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Improving Cardiometabolic Risk Factors and Function

Sustained weight loss results in improvements in cardiometabolic risk factors and function. This is especially important for people with obesity-related chronic conditions.

During run-in, participants received once-weekly injections of semaglutide (2.4 mg) and followed an individualized diet and lifestyle regimen. They were then randomized to continue receiving semaglutide or placebo for 68 weeks. Contact Semaglutide San Diego now!

In clinical trials, semaglutide has proven effective in helping individuals lose weight. In a 2021 phase 3 trial, 2.4 milligram weekly injections of semaglutide produced a mean weight loss of 14.9% after 68 weeks when compared to a placebo in individuals with type 2 diabetes and an elevated body mass index (BMI) of 27 or more. This led to FDA approval in June of 2021 of injectable semaglutide under the brand name Wegovy for chronic weight management in people with or without diabetes.

Like other medications that help individuals lose weight, semaglutide works by reducing appetite and lowering caloric intake. It also slows stomach emptying, leading to prolonged feelings of fullness after eating and reducing the inclination to overeat.

Semaglutide may interact with a number of medications, including blood thinners and other anti-diuretics; it is important to inform your doctor of all current medications you are taking. The medication can also cause side effects such as nausea, vomiting, diarrhea and constipation. It can also increase your blood sugar levels and you should tell your care team if you develop hypoglycemia, a dangerous low glucose level.

Individuals with serious liver or kidney problems, a history of pancreatitis, or a condition such as medullary thyroid cancer or multiple endocrine neoplasia type 2 should not take semaglutide. It is also not safe for pregnant women, and it is not recommended to use this medication if you have certain types of depression or suicidal thoughts.

Considering its efficacy for treating obesity, semaglutide is typically prescribed as part of a comprehensive treatment plan that includes dietary and exercise changes. It’s important to discuss your goals with your doctor and work together to develop a plan that will help you reach your target weight.

Semaglutide is an expensive medication and you will need to discuss insurance coverage with your provider before starting it, says Dr. Saunders. Additionally, you should be comfortable with the idea of being on the medication long-term, since obesity is a chronic disease. Patients who are unable to obtain coverage for the medication can sometimes find it by asking their local pharmacist to compound the drug, which is the process of combining, mixing or altering ingredients to create a tailored medication.

Cholesterol Lowering

The GLP-1 agonist drugs in the injectable class, including semaglutide, have been shown to significantly reduce levels of cholesterol and triglycerides in patients with type 2 diabetes. These effects are due to the binding of GLP-1 to the GPR40 receptor on the gut, reducing gastrointestinal secretions and increasing satiety and calorie burn. Semaglutide has also been shown to improve insulin sensitivity and reduce overall inflammation in the body.

In the STEP 5 trials, semaglutide 2.4 mg significantly improved multiple cardiometabolic parameters compared to placebo (eg, waist circumference, systolic blood pressure, total and low-density lipoprotein cholesterol, very-low-density lipoprotein cholesterol). This was observed regardless of background OAD treatment. The rate of hypoglycaemic events was lower with semaglutide compared to the comparator groups. In general, the safety profile of semaglutide was consistent with the other trials in the STEP program6,7,9,16 and with other GLP-1 agonists in general.

Serious adverse events leading to discontinuation of the trial drug were less common with semaglutide compared to the comparators, but occurred in more than two percent of all subjects treated. Gastrointestinal disorders were most commonly reported with the semaglutide group and were typically transient, mild to moderate in severity, and did not lead to treatment discontinuation. Malignant neoplasms were reported in four subjects with semaglutide and in two subjects with dulaglutide, but none of these were considered to be related to the trial product by an independent external event adjudication committee.

TRICARE covers anti-obesity medications, including semaglutide (Ozempic), if they meet the prior authorization criteria. Service Members should discuss any operational, training, or deployment implications with their military medical provider and ensure that all of their medications are recorded in the electronic health record.

