs higher baseline BMI generally lost more proportional bodyweight, with an opposite trend for waist circumference.