Subjects with biopsy-confirmed NASH and cirrhosis were randomized (2:1) to receive subcutaneous once-weekly semaglutide or visually matching placebo. Patients, investigators and outcome assessors were masked to treatment assignment. Contact Semaglutide San Diego now!
Compared to placebo, semaglutide led to lower ad libitum energy intake at lunch and from evening meal and snacks and to greater reductions in appetite parameters, thirst and nausea ratings.
Patients with Type 2 Diabetes can benefit from the multiple benefits of Semaglutide. This medication helps lower blood sugar levels, reduces weight and improves risk factors for heart disease. Additionally, Semaglutide can help lower cholesterol levels and improve quality of life for these patients.
The drug works by mimicking the effects of natural GLP-1 hormones in the body. It binds to and activates the GLP-1 receptors in the pancreas, encouraging insulin production and lowering blood sugar. It also suppresses the release of glucagon, another pancreatic hormone that raises blood sugar levels.
This medication is available by prescription only. Your doctor will determine your dosage based on your weight, medical history and other health conditions. It is usually taken by mouth, but can also be injected under the skin. It is important to monitor your blood sugar levels frequently, especially after injections.
If you are not achieving your target blood sugar level, your doctor may adjust your dose or switch you to another medication. This medication should be used as part of a comprehensive treatment plan that includes diet, exercise and weight loss. You should tell your doctor if you have any side effects, such as a feeling of constant hunger or vomiting. You should also report any eye changes or other symptoms to your doctor.
Novo Nordisk produces three medications, Ozempic, Wegovy and Rybelsus, that contain the drug semaglutide. The FDA approved the medication for oral administration in September 2019 and is available in 3-, 7-, and 14-mg tablets. It is recommended that you begin treatment with the 3-mg dose and then increase to the 7-mg dose after 30 days. If you need additional glycemic control, your doctor can prescribe the 14-mg tablet.
The PIONEER 4 trial demonstrated that oral semaglutide was as effective as subcutaneous liraglutide added to background metformin in lowering A1C and promoting weight loss in patients with type 2 diabetes. This is the first time that a drug from this class has been shown to be effective when administered orally. The drug’s oral administration route is particularly beneficial for patients who are unable or unwilling to self-administer an injectable medication.
The development of drugs that can treat NASH and its associated cirrhosis is a priority for the pharmaceutical industry. A drug that can reduce liver fat and improve fibrosis is a significant advance for NASH treatment. Two candidates are currently in clinical trials: obeticholic acid (OCA) and pegozafermin. Both are oral farnesoid X receptor (FXR) agonists. OCA was leading the race to become the first approved drug for NASH until it failed to meet the primary histology endpoint in the phase 3 REGENERATE trial. The FDA rejected the drug’s new drug application in June 2020.
Semaglutide was also shown to reduce liver fat in a phase 2 study of patients with NASH and compensated cirrhosis. In this double-blind, placebo-controlled study, patients with biopsy-confirmed NASH were assigned to receive either once-weekly subcutaneous semaglutide 2.4 mg or placebo. Patients were followed for 72 weeks. Histologic assessments were performed on pre-treatment and post-treatment liver biopsies. The assessments were made by two independent expert hepatopathologists who were unaware of treatment allocation, patient characteristics, or each other’s assessments. Improvement of NASH activity score without worsening of fibrosis was the primary efficacy endpoint.
NASH resolution with no worsening of fibrosis was achieved in 40% of the patients receiving semaglutide 0.1 mg, 36% of the patients receiving semaglutide 0.2 mg, and 59% of those receiving semaglutide 0.4 mg, compared with 17% of placebo-treated patients. In addition, the drug significantly reduced hepatic steatosis and lobular inflammation as well as improved Pro-C3 levels and liver stiffness, as measured by magnetic resonance elastography.
Gastrointestinal adverse events were the most common side effects, occurring in 7% of patients in the semaglutide groups and 5% of those in the placebo group. Rencofilstat, a cyclosporine A analog, inhibits FXR signaling and thus limits the activation of hepatic stellate cells, which can lead to fibrosis progression in NASH. It is currently being tested in the ASCEND phase 2b trial.
Cirrhosis is a serious condition that occurs when your liver is scarred and can’t function properly. It’s a major risk factor for liver cancer and death, and it can lead to hepatitis C infection, which is also a major health problem that requires treatment with Interferon and Ribavirin.
The GLP-1 agonist semaglutide is being tested for its ability to prevent or treat the progression of NAFLD to cirrhosis in people with type 2 diabetes. NAFLD is caused by excess fat in the liver that can cause inflammation and damage to the liver cells. If left untreated, it can develop into nonalcoholic steatohepatitis (NASH) and eventually lead to cirrhosis, which is a permanent change in the structure of your liver and is a major risk factor for liver disease, including liver cancer.
A recent double-blind, placebo-controlled phase 2 trial published in the Lancet Gastroenterology & Hepatology enrolled 71 patients with biopsy-confirmed NASH and a body mass index (BMI) of 35 kg/m2 or higher. Participants were randomly assigned to receive once-daily subcutaneous semaglutide at doses of 0.1, 0.2, or 0.4 mg and placebo. The study was designed to measure the rate of liver fibrosis regression in patients with NASH and compensated cirrhosis, as well as its impact on the development of hepatocellular carcinoma (cancer of the liver) and other measures of organ function.
In this study, people with NASH and cirrhosis who took the highest dose of semaglutide had the lowest rates of hepatocellular carcinoma. The rate of hepatocellular carcinoma was almost 50% lower in the group that received the 0.4 mg dose compared to the group that received the 0.1mg dose and was 20% lower in the placebo group.
However, in some studies of oral semaglutide, the drug can cause gastrointestinal side effects, including nausea, vomiting, constipation, decreased appetite, and abdominal pain. These effects usually occurred during the first few weeks of therapy. To help reduce these side effects, you should take the medication with food and drink that are high in fat or protein to increase gastrointestinal absorption and decrease the likelihood of these side effects.
Semaglutide can help with weight loss by blocking your body’s ability to absorb calories and sugar. It also slows the rate at which food moves from your stomach to your small intestine, giving you a feeling of fullness and reducing overall calorie intake.
The manufacturer of the drug reports that over 68 weeks, those taking it lost an average of 35 lbs (15 kg) and nearly 15% of their body weight. The drug was significantly more effective than placebo. It was also found to improve cardiometabolic risk factors like waist circumference, systolic blood pressure and glycated hemoglobin levels as well as overall quality of life.
A key to successful weight loss with the medication is consistent adherence. Patients should take it at the same time each day with a glass of water and after a meal to ensure proper absorption. They should also talk to their doctor if they have any concerns or experience side effects such as nausea, vomiting or diarrhea. If they do, their doctor may lower the dosage or switch them to a different type of pill.
You should always tell your doctor if you are pregnant, breastfeeding or have any kidney or liver problems. The manufacturer of the drug has also reported that certain medical conditions, such as medullary thyroid cancer or multiple endocrine neoplasia type 2 (MEN 2), increase your risk of side effects from the medication. Additionally, you should avoid excessive alcohol consumption and smoking, as these can cause pancreatitis.
Your doctor may prescribe the medication off-label for a condition other than those listed above, but it should only be done after a thorough patient evaluation and careful consideration of the benefits and risks. It is also important to keep your doctor informed of any changes in your diet, exercise or medications.
You should also tell your doctor if you have any mental health issues or are having suicidal thoughts, as these can be serious and require immediate medical attention. It’s also a good idea to let your doctor know about any family history of pancreatitis, gallbladder problems, kidney disease or thyroid tumors.
