What are the different treatments for microdosing Glucagon-like peptide-1 (GLP-1) medications?

From the Guidelines

Microdosing GLP-1 medications, such as starting with 0.25mg of semaglutide (Ozempic) weekly, is a viable approach to minimize side effects while achieving therapeutic benefits, as supported by the most recent guidelines 1. When considering microdosing GLP-1 medications, it is essential to prioritize the patient's individual needs and health status. The goal of microdosing is to reduce common side effects like nausea, vomiting, and diarrhea, while still achieving some therapeutic benefit.

• Common microdosing approaches include starting with a low dose, such as 0.25mg of semaglutide (Ozempic) weekly or 3mg of liraglutide (Saxenda) daily, which is about 25-50% of the typical starting dose.
• A gradual titration schedule is crucial, increasing doses every 2-4 weeks as tolerated.
• Alternative microdosing methods include using the medication less frequently or diluting injectable solutions with sterile saline, although the latter is not officially recommended. The most recent guidelines suggest that GLP-1 receptor agonists, such as semaglutide, are effective for weight management and glycemic control, and should be prioritized when choosing glucose-lowering medications for people with type 2 diabetes and overweight or obesity 1.
• Semaglutide, in particular, has been shown to have a beneficial effect on weight and glycemic control, making it a preferred option for patients with type 2 diabetes and overweight or obesity.
• The guidelines also recommend considering the potential benefits and risks of weight management pharmacotherapy, and screening patients for malnutrition, especially those who have undergone metabolic surgery or are treated with weight management pharmacologic therapy 1. It is essential to discuss microdosing with a healthcare provider before implementation, as it may reduce therapeutic efficacy, particularly for weight management or glycemic control.
• The healthcare provider should evaluate the patient's individual needs and health status, and adjust the microdosing approach accordingly.
• Regular monitoring of the patient's response to microdosing is crucial, and adjustments should be made as needed to ensure optimal therapeutic benefits and minimize side effects.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Different Treatments for Microdosing GLP-1 Medications

• GLP-1 receptor agonists (GLP-1RAs) have emerged as key agents for weight management, with marked efficacy observed in randomized controlled trials 2.
• Real-world studies on GLP-1RA use in populations with obesity are increasingly available, demonstrating high discontinuation rates (20%-50%) within the first year and the use of much lower doses than those evaluated in clinical trials 2.
• The observed weight reduction in clinical practice overall tends to be lower than in randomized controlled trials; however, outcomes approach those seen in trials when focusing on highly adherent patients 2.
• GLP-1RAs have been shown to be effective therapeutic options at reducing A1C, with differences existing in terms of magnitude of effect on A1C and weight as well as frequency of adverse effects 3.
• Semaglutide and tirzepatide have been found to have a greater impact on weight loss, with mean weight loss of 9-16 kg and more than 50% of treated individuals achieving 10-15% or more weight loss 4, 5.
• Common adverse events associated with GLP-1RA use include gastrointestinal disturbances, hypotension, syncope, arthritic disorders, nephrolithiasis, interstitial nephritis, and drug-induced pancreatitis 6.
• GLP-1RAs have been found to be associated with a reduced risk of substance use and psychotic disorders, seizures, neurocognitive disorders, coagulation disorders, cardiometabolic disorders, infectious illnesses, and several respiratory conditions 6.

Comparison of Different GLP-1RAs

• Semaglutide has been found to have a greater mean weight loss compared to liraglutide and dulaglutide 5.
• Tirzepatide has been found to have a greater mean weight loss compared to semaglutide 5.
• Exenatide has been found to have a lower mean weight loss compared to semaglutide, liraglutide, and dulaglutide 5.
• The choice of GLP-1RA may depend on individual patient factors, such as the ability to stick to treatment plans, manage side effects, and afford the medications 2.