Semaglutide is a GLP-1 receptor agonist, sharing an astounding 94% structural homology with the human hormone. It activates these receptors in the gastrointestinal tract, pancreas, and hypothalamus to mitigate sensations of hunger and food cravings and enhance feelings of satiety. Click here to Learn More.
During SUSTAIN 3, participants receiving subcutaneous semaglutide (Wegovy(r)) experienced weight loss greater than placebo. These results were consistent across the two extensions.
The drug helps people lose weight and keep it off for at least four years. Several studies have also shown that it reduces heart disease risk in overweight and obese adults without diabetes. It has also been shown to improve symptoms of heart failure, such as tiredness and shortness of breath. In addition, it can improve exercise tolerance and decrease swelling in the legs. Moreover, it has been shown to reduce the risk of diabetes-related kidney damage.
The new study, published in the journal Nature Medicine, examined SELECT trial data and found that once-weekly semaglutide reduced both relative and absolute body weight in people with overweight or obesity without diabetes. It also reduced waist size, a marker of central fat distribution associated with cardiovascular risk. The results were similar to those of other trials, and the treatment was well tolerated.
Side effects from taking the medication include nausea, stomach upset, vomiting, and diarrhea. However, these symptoms usually disappear as your body adjusts to the medication. If these symptoms don’t go away, talk to your doctor. Your doctor may monitor your kidney function and give you other medications to prevent kidney damage from occurring.
Semaglutide is a powerful medication that is used to treat type 2 diabetes and obesity. It has been shown to reduce the risk of heart attack and stroke in people with high blood pressure, high cholesterol levels, and a history of diabetes or heart disease. It also reduces inflammation and oxidative stress, which can help protect the brain.
Cardiovascular risk reduction
As the first GLP-1 agonist to be approved for non-diabetes use, Semaglutide is expected to significantly reduce cardiovascular risk in people who have preexisting CVD but do not have diabetes. The SELECT (Semaglutide Eating and Living Well with Cardiovascular Disease Treatment Evaluation) trial, published in the journal Nature Medicine, found that weekly subcutaneous injections of semaglutide reduced the risk of major adverse cardiovascular events (MACE) by 20% over two years compared to placebo.
The randomized, double-blind, placebo-controlled study enrolled 17,604 adults with a body mass index (BMI) over 27 and at least one weight-related comorbidity without diabetes and randomly assigned them to receive either semaglutide or placebo as part of their regular medical care for two years. The primary cardiovascular end point was a composite of cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke in a time-to-first-event analysis. The researchers also measured changes in glycated hemoglobin level, body weight, and systolic blood pressure over the same time period.
Yale medicine cardiologist Harlan Krumholz, MD, SM, who led the SELECT trial, says that the new data confirm that semaglutide (marketed as Ozempic by Novo Nordisk) reduces heart disease risk in people with obesity and without diabetes. He estimates that 6.6 million Americans, or about a quarter of the adult population, meet those criteria, making them eligible to benefit from the medication. The findings support the FDA’s decision to approve it for this use.
Glycemic control
A new study based on the SELECT trial, which analyzed participants who completed treatment in the main phase, found that semaglutide continued to be associated with significant reductions in body weight and cardiometabolic risk factors. Researchers also discovered that the benefit is consistent across different groups of patients with HFpEF and obesity. The study is published in Nature Medicine.
The SELECT study was designed to measure the effects of once-weekly semaglutide 2.4 mg versus placebo on health outcomes in people with heart failure and obesity. The study included 17,604 adults with a body mass index of 30 kg/m2 or higher who were randomly assigned to receive either semaglutide or placebo for 68 weeks. The results showed that semaglutide significantly reduced body weight and cardiovascular risk factors compared with placebo.
Among people with diabetes, semaglutide reduced the risk of major adverse cardiovascular events and death by 26% compared with placebo. The same results were seen in the SELECT extension, which was conducted at five sites in the United States and three in Japan.
