The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes

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Wilson , J M , Nikooienejad , A , Robins , D A , Roell , W C , Riesmeyer , J S , Haupt , A , Duffin , K L , Taskinen , M-R & Ruotolo , G 2020 , ' The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes ' , Diabetes, obesity and metabolism , vol. 22 , no. 12 , pp. 2451-2459 . https://doi.org/10.1111/dom.14174

Title: The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes
Author: Wilson, Jonathan M.; Nikooienejad, Amir; Robins, Deborah A.; Roell, William C.; Riesmeyer, Jeffrey S.; Haupt, Axel; Duffin, Kevin L.; Taskinen, Marja-Riitta; Ruotolo, Giacomo
Other contributor: University of Helsinki, HUS Heart and Lung Center




Date: 2020-12
Language: eng
Number of pages: 9
Belongs to series: Diabetes, obesity and metabolism
ISSN: 1462-8902
DOI: https://doi.org/10.1111/dom.14174
URI: http://hdl.handle.net/10138/325991
Abstract: Aim To better understand the marked decrease in serum triglycerides observed with tirzepatide in patients with type 2 diabetes, additional lipoprotein-related biomarkers were measured post hoc in available samples from the same study. Materials and Methods Patients were randomized to receive once-weekly subcutaneous tirzepatide (1, 5, 10 or 15 mg), dulaglutide (1.5 mg) or placebo. Serum lipoprotein profile, apolipoprotein (apo) A-I, B and C-III and preheparin lipoprotein lipase (LPL) were measured at baseline and at 4, 12 and 26 weeks. Lipoprotein particle profile by nuclear magnetic resonance was assessed at baseline and 26 weeks. The lipoprotein insulin resistance (LPIR) score was calculated. Results At 26 weeks, tirzepatide dose-dependently decreased apoB and apoC-III levels, and increased serum preheparin LPL compared with placebo. Tirzepatide 10 and 15 mg decreased large triglyceride-rich lipoprotein particles (TRLP), small low-density lipoprotein particles (LDLP) and LPIR score compared with both placebo and dulaglutide. Treatment with dulaglutide also reduced apoB and apoC-III levels but had no effect on either serum LPL or large TRLP, small LDLP and LPIR score. The number of total LDLP was also decreased with tirzepatide 10 and 15 mg compared with placebo. A greater reduction in apoC-III with tirzepatide was observed in patients with high compared with normal baseline triglycerides. At 26 weeks, change in apoC-III, but not body weight, was the best predictor of changes in triglycerides with tirzepatide, explaining up to 22.9% of their variability. Conclusions Tirzepatide treatment dose-dependently decreased levels of apoC-III and apoB and the number of large TRLP and small LDLP, suggesting a net improvement in atherogenic lipoprotein profile.
Subject: incretin therapy
type 2 diabetes
TRIGLYCERIDE-RICH LIPOPROTEINS
APOLIPOPROTEIN C-III
APOC-III
POLYPEPTIDE RECEPTOR
HEPATIC LIPASE
LIPIDS
LIRAGLUTIDE
MECHANISMS
OUTCOMES
THERAPY
3121 General medicine, internal medicine and other clinical medicine
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