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Tirzepatide Controls Lipids and Metabolites in Type 2 Diabetes

According to a study, treatment with tirzepatide reduces body weight and improves glycemic control in people with type 2 diabetes (T2D). Furthermore, it affects metabolites linked to T2D risk and metabolic dysregulation, indicating enhanced metabolic health.

Tirzepatide Controls Lipids and Metabolites in Type 2 Diabetes
Image: Diabetes Patient Getting Blood Sugar Test | InStyleHealth

Over the course of 26 weeks, 259 T2D patients were randomly assigned to receive weekly subcutaneous tirzepatide (1, 5, 10, 15 mg), dulaglutide (1.5 mg), or placebo. Post hoc exploratory metabolomics and lipidomics, as well as post hoc analyses, were done by the researchers. They compared changes in metabolic levels in response to tirzepatide to baseline levels, dulaglutide, and placebo using multiplicity correction.


At 26 weeks, a larger dose of tirzepatide controlled a group of metabolites and lipids linked to insulin resistance (IR), obesity, and T2D risk. Direct catabolic products glutamate, 3-hydroxyisobutyrate, branched-chain ketoacids, and indirect byproducts all decreased when compared to baseline and placebo.


Tirzepatide caused much more changes than dulaglutide, and decreases in HbA1c, homeostatic model assessment 2-IR indices, and proinsulin levels were exactly proportionate. Triglycerides and diglycerides declined in proportion to metabolite alterations in comparison to baseline, dulaglutide, and placebo, with a bias toward shorter and highly saturated species.


"When compared to the glucagon-like peptide 1 receptor agonist dulaglutide, tirzepatide significantly lowered HbA1c and body weight in [individuals] with T2D," the researchers wrote. "Enhanced glycemic management was linked to decreased circulating triglycerides and lipoprotein indicators, as well as improved beta-cell function and IR markers, results that were only partially due to weight loss."

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