Tirzepatide (Zepbound for weight loss; Mounjaro for type 2 diabetes; Eli Lilly) consistently reduced body weight regardless of pretreatment body mass index (BMI) and reduced body weight and waist circumference regardless of duration of overweight or obesity.
The analyses — firstly of the impact of baseline BMI and secondly investigating the impact of the duration of overweight/obesity — are drawn from combined findings from the SURMOUNT 1-4 studies that examined the efficacy and safety of tirzepatide vs placebo. They are scheduled to be presented at May’s European Congress on Obesity (ECO) by Carel Le Roux, MD, University College Dublin, Ireland, and Giovanna Dr. Muscogiuri, MD, endocrinologist from the University of Naples Federico II, Naples, Italy, respectively.
The first analysis of tirzepatide, a dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide 1 receptor agonist, aimed to analyze the impact of baseline BMI category on weight reduction across the series of phase 3 trials.
More participants on tirzepatide than on placebo achieved the body weight reduction targets of 5%, 10%, and 15%. “Across the SURMOUNT 1-4 trials, treatment with tirzepatide, along with a reduced-calorie diet and increased physical activity, consistently resulted in clinically significant weight reductions of 5% or more, 10% or more, or 15% or more, as compared to placebo, regardless of baseline BMI subgroup, in adults with obesity or overweight (BMI of 27 and above),” said obesity specialist, Louis J. Aronne, MD, from the Comprehensive Weight Control Center, Weill Cornell Medicine, New York City, and coauthor of the BMI-related analysis.
Dr. Muscogiuri, who is first author of the second analysis that looked at the impact of duration of adiposity, and her coauthors concluded that, “Tirzepatide consistently reduced body weight and waist circumference in people living with obesity or overweight with weight-related comorbidities regardless of the duration of disease. These results are consistent with the overall findings from each study in the SURMOUNT program.”
Weight Loss Consistent Regardless of BMI
The SURMOUNT series of trials involved people with a BMI of 30 kg/m2 and above, or 27 kg/m2 with at least one weight-related comorbidity without type 2 diabetes (SURMOUNT-1, 72 weeks), with type 2 diabetes (SURMOUNT-2, 72 weeks), and without type 2 diabetes after a 12-week intensive lifestyle intervention (SURMOUNT-3, 72 weeks from randomization) or after an 88 week intervention (SURMOUNT-4, 36-week open label tirzepatide lead-in and 52 weeks following randomization).
BMI subgroups were defined by 27-30 (overweight), 30-35 (obesity class I), 35-40 (obesity class II), and 40 kg/m2 and above (obesity class III). Percentage change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or to week 52 (SURMOUNT-4) was determined, as well as the proportions of participants achieving the weight reduction targets of 5%, 10%, and 15%. The per protocol analyses included all participants who received at least one dose of tirzepatide or placebo.
Across these BMI levels, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more compared with 30% on placebo in SURMOUNT-1, up to 93% vs 43% in SURMOUNT-2, and up to 97% vs 15%, respectively, in SURMOUNT-3.
At least 10% weight reduction was achieved by up to 93% vs 16%, respectively, in SURMOUNT-1, up to 76% vs 14% in SURMOUNT-2, and up to 92% vs 8% in SURMOUNT-3.
Weight reduction of 15% was achieved by up to 85% compared with 7% of patients on tirzepatide and placebo, respectively, in SURMOUNT-1; up to 60% vs 3%, respectively, in SURMOUNT-2; and up to 78% vs 4% in SURMOUNT-3.
In SURMOUNT-4, during the 36-week open-label tirzepatide treatment, the mean body weight % or more reduction was 21%. Following this lead-in period, further weight reductions of 5% or more, 10%, and 15% or more were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide compared with 2%, 2%, and 0% of patients on placebo.