A once-weekly analogue of human glucagon-like peptide-1 (GLP-1), for the treatment of adults with type 2 diabetes.

Tradename Ozempic, Wegovy, Rybelsus.

Bioavailability 89%.

Metabolism by Proteolysis

Elimination half-life 1 week.

Duration of action 63.6 h

Excretion by Urine and feces.

It lowers the blood sugar level by increasing the production of insulin.

It reduces hunger, food craving and body fat.

Chemically similar to glucagon-like peptide-1 (GLP-1).

As a GLP-1 analog and functions as a GLP-1 agonist.

In the PIONEER 3 trial Semaglutide, the first oral preparation of a GLP-1RA, resulting in greater glucose lowering and weight loss compared with sitagliptin.

PIONEER 6 study involving patients with type two diabetes, cardiovascular risk profile of oral semaglutide was not inferior to placebo.

2.4 mg of semaglutide subcutaneously once weekly plus lifestyle style intervention in obese patients was associated with sustained, clinically relevant reduction in body weight (Wilding JP).

Semglutide and other GLP-1 (Glucagon like peptide 1) agents provide weight loss by improved appetite control, reduced energy intake via the hypothalamus and area post stream of the brain.


Among adults with overweight or obesity completing a 20 week run of subcutaneous semaglutide results and continued weight loss.

Semaglutide Treatment resulted in significant high percentage of patients with NASH resolution than placebo, but did not show significant difference in the percentage of patients with improvement in fibrosis stage.

In patients with heart failure with preserved ejection fraction and obesity, treatment with Semaglutide, lead to larger reductions in symptoms and physical limitations, greater improvements in exercise function, and greater amount of weight loss than placebo (STEP-HFpEF trial).

Semaglutide provides benefits for patients with heart failure with preserved ejection fraction through an upstream intervention that addresses metabolic drivers and differs from earlier treatment approaches that aim to reduce myocardial load, or induce neurohormonal blockade.

Semaglutide seems to be particularly beneficial, when patients with insulin resistance have low endogenous levels of GLP-1.

GLP – 1 agonism has broad effects: redistributes fat, decreaseinflammation, inhibits glucagon production, and delays gastric emptying.

Among adults with overweight or obesity without diabetes once weekly subcutaneous semaglutide compared with once daily subcutaneous liraglutide resulted in significantly greater weight loss at 68 weeks.

Among adolescents with obesity, once weekly treatment with a 2.4 mg dose of Semaglutide plus lifestyle intervention resulted in greater reduction in BMI than lifestyle intervention alone (STEPTEENS investigators).

Findings from a multi-center, international clinical trial showed that semaglutide reduced cardiovascular events by 20% in adults with overweight or obesity and established cardiovascular disease who don’t have diabetes. 

In the trial, patients treated with semaglutide lost an average of 9.4% of their body weight and experienced improvements in other risk factors for cardiovascular disease. 

In the trial, for patients with preexisting cardiovascular disease and overweight or obesity but without diabetes, weekly injections of semaglutide at a dose of 2.4 mg was superior to placebo in reducing the risk of death from cardiovascular causes, nonfatal heart attack, or nonfatal stroke over an average follow-up of 40 months. 

High body-mass index (BMI) is estimated to have accounted for 4 million deaths globally in 2015, more than two thirds of which were caused by cardiovascular diseases.  

Semaglutide, a GLP-1 receptor agonist medication initially approved and most frequently prescribed for adults with type 2 diabetes, was also FDA-approved in 2021 for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity. 

Weight loss effects of semaglutide appear to occur primarily through appetite suppression, this drug has other actions which may reduce cardiovascular risk, including improvements in glucose levels, decreases in blood pressure and cholesterol levels and reductions in inflammation, and beneficial effects on heart muscle and blood vessels.  

In the SELECT trial, over 17,000 patients in 41 countries who had previously experienced a heart attack, stroke and/or had peripheral artery disease were enrolled and followed for an average of 40 months after being randomly assigned to receive once weekly injections of semaglutide 2.4 mg or placebo.  

Death from a cardiovascular event, nonfatal myocardial infarction, or nonfatal stroke occurred during the trial in 6.5% of patients who were treated with semaglutide versus 8.0% of patients who received placebo -a 20% reduction in relative risk by semaglutide. 

Risk reductions were similar in men and women and across different ethnicities, patient ages and baseline levels of bodyweight. 

More patients discontinued semaglutide (16.6%) than placebo (8.2%), due primarily to gastrointestinal symptoms including nausea and diarrhea. 

There was a slightly higher rate of gallbladder disorders in the semaglutide vs. placebo group (2.8% vs. 2.3%, respectively), which has also been previously reported in other studies with GLP-1 agents. 

Importantly, semaglutide was not associated with higher risks for severe gastrointestinal disorders, pancreatitis, psychiatric disorders or kidney injury. 

The effects of semaglutide on primary prevention of cardiovascular events in persons with overweight or obesity, but without previous cardiovascular disease, were not studied. 

In patients with pre-existing cardiovascular disease and obesity, but without diabetes, weekly subcutaneous, semaglutide at a dose of 2.4 mg was superior to placebo in reducing the incidence of death from cardiovascular causes, non-fatal, myocardial infarction, or non-fatal stroke at a mean, follow up of 39.8 months (SELECT trial investigators).

After approximately 40 months of follow up in the SELCT trial, Semaglutide resulted in a 20% reduction in the risk of a composite of deaths from cardiovascular causes, non-fatal myocardial infarction, or non-fatal, stroke, as well as for death from any cause.

Oral Semaglutide available in 7, and 14 mg tablets (Rybelsus).

The most common adverse events are a G.I. issues, including nausea, vomiting, diarrhea, and constipation.

Recent findings found increased risk for pancreatitis, bowel obstruction, gastroparesis, biliary disease, lung aspiration with anesthesia.


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