The FDA approved the Novo Nordisk’s product, semaglutide injection (Ozempic), in 2017. It is available by prescription only. It is given by injection under the skin in the upper leg (thigh) or stomach area, usually once per week. Be sure to use only the prescribed dosage and change (rotate) injection sites each time. Check the RxList Drug Interaction Checker for more information on avoiding interactions. The Food and Drug Administration (FDA) is responsible for ensuring the safety, efficacy, and security of medical devices, foods, vaccines, medicines, and cosmetics. The FDA’s website includes information about reporting problems and finding help.

Blood Sugar Lowering

Semaglutide is a type 2 diabetes medication that can be taken orally (Rybelsus) or by a once-per-week prefilled injection pen that is self-administered subcutaneously (under the skin) (Ozempic). It mimics the effect of GLP-1, a naturally occurring hormone released by your gut when you eat. GLP-1 stimulates insulin release to drive blood sugar into cells where it can be used for energy. In addition, GLP-1 slows the stomach’s emptying to promote a feeling of fullness. This prevents overeating and can contribute to weight loss.

Semaglutide also lowers blood sugar levels by preventing the release of glucagon, another hormone that elevates blood sugar. It inhibits the liver’s production of glucagon, which reduces blood sugar by forcing your body to use its stored glucose for energy. Combined, this helps maintain stable blood sugar levels and reduces the hunger pangs that often occur when blood sugar drops too low.

In a study of diabetic patients, semaglutide reduced A1C by 7.6 points on average. It also lowered weight, waist circumference, and systolic blood pressure. Researchers noted that a combination of semaglutide and a healthy diet and exercise routine was more effective than other diabetes medications at reducing these risk factors.

Unlike many other diabetes medications, semaglutide does not cause hypoglycemia (low blood sugar). It is considered safe for pregnant women. However, it has not been adequately studied in pregnant women and should be used only when the potential benefits outweigh the risks of uncontrolled diabetes, which include preeclampsia, spontaneous abortion, or preterm delivery.

A recent study sponsored by the drug’s manufacturer found that semaglutide significantly lowered cardiovascular disease risk in people with obesity and heart failure. It decreased symptoms like fatigue and shortness of breath and improved overall physical function. Semaglutide can be prescribed “off-label” to treat other conditions, if the doctor feels it will benefit the patient.

Taking semaglutide may interact with several medicines including ACE inhibitors, diuretics, and some anti-seizure medications. It is not recommended for pregnant women, breastfeeding mothers, or anyone who has a serious kidney or liver problem. It has also been reported to be habit forming.

Cardiovascular Health

In addition to helping people lose weight, semaglutide appears to reduce heart disease risk factors. In the SELECT trial, which was sponsored by Novo Nordisk, which makes semaglutide, researchers found that people who took it had lower cholesterol levels and less systolic blood pressure (the top number of your heart rate) than those who did not take the medication. Semaglutide also significantly reduced blood sugar and blood fats.

A similar study found that the drug lowers blood pressure and helps prevent heart attack, stroke, and other cardiovascular events in people with type 2 diabetes who have coronary artery disease or other risk factors for those problems. The newest findings suggest that the same benefits may apply to people who are overweight and do not have diabetes, but who have a higher-than-average risk for heart disease.

The SELECT researchers analyzed results from the first two double-blind, placebo-controlled trials (STEP 1 and STEP 4), which involved participants with obesity without diabetes who were at high risk for cardiovascular disease. They compared the effects of once-weekly subcutaneous injections of semaglutide versus placebo for 68 weeks. The primary endpoint was the composite of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke. Other secondary endpoints included changes in waist circumference, systolic and diastolic blood pressure, fasting serum insulin, and HOMA-IR.

In the randomized studies, the researchers observed that at week 68, semaglutide significantly reduced systolic and diastolic BP, as well as fasting glycemia and total lipids (see Table S3). In addition, a greater proportion of the participants taking semaglutide achieved their ACC/AHA BP target than did those on placebo (i.e., 130/80 mmHg).

The researchers conclude that the SELECT data provide “evidence of substantial secondary cardiovascular benefit with long-term treatment of patients with obesity and no history of diabetes with semaglutide.” But they note that more research is needed to understand how the drug achieves these benefits in people without diabetes, and whether the reductions in heart disease risk factors are just a side effect of the weight loss associated with semaglutide. As many as 6.6 million Americans fit that criteria, and it is important to know how the drug could help them avoid heart disease.