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. 2024 Feb 10;23(1):63.
doi: 10.1186/s12933-024-02147-9.

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

Stephen J Nicholls  1 , Santiago Tofé  2 , Carel W le Roux  3   4 , David A D'Alessio  5 , Russell J Wiese  6 , Imre Pavo  7 , Katelyn Brown  6 , Govinda J Weerakkody  6 , Meltem Zeytinoglu  6 , Irene C Romera  8
Affiliations

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

Stephen J Nicholls et al. Cardiovasc Diabetol. .

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.

Keywords: Incretin; Metabolic syndrome; Tirzepatide; Type 2 diabetes.

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Conflict of interest statement

SJN has received research support from AstraZeneca, New Amsterdam Pharma, Amgen, Anthera, Eli Lilly and Company, Esperion, Novartis, Cerenis, The Medicines Company, Resverlogix, InfraReDx, Roche, Sanofi-Regeneron and LipoScience and is a consultant for AstraZeneca, Amarin, Akcea, Eli Lilly and Company, Anthera, Omthera, Merck, Takeda, Resverlogix, Sanofi-Regeneron, CSL Behring, Esperion, Boehringer Ingelheim and Vaxxinity. ST has served on advisory boards and received consulting fees from Boehringer Ingelheim, Eli Lilly and Company, Johnson and Johnson, Novo Nordisk, and Sanofi. CWlR serves on advisory boards of Novo Nordisk A/S, Herbalife, GI Dynamics, Eli Lilly and Company, Johnson & Johnson, Glia, and Boehringer Ingelheim and was gifted stockholdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. DAD receive research support from Eli Lilly and Company and participates on the Diabetes Advisory Board for Eli Lilly and Company and the steering committee for the tirzepatide CVOT. RJW, IP, KB, GJW, MZ and ICR are employees and shareholders of Eli Lilly and Company.

Figures

Fig. 1
Fig. 1
Prevalence of patients meeting the criteria for metabolic syndrome in the SURPASS clinical trial program. Data are proportion of patients with at least 3 diagnostic criteria for metabolic syndrome at the primary endpoint of 40/52 weeks. Pooled tirzepatide vs comparator was statistically significant in each trial. MET: metformin; SGLT2i: sodium-glucose co-transporter 2 inhibitor; SU: sulfonylurea
Fig. 2
Fig. 2
Prevalence of patients meeting the criteria for metabolic syndrome in tirzepatide-treated patients by weight loss category (< 5%, > 5% to ≤ 10%, > 10% to ≤ 15%, > 15% to ≤ 20%, > 20%). Data are proportion of tirzepatide-treated patients with at least 3 diagnostic criteria for metabolic syndrome at the primary endpoint of 40/52 weeks by weight loss category (< 5%, > 5% to ≤ 10%, > 10% to ≤ 15%, > 15% to ≤ 20%, > 20%). MET: metformin; SGLT2i: sodium-glucose co-transporter 2 inhibitor; SU: sulfonylurea
Fig. 3
Fig. 3
Prevalence of patients meeting the criteria for metabolic syndrome in tirzepatide-treated patients by weight loss category (< 15% or ≥ 15%). Data are proportion of tirzepatide-treated patients with at least 3 diagnostic criteria for metabolic syndrome at the primary endpoint of 40/52 weeks by weight loss category (< 15% or ≥ 15%). MET: metformin; SGLT2i: sodium-glucose co-transporter 2 inhibitor; SU: sulfonylurea
Fig. 4
Fig. 4
Prevalence of patients meeting the criteria for metabolic syndrome by SGLT2i status (yes, no). Data are proportion of tirzepatide-treated patients with at least 3 diagnostic criteria for metabolic syndrome at the primary endpoint of 40/52 weeks by SGLT2i status (yes, no). MET: metformin; SGLT2i: sodium-glucose co-transporter 2 inhibitor; SU: sulfonylurea
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