From the Guidelines
Orfoglipron, as a GLP-1 receptor agonist, has the potential to play a significant role in managing type 2 diabetes by improving glycemic control, promoting weight loss, and possibly reducing the risk of major adverse cardiovascular events. The medication works by mimicking the action of the naturally occurring hormone GLP-1, which stimulates insulin secretion in response to elevated blood glucose levels, suppresses glucagon release, slows gastric emptying, and increases satiety 1. Unlike injectable GLP-1 agonists such as semaglutide or liraglutide, Orfoglipron is being developed as an oral medication, which may improve patient adherence. Key benefits of GLP-1 receptor agonists, as seen in studies with other agents in this class like liraglutide, include a reduction in the risk of major adverse cardiac events (MACE) and a potential slowing of eGFR decline in patients with chronic kidney disease (CKD) 1. Common side effects of GLP-1 receptor agonists may include gastrointestinal symptoms such as nausea, vomiting, and diarrhea, which often diminish over time 1. Given the potential benefits and the side effect profile, the use of Orfoglipron, once approved, could be considered as part of a comprehensive diabetes management plan that includes diet and exercise, particularly for patients who may benefit from the oral route of administration and have a high risk of cardiovascular events or CKD. It's crucial to note that as of the last update, Orfoglipron is still in clinical development and not yet approved by regulatory agencies for widespread use in treating type 2 diabetes. However, based on the evidence from similar GLP-1 receptor agonists, Orfoglipron is likely to offer significant benefits in terms of glycemic control and cardiovascular risk reduction, making it a promising therapeutic option for the management of type 2 diabetes 1.
From the FDA Drug Label
The FDA drug label does not answer the question.
From the Research
Role of Orfoglipron in Managing Type 2 Diabetes
- Orfoglipron, a novel oral, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated efficacy in improving glycemic control and body weight reduction in patients with type 2 diabetes 2, 3, 4.
- The primary efficacy outcome of orfoglipron treatment was a significant reduction in HbA1c levels, with a mean change of up to -2.10% (-1.67% placebo-adjusted) at week 26, compared to -0.43% with placebo and -1.10% with dulaglutide 3.
- Orfoglipron treatment also resulted in significant reductions in body weight, with a mean change of up to -10.1 kg (7.9 kg placebo-adjusted) at week 26, compared to -2.2 kg with placebo and -3.9 kg with dulaglutide 3.
- The incidence of treatment-emergent adverse events with orfoglipron was similar to other GLP-1 receptor agonists, with the majority being gastrointestinal events of mild to moderate severity 3, 4.
Cardiovascular Benefits
- Orfoglipron treatment was associated with beneficial changes in cardiovascular risk markers, including significant decreases in blood pressure, low-density lipoprotein (LDL) cholesterol, triglycerides, Apolipoprotein B (ApoB), and high-sensitivity C-reactive protein (hsCRP) 2.
- These findings suggest that orfoglipron may have a positive impact on cardiovascular health, although further studies are needed to confirm its long-term cardiovascular benefits.
Comparison to Other GLP-1 Receptor Agonists
- Orfoglipron has a similar mechanism of action to other GLP-1 receptor agonists, including augmentation of hyperglycemia-induced insulin secretion, suppression of glucagon secretion, and deceleration of gastric emptying 5.
- However, orfoglipron is an oral, non-peptide GLP-1 receptor agonist, which may provide a more convenient and less burdensome treatment option for patients with type 2 diabetes, compared to injectable GLP-1 receptor agonists 3, 4.