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How do GLP-1 Agonists like Semaglutide help you to lose weight?

Updated: Dec 16, 2022

Semaglutide has been shown to produce weight loss in clinical studies, as well as other favorable metabolic changes. During weight management therapy with semaglutide, individuals experienced a substantially greater weight reduction than a placebo group on average. This weight can be maintained for up to two years when individuals continued semaglutide therapy after the weight-loss period ended. During these studies, favorable changes such as improved glucose levels and reduced body fat were also observed. With these promising outcomes, semaglutide appears to be an effective weight-loss agent with multiple supportive health benefits that could aid individuals across a range of body weight brackets.


Semaglutide is the first FDA-approved GLP-1 receptor agonist for obese adults who have a weight-related illness like type 2 diabetes, hypertension, and abnormal changes in lipid profile for use in concurrence with condensed calorie intake and improved physical activity.[1]


GLP-1 is an important, gut-derived, glucose homeostasis regulator that is released after the oral ingestion of carbohydrates or fats. In patients with Type 2 diabetes for example, GLP-1 concentrations are decreased in response to an oral glucose load. GLP-1 enhances insulin secretion; it increases glucose-dependent insulin synthesis and in vivo secretion of insulin from pancreatic beta cells in the presence of elevated glucose.


In addition to increases in insulin secretion and synthesis, GLP-1 suppresses glucagon secretion, slows gastric emptying, reduces food intake, and promotes beta-cell proliferation. Semaglutide reduces blood glucose through a mechanism where it stimulates insulin secretion and lowers glucagon secretion, both in a glucose-dependent manner. Therefore, when blood glucose is high, insulin secretion is stimulated and glucagon secretion is inhibited. The mechanism of blood glucose lowering also involves a minor delay in gastric emptying in the early postprandial phase. [2]


It basically helps you process glucose and makes you feel full sooner and longer thereby decreasing your intake as well as decreasing gastric emptying.

It can be used in addition to proper diet and exercise.

May cause nausea, vomiting, and diarrhea.

Newer GLP-1 agonist that is supposed to be more potent named tirzepatide.

Generally well tolerated with occasional nausea.

It does work and NEJM study shows once weekly subcutaneous administration of semaglutide plus lifestyle interventions was associated with sustained and clinically relevant reduction in body weight. [3]





Adverse reactions include: kidney failure, pancreatitis, gallbladder problems, nausea, vomiting, diarrhea, abdominal pain, and constipation. Hypoglycemia (dizziness, blurred vision, confusion, slurred speech, shakiness, sweating, jittery, fast heart rate)

In patients with heart disease can cause retinopathy or retinal damage.


Contraindications: NOT recommended taking if you have/had any of the following below.


Medullary thyroid carcinoma (MTC), multiple endocrine neoplasia syndrome type 2 (MEN 2), thyroid cancer, thyroid C-cell tumors

Semaglutide is contraindicated in patients with a personal or family history of certain types of thyroid cancer, specifically thyroid C-cell tumors such as medullary thyroid carcinoma (MTC), or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Semaglutide has been shown to cause dose-dependent and treatment duration-dependent malignant thyroid C-cell tumors at clinically relevant exposures in both genders of rats and mice. A statistically significant increase in cancer was observed in rats receiving semaglutide at all dose levels (greater than 2X human exposure). It is unknown whether semaglutide causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans.

Type 1 diabetes mellitus

Semaglutide should not be used for the treatment of type 1 diabetes mellitus.

Hypoglycemia

Pancreatitis

Cholelithiasis, gallbladder disease

Diabetic retinopathy

Renal failure, renal impairment

Depression, schizophrenia, suicidal ideation

Pregnancy

Reproductive risk

Semaglutide may be associated with reproductive risk and preconceptual planning is recommended; females of childbearing potential should discontinue semaglutide at least 2 months before a planned pregnancy due to the drug's long washout period.

Breast-feeding

Geriatric

Semaglutide has been studied in adults 65 years of age or older during clinical trials; safety and efficacy were not different in geriatric adults versus younger adults. In general, however, geriatric adults are especially at risk for hypoglycemic episodes. The specific reasons identified include intensive insulin therapy, decreased renal function, severe liver disease, alcohol ingestion, defective counter regulatory hormone release, missing meals/fasting, and gastroparesis. Because hypoglycemic events may be difficult to recognize in some elderly patients, antidiabetic agent regimens should be carefully managed to obviate an increased risk of severe hypoglycemia. [2]


If semaglutide or GLP-1 agonists sounds like a good option for you please contact us to setup a consultation.


References:

1. FDA Approves New Drug Treatment for Chronic Weight Management, First Since 2014 | FDA; 2021. Available from: FDA Article

2. PDR.net Semaglutide

3. NEJM

N Engl J Med 2021; 384:989-1002

DOI: 10.1056/NEJMoa2032183

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