TY - JOUR
T1 - Semaglutide improves cardiometabolic risk factors in adults with overweight or obesity
T2 - STEP 1 and 4 exploratory analyses
AU - Kosiborod, Mikhail N.
AU - Bhatta, Meena
AU - Davies, Melanie
AU - Deanfield, John E.
AU - Garvey, W. Timothy
AU - Khalid, Usman
AU - Kushner, Robert
AU - Rubino, Domenica M.
AU - Zeuthen, Niels
AU - Verma, Subodh
N1 - Funding Information:
This work was supported by Novo Nordisk A/S. The authors thank the participants, investigators, and site staff involved in the STEP 1 and 4 trials. Medical writing support was provided by Sophie Walton, MSc, CMPP, of Axis, and Sarah Stowell, PhD, a contract writer working on behalf of Axis, a division of Spirit Medical Communications Group Limited, and funded by Novo Nordisk A/S, in accordance with Good Publication Practice 3 (GPP3) guidelines ( www.ismpp.org/gpp3 ).
Publisher Copyright:
© 2022 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.
PY - 2023/2
Y1 - 2023/2
N2 - Aims: Evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight/obesity without diabetes in the STEP 1 and 4 trials. Materials and Methods: STEP 1 and 4 were phase III, 68-week, placebo-controlled trials of once-weekly semaglutide 2.4 mg combined with lifestyle intervention; STEP 4 had a 20-week semaglutide run-in and 48-week randomized withdrawal period. Participants had a body mass index ≥30 kg/m2 or ≥27 kg/m2 with one or more weight-related comorbidity, without diabetes. Pre-specified endpoints were changes in waist circumference, systolic/diastolic blood pressure (SBP/DBP), lipids, fasting plasma glucose (FPG), fasting serum insulin and antihypertensive/lipid-lowering medication use. Post-hoc assessments included non-high-density lipoprotein (HDL) cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR; STEP 1 only), atherosclerotic cardiovascular disease (ASCVD) risk (American College of Cardiology/American Heart Association algorithm; STEP 1 only) and cardiometabolic risk factors by weight loss achieved (<5%, 5% to <10%, 10% to <15%, or ≥15%) (STEP 1 only). Results: Of the 1961 participants in STEP 1 and 803 in STEP 4, most had one or more complication/comorbidity at baseline, with dyslipidaemia and hypertension most prevalent. In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA-IR were greater with semaglutide versus placebo (p ≤.001). Reductions in SBP, non-HDL cholesterol, low-density lipoprotein cholesterol and FPG were generally greater with semaglutide than placebo within weight-loss categories. Non-significant ASCVD risk reductions were observed with semaglutide versus placebo (p >.05). In STEP 4, improvements in waist circumference, SBP, FPG, fasting serum insulin and lipids during the semaglutide run-in (week 0-20) were maintained over week 20-68 with continued semaglutide, but deteriorated following the switch to placebo (p <.001 [week 20-68]). Net reductions in antihypertensive/lipid-lowering medication use occurred with semaglutide versus placebo (both trials). Conclusions: Semaglutide may improve cardiometabolic risk factors and reduce antihypertensive/lipid-lowering medication use versus placebo in adults with overweight/obesity without diabetes. These potential benefits were not maintained after treatment discontinuation. ClinicalTrials.gov numbers: STEP 1 NCT03548935, STEP 4 NCT03548987.
AB - Aims: Evaluate the effects of once-weekly subcutaneous semaglutide 2.4 mg on cardiometabolic risk factors in people with overweight/obesity without diabetes in the STEP 1 and 4 trials. Materials and Methods: STEP 1 and 4 were phase III, 68-week, placebo-controlled trials of once-weekly semaglutide 2.4 mg combined with lifestyle intervention; STEP 4 had a 20-week semaglutide run-in and 48-week randomized withdrawal period. Participants had a body mass index ≥30 kg/m2 or ≥27 kg/m2 with one or more weight-related comorbidity, without diabetes. Pre-specified endpoints were changes in waist circumference, systolic/diastolic blood pressure (SBP/DBP), lipids, fasting plasma glucose (FPG), fasting serum insulin and antihypertensive/lipid-lowering medication use. Post-hoc assessments included non-high-density lipoprotein (HDL) cholesterol, homeostatic model assessment of insulin resistance (HOMA-IR; STEP 1 only), atherosclerotic cardiovascular disease (ASCVD) risk (American College of Cardiology/American Heart Association algorithm; STEP 1 only) and cardiometabolic risk factors by weight loss achieved (<5%, 5% to <10%, 10% to <15%, or ≥15%) (STEP 1 only). Results: Of the 1961 participants in STEP 1 and 803 in STEP 4, most had one or more complication/comorbidity at baseline, with dyslipidaemia and hypertension most prevalent. In STEP 1, reductions in waist circumference, SBP, DBP, FPG, fasting serum insulin, lipids and HOMA-IR were greater with semaglutide versus placebo (p ≤.001). Reductions in SBP, non-HDL cholesterol, low-density lipoprotein cholesterol and FPG were generally greater with semaglutide than placebo within weight-loss categories. Non-significant ASCVD risk reductions were observed with semaglutide versus placebo (p >.05). In STEP 4, improvements in waist circumference, SBP, FPG, fasting serum insulin and lipids during the semaglutide run-in (week 0-20) were maintained over week 20-68 with continued semaglutide, but deteriorated following the switch to placebo (p <.001 [week 20-68]). Net reductions in antihypertensive/lipid-lowering medication use occurred with semaglutide versus placebo (both trials). Conclusions: Semaglutide may improve cardiometabolic risk factors and reduce antihypertensive/lipid-lowering medication use versus placebo in adults with overweight/obesity without diabetes. These potential benefits were not maintained after treatment discontinuation. ClinicalTrials.gov numbers: STEP 1 NCT03548935, STEP 4 NCT03548987.
KW - GLP-1 analogue
KW - cardiovascular disease
KW - obesity therapy
KW - randomized trial
KW - weight control
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U2 - 10.1111/dom.14890
DO - 10.1111/dom.14890
M3 - Article
C2 - 36200477
AN - SCOPUS:85141342505
VL - 25
SP - 468
EP - 478
JO - Diabetes, Obesity and Metabolism
JF - Diabetes, Obesity and Metabolism
SN - 1462-8902
IS - 2
ER -
