Type 2 diabetes mellitus (T2DM) is a metabolic disorder affecting millions globally. Effective management of T2DM involves controlling glycated hemoglobin (HbA1c) levels, body weight, blood pressure, and lipids. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a crucial class of medications for T2DM management, offering benefits beyond glycemic control, including weight loss and cardiovascular risk reduction. This article provides a detailed comparison of two prominent GLP-1 RAs: dulaglutide and semaglutide, focusing on their efficacy in weight loss and glycemic control.
Introduction to GLP-1 Receptor Agonists
GLP-1 RAs mimic the action of the naturally occurring GLP-1 hormone in the body. These drugs stimulate insulin secretion and reduce glucagon secretion in a glucose-dependent manner, lowering the risk of hypoglycemia. Additionally, they delay gastric emptying, which can lead to lower postprandial blood glucose levels and contribute to weight loss.
The class of medications known as GLP1 drugs has been in the news lately. GLP1s, or glucagon-like peptide-1 receptor agonists, are also called GLP-1 receptor agonists, incretin mimetics, or GLP-1 analogs.
Dulaglutide and Semaglutide: An Overview
Dulaglutide (Trulicity®) and semaglutide (Ozempic®, Rybelsus®, Wegovy®) are both GLP-1 RAs approved for treating T2DM. While they share a mechanism of action, there are important differences in their structure, administration, and clinical effects.
- Dulaglutide: Approved earlier than some other GLP-1 RAs, dulaglutide is available only as a once-weekly subcutaneous injection.
- Semaglutide: Available in both once-weekly subcutaneous injection (Ozempic® and Wegovy®) and oral daily tablet (Rybelsus®) formulations. In 2021, semaglutide (Wegovy®) gained FDA approval for chronic weight management in obese and overweight patients with at least one weight-related condition.
Dulaglutide has 90% similar genetic makeup to the human GLP-1, while semaglutide has 94%.
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Dosage and Administration
Both dulaglutide and semaglutide require initial starting doses with gradual increases to reach the recommended maintenance dose.
- Dulaglutide: Administered as a once-weekly subcutaneous injection. The starting dose is 0.75 mg, which may be increased to 1.5 mg weekly. Some studies have used a maximum dose of 4.5 mg weekly.
- Semaglutide: Available in both injectable and oral forms. The injectable form (Ozempic®) starts at 0.25 mg once weekly for four weeks, then increases to 0.5 mg weekly. If additional glycemic control is needed, the dose can be further increased to 1 mg or 2 mg weekly. The oral form (Rybelsus®) also follows a similar titration schedule.
Efficacy in Glycemic Control
Clinical trials have demonstrated the efficacy of both dulaglutide and semaglutide in improving glycemic control in patients with T2DM.
A systematic review and meta-analysis aimed to evaluate the effectiveness of semaglutide and dulaglutide for glycemic control and weight loss in patients with type 2 diabetes mellitus (T2DM) showed no statistically significant difference in glycemic control achievement between the two medications in patients with T2DM.
Comparison trial SUSTAIN 7 investigated semaglutide vs dulaglutide. Semaglutide had a higher HbA1c reduction in comparison to dulaglutide (-1.4 vs -1.1 respectively, p=0.002) with comparing dulaglutide 0.75mg and semaglutide 0.5mg. A higher percentage of patients were able to achieve hba1c <7% at week 40 with semaglutide 0.5mg (65% vs 51%, p=<0.0001).
Impact on Weight Loss
One of the significant benefits of GLP-1 RAs is their ability to promote weight loss. Semaglutide has generally shown superior efficacy in reducing body weight compared to dulaglutide.
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Semaglutide demonstrated higher efficacy in inducing weight loss; however, sensitivity analysis indicated that the weight loss efficacy results should be interpreted cautiously.
Semaglutide 1.0 mg significantly reduced body weight versus dulaglutide 3.0 and 4.5 mg with an ETD of −2.65 kg (95% CI −3.57, −1.73) and −1.95 kg (95% CI −2.87, −1.03), respectively. This indirect comparison showed significantly greater reductions in HbA1c with semaglutide 1.0 mg versus dulaglutide 3.0 mg and comparable HbA1c reductions versus dulaglutide 4.5 mg. Semaglutide 1.0 mg significantly reduced body weight versus both dulaglutide 3.0 and 4.5 mg.
Cardiovascular Outcomes
GLP-1 RAs have demonstrated cardiovascular benefits in several clinical trials. A real-world study using the TriNetX platform compared the cardiovascular outcomes of semaglutide and dulaglutide. The 3-year risks of all-cause death, acute myocardial infarction, stroke, and acute heart failure were significantly lower in patients with type 2 diabetes who received semaglutide than in those who received dulaglutide.
Safety and Side Effects
The side effects of dulaglutide and semaglutide are similar. The most common side effects include nausea, diarrhea, vomiting, and abdominal pain. Both drugs carry a boxed warning for the risk of thyroid C-cell tumors and should be avoided in patients with a personal or family history of certain thyroid cancers. Additional warnings and precautions include pancreatitis, gallbladder disease, kidney damage, increased heart rate, low blood glucose levels, and eye disorders in type 2 diabetics.
Head-to-Head Clinical Trials and Meta-Analyses
Several head-to-head trials and meta-analyses have compared the efficacy and safety of semaglutide and dulaglutide.
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In a clinical trial, semaglutide showed superiority over dulaglutide to improve glucose control and weight loss greater than 5% in type 2 diabetic adult patients.
Indirect Comparisons
Pratley RE, Catarig A‐M, Lingvay I, et al. conducted an indirect treatment comparison of the efficacy of semaglutide 1.0 mg versus dulaglutide 3.0 and 4.5 mg. Semaglutide 1.0 mg significantly reduced HbA1c versus dulaglutide 3.0 mg, with an estimated treatment difference (ETD) of −0.24%‐points (95% confidence interval [CI] −0.43, −0.05), with comparable reductions in HbA1c versus dulaglutide 4.5 mg with an ETD of −0.07%‐points (95% CI −0.26, 0.12). Semaglutide 1.0 mg significantly reduced body weight versus dulaglutide 3.0 and 4.5 mg with an ETD of −2.65 kg (95% CI −3.57, −1.73) and −1.95 kg (95% CI −2.87, −1.03), respectively.
Considerations for Clinical Practice
Choosing between dulaglutide and semaglutide depends on several factors, including:
- Efficacy Goals: If weight loss is a primary goal, semaglutide may be preferred due to its superior weight reduction effects.
- Patient Preference: Some patients may prefer the oral formulation of semaglutide (Rybelsus®), while others may find the once-weekly injection of dulaglutide more convenient.
- Side Effect Profile: Patients who are more sensitive to gastrointestinal side effects may tolerate dulaglutide better.
- Cost and Insurance Coverage: The cost and insurance coverage for each medication should be considered, as they can vary.
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