The tolerability to benefit ratio based on maximum weight loss observed was not considered favorable at the doses studied and the study was terminated early

This was a multi-center, randomized, placebo-controlled, participant-and-investigator-blinded, sponsor open-label study in obese participants with or without Type 2 Diabetes Mellitus.

The study comprised a screening/baseline period of up to 35 days (5 weeks), a 14-week treatment period in which participants were administered MBL949 or placebo at 8 biweekly intervals starting on Day 1 and a 10-week follow-up period.

Participants were to be enrolled to:

• MBL949 Arm 1, MBL949 Arm 2 and placebo in a 1:1:1 ratio
• MBL949 Arm 3, MBL949 Arm 4 and placebo in a 1:1:1 ratio
• If MBL949 Arm 1 was tolerated, MBL949 Arm 5 was enrolled with a 2:1 ratio (MBL:placebo) within each stratum.

Inclusion Criteria:

• Body mass index: ≥ 32 kg/m2, weight ≥ 77 kg, stable body weight i.e., less than 1.5 kg self-reported change within 90 days

• Diagnosed T2DM as documented by medical history and confirmed by Investigator and with diagnosed duration < 10 yrs, HbA1c ≤ 9%, and fasting C-peptide ≥ 0.2 ng/ml

• If treated for T2DM, treatment must be limited to diet and exercise and treatment with one of the following anti-diabetic agents (stable for 90 days prior to randomization):

  • Metformin
  • SGLT2i inhibitors (if prescribed as the first line, ie. single agent)
  • DDP4 inhibitors
  • Acarbose

Exclusion Criteria:

• Vitals at screening:

  • systolic blood pressure less than 95 mm Hg or greater than 155 mm Hg
  • diastolic blood pressure less than 60 mg Hg or greater than 95 mm Hg
  • pulse rate less than 56 or greater than 110 bpm

• History of bariatric surgery, Roux-en-Y Gastric Bypass, Sleeve Gastrectomy, gastric banding, and any other intrabdominal procedures designed for weight loss at screening

• History of myocardial infarction with 2 years of screening

• Diet attempts within 90 days before screening

• Participation in organized weight reduction program within 6 months of screening

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Adverse events were reported from first dose of study treatment until end of study treatment plus 10 weeks post treatment, up to a maximum duration of 169 days.

Each treatment arm contains a different dosing scheme and adverse event data is provided for the full sequence.