What is the effect of semaglutide (GLP-1 receptor agonist)?

From the Guidelines

Semaglutide is recommended for patients with type 2 diabetes due to its proven efficacy in reducing the risk of major adverse cardiovascular events, as demonstrated in the SUSTAIN-6 trial 1.

Key Points

• Semaglutide is a once-weekly GLP-1 receptor agonist approved by the FDA for the treatment of type 2 diabetes.
• The SUSTAIN-6 trial showed that semaglutide reduced the risk of cardiovascular death, nonfatal MI, or nonfatal stroke by 26% compared to placebo 1.
• The primary outcome of cardiovascular death, nonfatal MI, or nonfatal stroke occurred in 108 patients (6.6%) in the semaglutide group vs. 146 patients (8.9%) in the placebo group (HR 0.74; 95% CI 0.58–0.95; P < 0.001) 1.
• More patients discontinued treatment in the semaglutide group due to adverse events, mainly gastrointestinal 1.
• The cardiovascular effects of the oral formulation of semaglutide compared to placebo have been assessed in Peptide Innovation for Early Diabetes Treatment (PIONEER) 6, a preapproval trial designed to rule out an unacceptable increase in cardiovascular risk 1.

Dosage and Administration

• The typical starting dose of semaglutide is 0.25 mg injected subcutaneously once weekly, gradually increasing to a maintenance dose of 1-2.4 mg weekly depending on the indication.
• Patients should store the medication in the refrigerator before first use and inject it on the same day each week.

Efficacy and Safety

• Semaglutide has shown significant effectiveness for both blood sugar control and weight loss, with many patients losing 10-15% of their body weight when used for obesity treatment alongside lifestyle changes.
• Common side effects include nausea, vomiting, diarrhea, and constipation, which often improve over time.

Recent Guidelines

• The 2024 standards of care in diabetes recommend using GLP-1 receptor agonists, such as semaglutide, to reduce the risk of major adverse cardiovascular events in patients with type 2 diabetes and established ASCVD, multiple ASCVD risk factors, or diabetic kidney disease 1.

From the FDA Drug Label

6%) patients were 75 years of age and over. No overall differences in safety or efficacy were detected between these patients and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

1. 6 Renal Impairment No dose adjustment of OZEMPIC is recommended for patients with renal impairment. In subjects with renal impairment including end-stage renal disease (ESRD), no clinically relevant change in semaglutide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12.3)].

2. 7 Hepatic Impairment No dose adjustment of OZEMPIC is recommended for patients with hepatic impairment. In a study in subjects with different degrees of hepatic impairment, no clinically relevant change in semaglutide pharmacokinetics (PK) was observed [see Clinical Pharmacology (12. 3)].

3. 1 Mechanism of Action Semaglutide is a GLP-1 analogue with 94% sequence homology to human GLP-1. Semaglutide acts as a GLP-1 receptor agonist that selectively binds to and activates the GLP-1 receptor, the target for native GLP-1.

4. 2 Pharmacodynamics Semaglutide lowers fasting and postprandial blood glucose and reduces body weight.

5. 3 Pharmacokinetics Absorption Absolute bioavailability of semaglutide is 89%. Maximum concentration of semaglutide is reached 1 to 3 days post dose.

Semaglutide is a GLP-1 receptor agonist that lowers blood glucose and reduces body weight. It has a long half-life of approximately 1 week and is extensively bound to plasma albumin.

• No dose adjustment is recommended for patients with renal impairment or hepatic impairment.
• Semaglutide has a mechanism of action that involves stimulating insulin secretion and lowering glucagon secretion in a glucose-dependent manner.
• The pharmacokinetics of semaglutide are characterized by an absolute bioavailability of 89% and a maximum concentration reached 1 to 3 days post dose 2.

From the Research

Semaglutide Overview

• Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist used for the management of type 2 diabetes 3, 4.
• It is available in both subcutaneous and oral dosage forms, with the oral form being the first approved oral GLP-1 receptor agonist 4.

Efficacy and Safety

• Oral semaglutide has been shown to reduce mean HbA1c by approximately 1.1-1.5% and body weight by up to 5 kg in clinical trials 3.
• It has also been demonstrated to be safe in adults and elderly patients with renal or hepatic disorders, with no requirement for dose modification 4, 5.
• The most common side effects of semaglutide are gastrointestinal, mainly mild-to-moderate and transient nausea 3, 5.

Cardiovascular Benefits

• Semaglutide has been proven to reduce various cardiovascular risk factors in patients with established cardiovascular disorders 4, 6.
• It has been shown to decrease major adverse cardiovascular events (MACE) and progression of chronic kidney disease (CKD) 6, 7.
• Oral semaglutide has also been found to improve body weight, blood pressure, HbA1c, LDL-C, non-HDL-C, and urinary albumin to creatinine ratio (UACR) in type 2 diabetic patients 6.

Cost-Effectiveness

• Semaglutide has been found to be cost-effective compared to other GLP-1 receptor agonists or placebo in patients with type 2 diabetes mellitus (T2DM) 7.
• It has been associated with a lower number of MACE and is more cost-effective, with a significant reduction in HbA1c levels and body weight in routine clinical practice 7.