Effects of once-weekly semaglutide 2.4 mg on C-reactive protein in adults with overweight or obesity (STEP 1, 2, and 3): Exploratory analyses of three randomised, double-blind, placebo-controlled, phase 3 trials

Funding and conflicts

Funding

Novo Nordisk

Industry funded

Yes

Manufacturer

Novo Nordisk, Eli Lilly, Lilly, AstraZeneca, Sanofi, Boehringer Ingelheim, Amgen, Pfizer

Sponsor role

manufacturer funded the study (sponsor role in design/analysis not stated in abstract)

Author conflicts

Dr Bhatta is an employee of Novo Nordisk A/S. Professor Davies reported receiving research funding from AstraZeneca, Boehringer Ingelheim, Janssen, 10.13039/501100004191Novo Nordisk, and Sanofi-Aventis; has acted as consultant, advisory board member, and speaker for Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi-Aventis; advisory board member and speaker for AstraZeneca; advisory board member for Gilead Sciences Ltd, Janssen, and Lexicon; and speaker for Napp Pharmaceuticals and Takeda Pharmaceuticals International Inc. She is co-funded by the NIHR Leicester Biomedical Research Centre. Dr. Deanfield reports personal fees from Amgen, Boehringer Ingelheim, Merck, Pfizer, Aegerion, Novartis, Sanofi, Takeda, Novo Nordisk, Bayer, grants from BHF, MRC(UK), NIHR, Public Health England, MSD, Pfizer, Cancer Research UK, Alzheimer’s Research UK, other from Novo Nordisk, outside the submitted work. Dr. Garvey reports grants from 10.13039/501100004191Novo Nordisk, during the conduct of the study; grants from Novo Nordisk, grants from Eli Lilly, grants from Epitomee, grants from Pfizer, personal fees from Boehringer Ingelheim, personal fees from Novo Nordisk, personal fees from Fractyl Health, personal fees from Alnylam Pharmaceuticals, personal fees from Merck, personal fees from Eli Lilly, outside the submitted work. Camilla Jensen is an employee of Novo Nordisk A/S. Dr Kandler is an employee of Novo Nordisk A/S. Dr. Kosiborod reports grants, personal fees and other from AstraZen

Independent replication

unknown

Notes

Authors declare relationships with the drug's manufacturer: Novo Nordisk

Funding is shown on every study and never used to score it.

The source, as retrieved

Abstract

[BACKGROUND] Inflammation is a key driver of atherosclerotic cardiovascular disease. C-reactive protein (CRP), an established biomarker of inflammation, is commonly elevated in people with overweight/obesity. [METHODS] STEP 1, 2, and 3 were 68-week, placebo-controlled trials of semaglutide for weight management in participants with overweight/obesity, with (STEP 2) or without (STEP 1 and 3) type 2 diabetes. Change in serum CRP from baseline to week 68 was assessed as a prespecified secondary endpoint for semaglutide 2.4 mg versus placebo (STEP 1, 2, and 3) and versus semaglutide 1.0 mg (STEP 2). Post hoc assessments included change in CRP by baseline characteristics (bodyweight, body mass index [BMI], glycaemic status, CRP concentration); change in CRP-defined cardiovascular risk category (<1 [low], 1-3 [intermediate], and >3 mg/L [high]); and correlation between change in CRP and change in bodyweight, waist circumference, fasting serum insulin (STEP 1 and 3), fasting plasma glucose, and homeostatic model assessment of insulin resistance (HOMA-IR). [FINDINGS] The trials took place from June through November 2018 (STEP 1 and 2) and from August 2018 to April 2020 (STEP 3). In all trials, semaglutide 2.4 mg reduced CRP at week 68 versus placebo (estimated treatment difference [ETD; 95% CI] -44% [-49 to -39] in STEP 1, -39% [-46 to -30] in STEP 2, and -48% [-55 to -39] in STEP 3; all p < 0.05). In STEP 2, CRP reductions were greater with semaglutide 2.4 mg (-49%) than with 1.0 mg (-42%) but the difference did not reach statistical significance (ETD [95% CI] -12% [-23 to 1]; p = 0.06). Reductions in CRP occurred in parallel with bodyweight loss and were consistent regardless of baseline BMI/bodyweight/glycaemic status. More semaglutide-treated participants had reductions in CRP-defined cardiovascular risk versus those on placebo. Reductions in CRP were positively correlated with reductions in bodyweight, waist circumference, fasting plasma glucose, fasting serum insulin, and HOMA-IR (data not shown). [INTERPRETATION] In people with overweight/obesity, once-weekly semaglutide 2.4 mg and 1.0 mg reduced CRP concentration irrespective of baseline BMI/bodyweight/glycaemic status compared with placebo. These data suggest a potential anti-inflammatory role of semaglutide in obesity. [FUNDING] Novo Nordisk.

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