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Semaglutide: A Paradigm Shift In Metabolic Disorders?

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Is Semaglutide a paradigm shift in the treatment of metabolic illnesses? If you want to find the answer to this question, keep reading!

Research shows that type 2 diabetes (T2D) and obesity may be treated with Semaglutide since it is a glucagon-like peptide 1 receptor (GLP-1). Semaglutide is the first molecule of this family accessible in oral formulation for T2D treatment, providing a valuable alternative for subjects and doctors hesitant to begin the medicine because of its stronger effect on glycated hemoglobin (HbA1c) decrease compared to other GLP-1 RAs. According to studies, Semaglutide is intended to revolutionize the treatment of obesity, even in those who do not have diabetes, since it has weight-loss effects superior to those of other GLP-1 RAs and is comparable to those of bariatric surgery. 

Semaglutide, like other GLP-1 RAs, also has good effects on cardiovascular (CV), renal, and liver protection, making it a promising medication for the treatment of “diabesity” (the co-occurrence of diabetes and obesity) and related co-morbidities, as per clinical trial results.

Introduction

The goal of treating type 2 diabetes (T2D) is to keep a healthy blood sugar level while also decreasing the risk of developing long-term problems.

Research shows that the first-line medications in the current multifactorial approach to type 2 diabetes are glucagon-like peptide 1 receptor agonists (GLP-1 RAs), which aim to enhance glucose management and reduce the burden of dysmetabolism on certain organs. In addition to promoting weight loss by inducing satiety via central processes [i], GLP-1 RAs lower glycemia by regulating the release of insulin and glucagon in a glucose-dependent manner, with minimal risk of hypoglycemia, as per study results. According to clinical trials, the benefits extend even further, with studies showing improved lipid profile and blood pressure and protection against cardiovascular, renal, and liver damage [i]. Researchers revealed that nausea and vomiting are the most often reported adverse effects; however, they only affect a tiny percentage of people and are usually easily treated.

In terms of when it was introduced, Semaglutide is the most recent GLP-1 RA to be licensed to manage type 2 diabetes. 

Implications for Blood Pressure, Cholesterol, and Blood Glucose Control

Except for insulin, GLP-1 RAs have shown to be the most effective class of diabetic medicines in lowering levels of glycated hemoglobin (HbA1c), according to research. Semaglutide once weekly decreases HbA1c by 1.8%, compared to 1.2-1.4% for other long-acting GLP-1 RAs and 1.1% for oral Semaglutide, suggesting that this impact is larger for long-acting than short-acting formulations.

Influence on weight

Subjects diagnosed as “obese” should make a concerted effort to reduce their body weight. Weight reduction of at least 5 percent of body weight is associated with improved metabolic and cardiovascular health; this much is widely established. To lose weight, GLP-1 RAs make test subjects more in control of their eating and consume fewer calories.

According to research, among the GLP-1 RAs, Semaglutide is the most successful in helping test subjects shed extra pounds. 

Due to its positive impact on weight reduction in type 2 diabetes, Semaglutide has also been tested in non-diabetic obese subjects. After 68 weeks of treatment in the double-blind STEP 1 trial, which enrolled 1,961 obese subjects, those who received Semaglutide once weekly as an adjunct to lifestyle intervention lost, on average, 15.3 kilograms (14.9 percent) more weight than they had at baseline.

Result for metabolic liver disorders.

Metabolic liver diseases such as NAFLD and NASH are prevalent in subjects with type 2 diabetes and obesity [i]. Some illnesses have similar pathogenic pathways while being caused by different factors. Adipose tissue dysfunction, insulin resistance, hyperglycemia, impairment in the gut microbiome and cytokines profile, and the determination of a lipotoxic and metabolic liver burden, hepatocytes injury, fibrosis, and cirrhosis are all part of the complex, not fully understood interplay between “diabesity” and liver disease, particularly NAFLD and NASH [i].

The FDA has not yet validated pharmacological therapies for NAFLD/NASH. GLP-1 RAs have been proposed as a treatment for metabolic liver illnesses [13-15] because of their positive effects on metabolic parameters (blood glucose, insulin resistance, lipids) and weight reduction, according to research. Recently, 320 test subjects (with and without diabetes) participated in a randomized controlled study examining the effects of once-daily Semaglutide. Regardless of diabetes status, after 72 weeks, a greater proportion of participants in the Semaglutide treatment group than in the placebo group achieved NASH resolution. Still, no between-group differences were identified in liver fibrosis [i]. Fifty-two test subjects with NASH participated in the LEAN study, and those given Liraglutide once a day had a higher rate of NASH resolution than those given a placebo.

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