Semaglutide aids weight loss in adults with type 2 diabetes and reduces major adverse cardiovascular events

Weight control remains an indispensable component for the clinical management of type 2 diabetes mellitus (T2DM) in preventing cardiometabolic morbidity.1-3 People with T2DM who received weekly subcutaneous injection of semaglutide 2.4mg achieved superior and clinically meaningful reduction of body weight as compared to placebo.1 Another study showed that semaglutide can reduce the incidence of major adverse cardiovascular events (MACE) in high risk patients.4 Similar degree of weight reduction and adverse reactions were also observed in obese individuals without T2DM.2-3 The majority of adverse effects of semaglutide were mild to moderate gastrointestinal disturbance.1

Pathogenesis of T2DM involves the impairment of the incretin system.5-6 The insufficient physiological response to glucagon-like peptide 1 (GLP-1) impaired glucose-dependent insulinotropic and glucagonostatic effects, resulting in abnormal insulin/glucagon production, accelerated apoptosis of pancreatic beta-cells and overeating.6 Semaglutide is a long acting GLP-1 receptor agonist with proven activities on weight management in T2DM and, at the same time, it can sustain normoglycemia and reduce the incidence of MACE.2,4 Following the positive findings in healthy individuals, the workgroup on Semaglutide Treatment Effect in People with Obesity (STEP) program has recently completed a phase 3 trial on the efficacy and safety of semaglutide for weight control in T2DM.1-3

In the phase 3 trial, 1,595 patients diagnosed with T2DM from 12 countries across Europe, Asia, Africa, and America were recruited. They were randomized 1:1:1 into three groups: Semaglutide 2.4mg, semaglutide 1.0mg and placebo. Body weight was recorded at baseline and monitored over 68 weeks. At the end of the study, the mean bodyweight of the participants receiving semaglutide 2.4mg was reduced by 9.6% versus 3.4% in the placebo group. More than 68% of the semaglutide 2.4mg group had more than 5% bodyweight reduction by week 68 [OR=4.88; 95% CI: 3.58-6.64; p<0.001]. In the same semaglutide 2.4mg group, 25.8% had more than 15% bodyweight reduction at the end of the study (OR=7.65; 95% CI: 4.11-14.22; p<0.001).2

Semaglutide was also effective in controlling hyperglycemia and reducing risk for MACE.2,4 Compared to baseline, semaglutide 2.4mg had a greater reduction in HbA1c level when compared to placebo at week 68 (-17.5% vs. -4.1%; p<0.001).4 In addition, systolic blood pressure and systemic inflammation (C-reactive protein) were also lower in the semaglutide 2.4mg group as compared to the placebo group at the end of the study.4 Although cardiovascular outcomes were not directly investigated by the STEP working group, several independent trials have evaluated MACE composite outcome when injective semaglutide was given to T2DM.4

In the Trial to Evaluate Cardiovascular and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes (SUSTAIN 6) trial, semaglutide was associated with a lower risk for nonfatal cerebrovascular accident [Hazard ratio (HR)=0.61, 95% CI: 0.38-0.99; p=0.04] and nonfatal myocardial infarction (HR=0.74, 95% CI: 0.51-1.08; p=0.12). In other cardiovascular outcomes trials, a similar MACE benefit was observed among T2DM patients receiving semaglutide.4 To conclude, despite mild to moderate gastrointestinal disturbance, injectable semaglutide is effective for weight loss in adults with T2DM and confers additional advantage on those with high risk for cardiovascular sequelae.

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