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Reduction of prevalence of patients meeting the criteria for metabolic syndrome with tirzepatide: a post hoc analysis from the SURPASS Clinical Trial Program

Nicholls, Stephen J., Tofé, Santiago, le Roux, Carel W., D’Alessio, David A., Wiese, Russell J., Pavo, Imre, Brown, Katelyn, Weerakkody, Govinda J., Zeytinoglu, Meltem, Romera, Irene C.·2024·Cardiovascular Diabetology
DOI 10.1186/s12933-024-02147-9PMC PMC10859014
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Abstract

Background: Metabolic syndrome is characterized as the co-occurrence of interrelated cardiovascular risk factors, including insulin resistance, hyperinsulinemia, abdominal obesity, dyslipidemia and hypertension. Once weekly tirzepatide is approved in the US and EU for the treatment of type 2 diabetes (T2D) and obesity. In the SURPASS clinical trial program for T2D, tirzepatide demonstrated greater improvements in glycemic control, body weight reduction and other cardiometabolic risk factors versus placebo, subcutaneous semaglutide 1 mg, insulin degludec, and insulin glargine. This post hoc analysis assessed the effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome across SURPASS 1–5. Methods: Metabolic syndrome was defined as having ≥ 3 of 5 criteria according to the US National Cholesterol Education Program: Adult Treatment Panel III. Analyses were based on on-treatment data at the primary endpoint from patients adherent to treatment (taking ≥ 75% study drug). A logistic regression model with metabolic syndrome status as the response variable, metabolic syndrome status at the baseline visit as an adjustment, and randomized treatment as fixed explanatory effect was used. The effect of tirzepatide use on the prevalence of patients meeting the criteria for metabolic syndrome by categorical weight loss, background medication and gender were assessed. Results: In SURPASS, the prevalence of patients meeting the criteria for metabolic syndrome at baseline was 67–88% across treatment groups with reductions at the primary endpoint to 38–64% with tirzepatide versus 64–82% with comparators. Reductions in the prevalence of patients meeting the criteria for metabolic syndrome was significantly greater with all tirzepatide doses versus placebo, semaglutide 1 mg, insulin glargine, and insulin degludec (p < 0.001). Individual components of metabolic syndrome were also reduced to a greater extent with tirzepatide vs comparators. Greater reductions in body weight were associated with greater reductions in the prevalence of patients meeting the criteria for metabolic syndrome and its individual components. Background SGLT2i or sulfonylurea use or gender did not impact the change in prevalence of patients meeting the criteria for metabolic syndrome. Conclusions: In this post hoc analysis, tirzepatide at all doses studied was associated with a greater reduction in the prevalence of patients meeting the criteria for metabolic syndrome compared to placebo, semaglutide 1 mg, insulin degludec, and insulin glargine. Although more evidence is needed, these data would support greater potential improvement in cardiovascular risk factor profile with tirzepatide treatment in people across the continuum of T2D.

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  • Tirzepatide is a dual agonist at the GLP-1 and glucose-dependent insulinotropic polypeptide receptors and has been demonstrated to produce incremental benefits on glycaemic control, weight loss and associated metabolic risk factors in patients with type 2 diabetes compared with selective GLP-1 receptor agonists.

    “Tirzepatide is a dual agonist at the GLP-1 and glucosedependent insulinotropic polypeptide (GIP) receptors and has been demonstrated to produce incremental benefits on glycaemic control, weight loss and associated metabolic risk factors in patients with T2D in comparison with selective GLP-1 receptor agonists.[10][11][12]”

    From Outcomes in patients with diabetes, atherosclerotic cardiovascular disease, and heart failure treated with tirzepatide or dulaglutide: SURPASS-CVOT analysis (2026) · cites this paper as [12]

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Metadata

Authors
Nicholls, S. J., Tofé, S., le Roux, C. W., D’Alessio, D. A., Wiese, R. J., Pavo, I., Brown, K., Weerakkody, G. J., Zeytinoglu, M., & Romera, I. C.
Venue
Cardiovascular Diabetology
Publisher
Springer Science and Business Media LLC
Published
2024-02-10
Volume
23
Issue
1
ISSN
1475-2840
DOI
10.1186/s12933-024-02147-9
PMC
PMC10859014
Cited by
11
References
17
Language
en
Licence
Funders
Eli Lilly and Cmpany

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