In addition to helping with weight loss, semaglutide also reduces blood sugar levels in people with type 2 diabetes by encouraging the body to use its own insulin better. The drug can also help people with diabetes maintain a healthier bodyweight and avoid kidney damage, which is often a problem in people with diabetes. It can be used along with a low-calorie diet and increased physical activity.
Gastrointestinal adverse effects
The GLP-1 agonist effect on the stomach is responsible for slowing the rate at which food moves from the stomach to the small intestine, which creates a feeling of fullness and reduces overall food intake. It also slows the absorption of sugar from the gastrointestinal tract into the bloodstream. This combination of actions prevents rapid spikes in blood glucose after meals and contributes to weight loss and reduced cardiovascular risk.
The most common side effects of semaglutide are nausea and vomiting, diarrhea, stomach pain, constipation, and fatigue. These symptoms usually improve as the body gets used to the medication. However, patients should be aware of the possible risk of more severe gastrointestinal adverse effects such as pancreatitis, gallbladder disease, and kidney damage.
Patients who take this medication should be careful not to drink too much water or fluids, as this can cause dehydration. They should tell their doctor if they have any signs or symptoms of dehydration such as unusually dry skin, thirst, or fever. In addition, they should tell their doctors if they have a history of pancreatitis, gallbladder, or kidney disease, or have recently undergone bariatric surgery.
In a recent study, patients who received semaglutide lost more weight than those who took placebo after 104 weeks. They also had lower blood pressure, improved cholesterol levels, and fewer heart problems. However, the study did not address whether the weight loss was a result of the medication or due to other factors.
Adverse events
The adverse effects of Semaglutide on the body are minimal, but patients should be counseled about the possibility of gastrointestinal side effects and monitored closely for signs and symptoms. Physicians and other healthcare professionals should encourage their patients to report any observed adverse events promptly. This enables them to inform the patient of possible interventions that can be taken to alleviate or prevent the adverse effects, including dose adjustments and discontinuation of treatment.
In the clinical trials of semaglutide, gastrointestinal adverse events such as nausea, diarrhea, vomiting and constipation occurred in more participants treated with the drug than those receiving placebo (see Extended Data Fig. 7). Nevertheless, the majority of these gastrointestinal events were mild to moderate and transient, and none led to permanent treatment discontinuation in the semaglutide group.
Another possible adverse effect of this GLP-1 receptor agonist is acute kidney injury. The underlying mechanism is fluid depletion, which can be caused by nausea, vomiting and diarrhea, or by a combination of these factors. The risk of this side effect is increased in those who are taking medications that cause a significant amount of fluid loss, such as diuretics.
Other potentially serious adverse reactions from this medication include severe allergic reactions (anaphylaxis), liver damage, pancreatitis and gallbladder disease. In addition, this drug should not be used by people who are pregnant or breastfeeding. Patients should also tell their doctor about any other prescription and nonprescription medications, vitamins, nutritional supplements and herbal products they are taking.
Overdose
In some cases, taking too much Semaglutide can lead to complications including pancreatitis and kidney problems. You should seek medical attention immediately if you have symptoms such as severe stomach pain that won’t subside or changes in urine output. Heart palpitations and a fast heartbeat are also possible signs of an overdose.
While these side effects are rare, they can be dangerous if left untreated. Semaglutide has a half-life of about one week, so it takes time for the drug to clear out of your system. The most common overdose symptoms include gastrointestinal problems such as nausea and vomiting, which can cause dehydration and nutrient malabsorption.
Poison centers around the US are seeing a steep increase in calls related to this drug, but it’s not necessarily because of an accidental overdose. Rather, it’s because people are obtaining compounded semaglutide from illegal online pharmacies and aesthetic spas. In these cases, the compounded semaglutide is injected into a multidose vial instead of a pen injector like Ozempic or Wegovy. This is not a good idea because the drug needs to be administered with a sharp needle, and this increases the risk of errors.
It is also important to note that the FDA-approved version of semaglutide is only available from Novo Nordisk in a pen injector. Compounding pharmacies may sell a generic form of the medication, but this should only be done under a doctor’s supervision.