Obesity is one of the leading public health problems in the 21st century. It has a clear association with type 2 diabetes mellitus (DM2) and cardiovascular (CV) diseases, leading to a reduction in life expectancy. Despite its importance, there have been few therapeutic advances in the management of obesity in recent years.
What is it Semaglutide?
Semaglutide is a glucagon-like peptide-1 (GLP-1) analog approved for the treatment of DM2. In addition to having a powerful hypoglycemic effect, it can reduce CV events in patients with DM2 with high CVR.
Is Semaglutide Good for Weight Loss?
Semaglutide also has another series of beneficial effect, including weight loss. Weight loss with Semaglutide in the SUSTAIN research program in DM2 reached up to 7 kg in the studies with the most extended follow-up with the 1 mg/week dose. Still, phase II studies conducted on obese subjects showed greater potency in weight reduction with good clinical tolerance using higher doses.
The STEP 1 study was a multicenter, randomized, double-blind clinical trial conducted at 121 centers in 16 countries. It included 1961 subjects with obesity (body mass index [BMI] ≥ 30 or BMI ≥ 27) with some associated risk factors but without DM2.
Patients were randomized 2:1 to receive Semaglutide 2.4 mg/week or placebo and healthy diet and exercise recommendations in both groups. The study’s primary endpoints were the percent change in body weight at 68 weeks and the percentage of subjects who reduced their body weight by at least 5%. Novo Nordisk funded the study.
The mean age of the included patients was 46 years, and 76% were women. The mean baseline BMI was 37.9, and 44% of the patients had prediabetes. Percentage weight loss was −14.9% with Semaglutide vs −2.4% with placebo (difference −12.4%; p < 0.001). More Semaglutide-treated patients lost at least 5% of their body weight (86.4% vs. 31.5%; p < 0.001), noting that half of Semaglutide-treated patients achieved a 15% or more weight loss at 68 weeks, versus only 5% with placebo (p < 0.001).
Secondarily, other benefits note that Semaglutide reduces blood pressure, basal blood glucose, lipid profile, or improvement in physical fitness.
Who Should not take Semaglutide?
In an exploratory analysis Semaglutide treatment was safe, although gastrointestinal adverse events (nausea, vomiting, diarrhea) were more frequent with Semaglutide (74% vs. 48%). These adverse events were mild or moderate in intensity in most patients. There were 3 cases of acute pancreatitis with semaglutide (0.2%), mild intensity, and a higher incidence of cholelithiasis (1.8% vs. 0.6%).
The authors concluded that in overweight or obese adults without DM2, weekly subcutaneous Semaglutide treatment and lifestyle intervention were associated with sustained and clinically relevant weight loss (ClinicalTrials.gov, NCT03548935). “In adults with obesity or overweight but without DM2, weekly treatment with subcutaneous Semaglutide. Plus intervention in lifestyle habits was associated with sustained and clinically relevant weight loss over time.”
What does Semaglutide do to your Body?
Obesity is a significant public health problem. Although the ideal treatment is prevention, few pharmacological treatments have demonstrated efficacy and safety once established. Semaglutide is a hypoglycemic drug with known efficacy for metabolic control and reducing CV events in patients with DM2. It is probably the most effective GLP-1 analog for weight loss. Its weekly administration also made it an exciting option for treating obesity, as seen in STEP 1.
Semaglutide Weight loss Reviews
Weight reduction was observed early at four weeks, reaching a nadir at 60 weeks of follow-up, and sustains over time. The results were very positive, showing a powerful effect on weight loss. The change in body weight at 68 weeks with semaglutide was −15.3 kg.
In the study, only a minority of the patients included had a history of CV disease (2%), so its applicability to patients with established CV disease is unknown. A phase III clinical trial is currently evaluating the efficacy of Semaglutide 2.4 mg/week versus placebo in reducing major cardiovascular events in patients with BMI ≥ 27 and established CV disease but without DM2 (NCT03574597).
Another clinical trial, for example, is assessing the efficacy of this drug in the treatment of heart failure with preserved systolic function. GLP-1 analogs have additional positive effects on weight loss, both at a metabolic and cardiovascular level, improving the lipid profile, lowering blood pressure.
The dose used was higher than the dose approved for its indication in DM2. It is important to remember that the starting dose was 0.25 mg per week. There was a gradual increase (0.5-1-1.7 mg) every four weeks until the target dose was complete. Suppose the drug achieves the indication for the treatment of obesity. In that case, it is essential to maintain this titration scheme in clinical practice.
Although the drug was safe, 75% of patients had gastrointestinal symptoms, with nausea being the most common side effect even with this careful titration. However, we should note that only 7% led to drug discontinuation. The high cost of the drug may be a limitation for its widespread use in clinical practice with this indication.