Diabetes drug helps weight loss regardless of how overweight or obese a patient is, and for how long

Funder: See media release for full list of disclosures.

Media release

From: European Congress on Obesity

Tirzepatide reduces bodyweight regardless of pre-treatment BMI or duration of disease – European Congress on Obesity

Embargo for both parts: 2301H UK time Wednesday 13 March

·       New analysis shows tirzepatide consistently reduces bodyweight regardless of body mass index (BMI) before treatment

·       Tirzepatide reduces body weight and waist circumference in people living with overweight or obesity regardless of duration of their condition

New analysis shows tirzepatide consistently reduces bodyweight regardless of body mass index (BMI) before treatment

Embargo – 2301H UK time Wednesday 13 March

*Note – this is an early press release from the European Congress on Obesity in Venice, Italy 12-15 May. Please credit the congress when using this research*

Tirzepatide, a medication authorised to treat obesity and/or type 2 diabetes, consistently reduces bodyweight regardless of the patient’s body mass index (BMI before treatment), from the range of overweight to class III obesity. The study, to be presented at this year’s European Congress on Obesity (Venice, Italy, 12-15 May) is by Prof Carel Le Roux, University College Dublin, Ireland, and Dr Louis J Aronne, Comprehensive Weight Control Center, Division of Endocrinology, Diabetes & Metabolism, Weill Cornell Medicine, New York, USA, and colleagues from Eli Lilly and Company, the manufacturer of tirzepatide.

Tirzepatide (Mounjaro®) was approved by the US Food and Drug administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound®) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity.  Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro® label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.

This new analysis examined the impact of baseline body mass index (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 randomisation) 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 randomisation 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 randomised 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 (see figure full abstract). 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).” said Dr. Aronne.

Prof Le Roux added: “Tirzepatide is one of the most effective treatments we have for the disease of obesity, and not only can we control the disease but we are also able to disrupt the complications of obesity such as type 2 diabetes.”

Conflicts of interest:

Prof Le Roux reports grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He serves on advisory boards of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Roche, AstraZeneca, Janssen, Bristol-Myers Squibb, Glia, and Boehringer Ingelheim. ClR is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He is the chief medical officer and director of the Medical Device Division of Keyron since January 2011. Both of these are unremunerated positions. ClR was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. The product has only been tested in rodents and none of Keyron’s products are currently licensed. They do not have any contracts with other companies to put their products into clinical practice. No patients have been included in any of Keyron’s studies and they are not listed on the stock market. ClR was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September, 2021. He continues to provide scientific advice to Keyron for no remuneration.

Dr Aronne is a consultant to Eli-Lilly and investigator on Surmount -1 and other trials of tirzepatide.  He also has other industry relationships to manufacturers of diabetes and obesity medications (more listed in full abstract)

All other authors are employees of Eli Lilly and Company, the manufacturer of tirzepatide

This press release is based on abstract 14 to be presented at this year’s European Congress on Obesity (ECO 2024) in Venice, Italy. The material has been peer reviewed by the congress selection committee. There is no full paper at this stage, and it has not yet been submitted to a medical journal.

Tirzepatide reduces body weight and waist circumference in people living with overweight or obesity regardless of duration of their condition

Embargo – 2301H UK time Wednesday 13 March

*Note – this is an early press release from the European Congress on Obesity in Venice, Italy 12-15 May. Please credit the congress when using this research*

New research to be presented at this year’s European Congress on Obesity (Venice, Italy, May 12-15) shows that the obesity medication tirzepatide consistently reduces bodyweight and waist circumference regardless of the length of time the person has been living with overweight or obesity. The study is by Dr Giovanna Muscogiuri, University of Naples Federico II, Naples, Italy, and colleagues.

Tirzepatide (Mounjaro®) was approved by the US Food and Drug administration (FDA) and the European Medicines Agency (EMA) for the treatment of type 2 diabetes in 2022. In November 2023, the FDA approved tirzepatide (Zepbound®) for chronic weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 with at least one weight-related comorbidity.  Also in November 2023, the EMA Committee for Medicinal Products for Human Use offered a positive opinion on extension of the Mounjaro® label to include weight management in adults with BMI ≥ 30 kg/m2 or BMI ≥ 27 kg/m2 and at least one weight-related comorbid condition.

The SURMOUNT phase 3 trials 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 randomisation) 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 (10 years or less, between 10 and 20 years, and above 20 years, determined by patient report). Percentage bodyweight 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 (see figure in full abstract). 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 (see table in full abstract). 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 10 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 10 years lost 13% of their bodyweight, compared with 16% in those with disease duration of 10-20 years and 17% bodyweight loss for those living with overweight or obesity for over 20 years.  Waist circumference reductions followed similar trends (see table full abstract).

The authors conclude: “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 programme.”

Conflicts of interest:

Dr Muscogiuri declares no conflicts of interest

Dr Pedersen’s disclosure can be found here

All other authors are employees of Eli Lilly and Company, the manufacturer of tirzepatide

This press release is based on abstract 187 to be presented at this year’s European Congress on Obesity (ECO 2024) in Venice, Italy. The material has been peer reviewed by the congress selection committee. There is no full paper at this stage. The work has not yet been submitted to a medical journal.

SOURCE

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