Obesity — can you lose weight without starving yourself?

Aim of the study: The weight loss benefit of semaglutide in patients with diabetes is well-documented, but its clinical utility in treating obesity among patients without diabetes is less described. We therefore assessed the efficacy and safety of subcutaneous semaglutide as treatment for obesity in patients without diabetes.

Results: The study included 4 randomized controlled trials with a total of 3,613 individuals with obesity who did not have diabetes. The mean difference in weight reduction was -11.85%, favoring semaglutide [95% confidence interval (CI) (-12.81,-10.90), p<0.00001]. Secondary outcomes showed that gastrointestinal adverse events were 1.59 times more likely with semaglutide (RR 1.59, 95%CI [1.34, 1.88], p<0.00001). Discontinuation due to adverse events was twice as likely in the semaglutide group (RR 2.19, 95%CI [1.36,3.55], p=0.001), and serious adverse events were 1.6 times more likely with semaglutide (RR1.60, 95%CI [1.24, 2.07], p=0.0003). Serious events were mostly gastrointestinal and hepatobiliary disorders, such as acute pancreatitis and cholelithiasis. Among individuals with obesity without type 2 diabetes, subcutaneous semaglutide is effective for weight loss, with an 11.85% reduction from baseline compared with placebo.

Aim of the study: Semaglutide, a glucagon-like peptide-1 receptor agonist, has demonstrated clinically important weight loss effects in patients with type 2 diabetes. However, its effects on sustained weight loss in patients without diabetes remains unclear.

Results: Compared with placebo, semaglutide use was associated with substantial decreases in long-term relative (WMD -12.1%, 95% CI -13.5 to -10.7) and absolute body weight (WMD -12.3 kg, 95% CI -13.6 to -11.0). At the longest follow-up, 33.4% of participants randomized to semaglutide achieved ≥20% weight loss, compared with 2.2% with placebo (RR 15.08, 95% CI 9.31 to 24.43). The risk of gastrointestinal adverse events was higher in participants who took semaglutide than in those who took placebo (RR 1:47, 95% CI 1.28 to 1.68); however, most of these events were transient and mild to moderate in severity and did not require treatment discontinuation. In conclusion, semaglutide is effective for sustained weight loss in patients with overweight/obesity who do not have diabetes.

Aim of the study: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), initially developed for type 2 diabetes mellitus, show promise in promoting weight loss and improving heart health in obese individuals without diabetes. Our goal was to examine existing research for conclusive evidence on various types of GLP-1 RAs for weight loss and cardiometabolic benefits in obesity without diabetes.

Results: Our search yielded a total of 7535 articles. We included 15 trials in our study. GLP-1 RAs led to significant weight loss (MD, -8.77 kg; P <.01) in obese individuals. GLP-1 RAs also improved systolic BP (MD, -4.13 mm Hg; P <.01), diastolic BP (MD, -1.39 mm Hg; P <.01), and lipid profiles, including improved levels of triacylglycerol (SMD, -0.99 mg/dL; P <.01), total cholesterol (SMD, -0.73 mg/dL; P <.01), very low-density lipoprotein (SMD, -1.11 mg/dL; P <.01), and low-density lipoprotein (SMD, -0.27 mg/dL; P <.01), and significantly increased high-density lipoprotein levels (SMD, 0.11 mg/dL; P <.01). However, GLP-1 RAs were associated with an increased risk of gastrointestinal adverse events. GLP-1 RAs were found to be beneficial not only for weight loss but also for reducing cardiovascular disease risk factors such as BP and lipid profile. Consistent beneficial results were observed across the various subtypes of GLP-1 RAs.

Aim of the study: To explore the safety and efficacy of subcutaneous semaglutide 2.4 mg, administered once a week in non-diabetic overweight or obese individuals.

Results: Six RCTs comprising 3962 overweight or obese individuals were identified. The findings indicated that, in comparison to the placebo group, semaglutide caused a significant and sustainable reduction in the percentage of body weight (BW; mean difference [MD]: -11.80% [95% confidence interval {CI} -12.93, -10.68]; P < 0.00001) as well as a decrease in absolute BW (MD: -12.2 kg [95% CI -13.3, -11.1]; P < 0.00001), body mass index (MD: -4.5 kg/m2 [95% CI -4.9, -4.1]; P < 0.00001) and waist circumference (MD:-9.4 cm [95% CI -10.1, -8.8]; P < 0.00001). Moreover, it achieved a higher proportion of patients who experienced weight loss exceeding 5%, 10%, 15% and 20%. Furthermore, semaglutide showed significant efficacy in controlling blood pressure, blood sugar levels, C-reactive protein levels, and lipid profiles.

Aim of the study: The goal of obesity management is to improve health. Sustained weight loss of more than 10% overall bodyweight improves many of the complications associated with obesity (eg, prevention and control of type 2 diabetes, hypertension, fatty liver disease, and obstructive sleep apnoea), as well as quality of life.

Results: These highly effective anti-obesity medications are associated with weight losses of more than 10% of overall bodyweight in more than two-thirds of clinical trial participants. Long-term data on safety, efficacy, and cardiovascular outcomes are awaited. Long-term studies have shown that bariatric surgical procedures typically lead to a durable weight loss of 25% and rapid, sustained improvements in complications of obesity, although they have not yet been compared with new-generation highly effective anti-obesity medications. Further work is required to determine optimal patient-specific treatment strategies, including combinations of lifestyle interventions, anti-obesity medications, endoscopic and bariatric surgical procedures, and to ensure equitable access to effective treatments.