From the Guidelines
GLP-1 receptor agonists, such as semaglutide and liraglutide, are recommended as second or third-line therapy for type 2 diabetes after metformin, and as primary therapy for obesity management in patients with BMI ≥30 kg/m² or ≥27 kg/m² with weight-related comorbidities, due to their ability to enhance glucose-dependent insulin secretion, suppress glucagon release, slow gastric emptying, and reduce appetite through central nervous system effects, as well as their cardiovascular protective benefits 1.
Key Recommendations
- For diabetes treatment, semaglutide (Ozempic) is typically started at 0.25 mg weekly for four weeks, then increased to 0.5 mg weekly, with a maximum of 2 mg weekly 1.
- For obesity treatment, higher doses are often used: liraglutide (Saxenda) up to 3 mg daily and semaglutide (Wegovy) up to 2.4 mg weekly 1.
- These medications should be avoided in patients with personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2, and used cautiously in those with pancreatitis history 1.
Adverse Effects
- Common side effects include nausea, vomiting, and diarrhea, which typically improve over time 1.
- Other potential adverse effects include hypoglycemia, injection site reactions, and gastrointestinal reflux 1.
- Acute pancreatitis is a rare but potential adverse effect, particularly with exenatide 1.
Cardiovascular Benefits
- Semaglutide and liraglutide have demonstrated reduced risk of major adverse cardiovascular events in clinical trials 1.
- The LEADER trial showed a benefit in cardiovascular outcomes with liraglutide, with a 13% reduction in the primary composite outcome of cardiovascular death, non-fatal myocardial infarction or stroke 1.
- The SUSTAIN 6 trial confirmed the cardiovascular benefit of semaglutide, with a 26% reduction in the primary outcome of cardiovascular death, non-fatal myocardial infarction or stroke 1.
From the FDA Drug Label
5 WARNINGS AND PRECAUTIONS 5.1 Risk of Thyroid C-Cell Tumors 5.2 Pancreatitis 5.3 Diabetic Retinopathy Complications 5.5 Hypoglycemia with Concomitant Use of Insulin Secretagogues or Insulin 5.6 Acute Kidney Injury 5.7 Hypersensitivity 6 ADVERSE REACTIONS 6.1 Clinical Trials Experience
The GLP-1 receptor agonists, such as semaglutide (Ozempic), have several warnings and precautions associated with their use, including:
- Risk of thyroid C-cell tumors
- Pancreatitis
- Diabetic retinopathy complications
- Hypoglycemia with concomitant use of insulin secretagogues or insulin
- Acute kidney injury
- Hypersensitivity The most likely adverse effects of GLP-1 medications include those listed in the clinical trials experience section of the drug label 2.
From the Research
GLP-1 Medications
GLP-1 receptor agonists, such as exenatide (Byetta), liraglutide (Victoza), and semaglutide (Ozempic), are used in the treatment of type 2 diabetes mellitus and obesity. These medications have been shown to be effective in reducing HbA1c levels, lowering postprandial blood glucose levels, and promoting weight loss 3, 4.
Mechanisms of Action
The mechanisms of action of GLP-1 receptor agonists include:
- Augmentation of hyperglycemia-induced insulin secretion
- Suppression of glucagon secretion at hyper- or euglycemia
- Deceleration of gastric emptying, preventing large post-meal glycemic increments
- Reduction in calorie intake and body weight 3, 4
Types of GLP-1 Receptor Agonists
There are two main types of GLP-1 receptor agonists:
- Short-acting agents (exenatide twice daily, lixisenatide) that primarily delay gastric emptying and lower postprandial glucose
- Long-acting agents (liraglutide, once-weekly exenatide, dulaglutide, albiglutide, and semaglutide) that affect both fasting glucose and postprandial glucose 5, 6
Adverse Effects
The most frequently observed adverse effects with GLP-1 receptor agonists are:
- Gastrointestinal disorders, particularly nausea, vomiting, and diarrhea 5, 4
- Injection-site reactions, which may be more common with certain formulations (exenatide twice daily and albiglutide) than others (liraglutide and dulaglutide) 5
Recommendations for Use
GLP-1 receptor agonists are recommended as the preferred first injectable glucose-lowering therapy for type 2 diabetes, even before insulin treatment, due to their effectiveness in reducing HbA1c levels and promoting weight loss, as well as their low risk of hypoglycemia 3. They may also be used in combination with basal insulin or other anti-diabetic drugs 4. The choice of GLP-1 receptor agonist should be individualized based on patient characteristics, preferences, and clinical profile 6.
Cardiovascular Benefits
GLP-1 receptor agonists have been shown to have cardiovascular benefits, including reducing the risk of acute myocardial infarction, stroke, and associated mortality, particularly in patients with pre-existing atherosclerotic vascular disease 3.
Weight Loss
GLP-1 receptor agonists can also promote weight loss, with a mean weight loss of approximately 2 to 3 kg, although there is significant heterogeneity in the magnitude of weight loss among individuals 7.