Semaglutide reveals vital weight reduction and well being advantages in four-year weight problems examine


In a current examine revealed within the journal Nature Medication, a global crew of researchers evaluated the consequences of semaglutide on weight and anthropometric outcomes, in addition to security and tolerability, in adults with weight problems however with out diabetes, throughout completely different baseline physique mass index (BMI) classes.

Study: Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial. Image Credit: Douglas Cliff / ShutterstockExamine: Lengthy-term weight reduction results of semaglutide in weight problems with out diabetes within the SELECT trial. Picture Credit score: Douglas Cliff / Shutterstock

Background 

The worldwide prevalence of weight problems (BMI ≥30 kg m−2) has almost tripled since 1975. Whereas BMI correlates with physique fats on a inhabitants degree, it could not precisely replicate fats quantity or distribution in people. Extra physique fats, significantly visceral and ectopic fats, drives cardiovascular (CV) illness (CVD) and contributes to power illnesses like diabetes and most cancers. Weight reduction can cut back these results, with modest loss bettering CV threat components and high quality of life. Attaining vital weight reduction with way of life modifications alone is difficult, however medicines like semaglutide have proven promise. Additional analysis is required to grasp the long-term impacts, optimum dosing, and potential uncomfortable side effects of semaglutide in various populations with various well being profiles.

Concerning the examine 

The current examine complies with moral laws and analyzes the Semaglutide Results on Coronary heart Illness and Stroke in Sufferers with Chubby or Weight problems (SELECT) trial, a randomized, double-blind, placebo-controlled examine. SELECT evaluated once-weekly subcutaneous semaglutide 2.4 mg versus placebo to scale back main opposed cardiac occasions in people with established CVD and chubby or weight problems with out diabetes. Accredited by regulatory and moral authorities, the trial included sufferers aged 45 years or older with a BMI of 27 kg/m−2 or increased and established CVD. All members offered knowledgeable consent.

Designed by Novo Nordisk and an educational Steering Committee, the trial concerned random project to semaglutide or placebo. The beginning dose was 0.24 mg weekly, growing each 4 weeks to a goal of two.4 mg. Dose changes have been allowed primarily based on tolerability. Investigators adopted pointers for medical remedy and way of life counseling to handle CVD, although counseling was not targeted on weight reduction.

Intercourse and race have been self-reported, and physique measurements adopted particular protocols. Endpoints included modifications in physique weight, waist circumference (WC), waist-to-height ratio (WHtR), and the proportion reaching vital weight reduction.

97.1% of the semaglutide group and 96.8% of the placebo group accomplished the trial, with 30.6% and 27.0% discontinuing remedy, respectively. Statistical analyses, primarily based on the intention-to-treat precept, used covariance fashions and a number of imputation for lacking information, with analyses carried out utilizing SAS software program.

Examine outcomes 

The examine enrolled 17,604 sufferers, 72.3% male, from 41 international locations between October 2018 and March 2021, with a imply age of 61.6 years and a BMI of 33.3 kg/m−2. The baseline traits of the inhabitants have been beforehand reported. Notably, a better proportion of Asian people was discovered within the decrease BMI classes, and the proportion of ladies elevated because the BMI class elevated. Decrease BMI classes have been related to a better ratio of sufferers with normoglycemia and decrease glycated hemoglobin ranges. Though the proportions of sufferers with excessive ldl cholesterol and smoking historical past have been related throughout BMI classes, the proportion of sufferers with high-sensitivity C-reactive protein ranges elevated with increased BMI classes.

The common proportion weight-loss trajectories with semaglutide and placebo over 4 years confirmed that weight reduction continued to week 65 and was sustained via week 208. At week 208, the semaglutide group had a imply weight lack of 10.2%, in comparison with 1.5% within the placebo group. A primary on-treatment evaluation indicated a imply weight lack of 11.7% within the semaglutide group in comparison with 1.5% within the placebo group at week 208. At week 104, weight lack of ≥5%, ≥10%, ≥15%, ≥20%, and ≥25% was achieved by 67.8%, 44.2%, 22.9%, 11.0%, and 4.9% of these handled with semaglutide, respectively, in comparison with 21.3%, 6.9%, 1.7%, 0.6%, and 0.1% for these receiving placebo.

The change in WC mirrored the change in physique weight, with a mean discount of seven.7 cm within the semaglutide group versus 1.3 cm within the placebo group at week 208. Throughout the SELECT inhabitants with a baseline BMI <35 kg/m−2, 15.0% of the semaglutide group and 14.3% of the placebo group have been under sex- and race-specific WC cutoff factors. By week 104, 41.2% of the semaglutide group fell under these cutoff factors in comparison with 18.0% of the placebo group. At baseline, the imply WHtR was 0.66, which decreased by 6.9% within the semaglutide group in comparison with 1.0% within the placebo group by week 208.

At week 104, 52.4% of sufferers handled with semaglutide improved of their BMI class in comparison with 15.7% of these receiving placebo. The proportion of overweight sufferers (BMI ≥30 kg/m−2) fell from 71.0% to 43.3% within the semaglutide group versus 71.9% to 67.9% within the placebo group. Security and tolerability have been additionally assessed, with semaglutide related to decrease charges of great opposed occasions (SAEs) throughout all BMI classes. Charges of SAEs per 100 years of remark have been decrease within the semaglutide group in comparison with the placebo group, with no vital distinction in hepatobiliary or gastrointestinal SAEs between the 2 teams.

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