Two studies presented at this year's European Congress on Obesity in Venice, Italy, have reported that tirzepatide consistently reduces body weight and waist circumference regardless of the length of time the person has been living with overweight or obesity, and also reduces body weight regardless of a person’s body mass index (BMI) before treatment.
The first study, presented by Dr Giovanna Muscogiuri, University of Naples Federico II, Naples, Italy, looked at the outcomes from the SURMOUNT phase 3 trials that evaluated tirzepatide versus placebo in people with obesity or overweight with at least 1 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 a 36-week open-label tirzepatide lead-in (SURMOUNT-4, 52 weeks from randomisation).
In this subgroup analysis, participants in each study were grouped based on overweight/obesity disease duration at baseline (ten years or less, between ten and 20 years, and above 20 years, determined by patient report). Percentage body weight change, the proportions achieving weight loss targets of 5, 10, 15, 20 and 25%, and the change in waist circumference were analysed.
Participants randomised to tirzepatide achieved greater weight reductions compared to placebo at study endpoint regardless of the duration of disease. This was consistent across the different SURMOUNT studies, and the magnitude of reduction was generally similar across the disease duration categories.
Generally, more tirzepatide-treated participants achieved the weight reduction targets of 5, 10, 15, 20 and 25% compared with placebo-treated participants, regardless of disease duration. Tirzepatide reduced waist circumference to a greater extent than placebo for each disease duration category in SURMOUNT-1 to -4. These reductions were consistent across disease duration subgroups.
For example, in the SURMOUNT-1 trial, for patients given 10mg dose of tirzepatide, those with disease duration under ten years lost 21% of their weight after 72 weeks, compared to 20% body weight loss for those with 10-20 years disease duration and 23% for those with over 20 years disease duration.
In the SURMOUNT-2 trial (where all participants were also living with type 2 diabetes), for patients given the 15mg dose of tirzepatide, those with disease duration under ten years lost 13% of their body weight, compared with 16% in those with disease duration of 10–20 years and 17% body weight loss for those living with overweight or obesity for over 20 years. Waist circumference reductions followed similar trends.
"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,” Muscogiuri concluded. “These results are consistent with the overall findings from each study in the SURMOUNT programme."
BMI
The second study, presented by Professor Carel Le Roux, University College Dublin, Ireland, examined the impact of baseline BMI category on weight reduction in these trials. The phase 3 SURMOUNT trials examined the efficacy and safety of tirzepatide versus placebo in 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 randomisation).
In this post-hoc subgroup analysis, 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). The authors examined the percent change in body weight from randomization to week 72 (SURMOUNT-1, -2, and -3) or week 52 (SURMOUNT-4), as well as the proportions of participants achieving the weight reduction targets of 5, 10, and 15%. The analyses included all randomized participants who received 1 or more doses of the study drug (tirzepatide or placebo), excluding data after premature discontinuation of study drug.
The analysis showed that across SURMOUNT 1-4, tirzepatide treatment resulted in significant body weight reductions relative to placebo, irrespective of the BMI subgroup. In addition, more participants randomised to tirzepatide than placebo achieved the body weight reduction targets of 5, 10, and 15%. Across the BMI subgroups, up to 100% of tirzepatide-treated participants achieved weight reduction of 5% or more vs. 30% with placebo in SURMOUNT-1, up to 93% vs. 43% in SURMOUNT-2, and up to 97% vs. 15% in SURMOUNT-3.
The respective proportions achieving body weight reduction of at least 10% were up to 93% vs. 16% in SURMOUNT-1, up to 76% vs. 14% in SURMOUNT-2, and up to 92% vs. 8% in SURMOUNT-3.
Furthermore, up to 85% of participants achieved weight reduction of at least 15% with tirzepatide vs. 7% with placebo in SURMOUNT-1, up to 60% vs. 3% 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 reduction was 21%. After this lead-in period, further weight reductions of ≥5, ≥10, and ≥15% were achieved by up to 70%, 39%, and 22%, respectively, of participants treated with tirzepatide vs. 2%, 2%, and 0% with placebo.
“Regardless of baseline BMI, tirzepatide consistently reduced body weight versus placebo in people with obesity across the SURMOUNT 1-4 trials. Further analyses are needed to explore and understand why patients with type 2 diabetes have less weight loss in these trials than those without type 2 diabetes. 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)," the study concluded.
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