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12-01-2022 | Semaglutide | News

High-dose semaglutide reduces obesity-linked inflammatory marker

Author: Eleanor McDermid

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medwireNews: Levels of the inflammatory marker C-reactive protein (CRP) decrease in people with or without type 2 diabetes taking weekly semaglutide 2.4 mg, shows analysis of three STEP trials.

STEP 1 and 3 tested the 2.4 mg dose in people who had obesity but not type 2 diabetes while STEP 2 also included the 1.0 mg dose and was conducted in people who had both obesity and type 2 diabetes.

“CRP is elevated in obesity and is associated with the development of cardiovascular disease,” note Subodh Verma (University of Toronto, Ontario, Canada) and co-researchers in eClinicalMedicine.

Relative to placebo treatment, semaglutide 2.4 mg treatment resulted in a significant reduction in CRP levels, by an average of 44% in STEP 1 and 48% in STEP 3, and by 39% in STEP 2.

In STEP 2 there was also some evidence for a dose-response effect, with CRP decreasing by 12% more, on average, with the 2.4 than 1.0 mg dose, although this did not attain statistical significance (p=0.06).

“In our analysis of STEP 2, reductions in CRP were most pronounced up to week 20 but continued to fall after that time point,” say the researchers.

The effect of semaglutide on CRP level did not differ according to baseline bodyweight or BMI, or according to whether participants had normoglycemia, prediabetes, or type 2 diabetes. It was also consistent across subgroups of baseline CRP level.

The study authors stress that their analysis cannot separate the indirect effects of semaglutide on CRP (eg, via weight reduction) from any direct effects, although they note that evidence for a direct effect “is growing and may, in part, be attributed to changes in vascular regenerative cell production.”

The changes in CRP in all trial participants, irrespective of treatment, correlated most strongly with the change in their bodyweight, but also with changes in fasting plasma glucose, fasting serum insulin, and insulin resistance.

Verma and team note that besides being a marker of cardiovascular risk, elevated CRP also predicts the development of type 2 diabetes and the metabolic syndrome.

They say that the findings in STEP 1 and 3, in people without diabetes, therefore support “the notion that reducing inflammatory processes, as measured by CRP, in addition to lowering insulin levels and improving insulin sensitivity, could contribute to protective effects against development of type 2 diabetes and progression of cardiometabolic disease.”

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2022 Springer Healthcare Ltd, part of the Springer Nature Group

eClinicalMedicine 2022; doi:10.1016/j.eclinm.2022.101737

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