Should Rybelsus (Semaglutide) be discontinued with an A1C level of 5.4?

Discontinuing Rybelsus (Semaglutide) with an A1C of 5.4

Yes, Rybelsus should be discontinued when A1C reaches 5.4% due to the risk of overtreatment and potential hypoglycemia, particularly since this A1C level is well below the target range for most patients with diabetes. 1

Rationale for Discontinuation

• An A1C of 5.4% is below the typical target range of <7.0-7.5% for healthy adults with diabetes, and even below the more stringent target of <6.5% that might be appropriate for selected individuals 1
• At this low A1C level, the risk of treatment may outweigh the benefits, especially considering potential side effects of GLP-1 receptor agonists like Rybelsus 1
• A1C levels of 5.4% correspond to an average blood glucose of approximately 108 mg/dL, which is within the normal non-diabetic range 1

Evidence-Based Decision Making Framework

A1C Targets and Deintensification

• According to the 2024 American Diabetes Association Standards of Care, deintensification/deprescribing is indicated when A1C is appropriate or below target, especially with medications that carry risks 1
• The guidelines specifically state that "there is no need to deintensify therapy for an individual with an A1C between 6% and 7%" - implying that below 6% (as in this case with 5.4%), deintensification should be considered 1
• For patients with A1C below target, treatment simplification and deprescribing should be considered to avoid overtreatment 1

Risk-Benefit Assessment

• At an A1C of 5.4%, the incremental benefits of further glycemic control are minimal, while risks may increase 1
• Studies show that individuals with A1C levels in the range of 5.5-6.0% already have a 5-year cumulative incidence of diabetes that is 3-8 times higher than the general population, suggesting that 5.4% represents excellent control 1
• Even for patients with cardiovascular disease, there is no evidence that maintaining A1C below normal levels provides additional cardiovascular protection 1

Special Considerations

• If the patient has a history of severe hypoglycemia, advanced age, or multiple comorbidities, the case for discontinuation is even stronger 1
• For older adults, the 2024 Standards of Care specifically recommend treatment deintensification when A1C is appropriate or below target 1
• In patients with limited life expectancy or multiple comorbidities, A1C targets of <8% are considered appropriate, making 5.4% excessively low 1

Implementation Approach

• When discontinuing Rybelsus, monitor blood glucose levels more frequently in the first 2-4 weeks to ensure they remain in an acceptable range 1
• If the patient is on multiple glucose-lowering medications, consider discontinuing Rybelsus first while maintaining other treatments with lower hypoglycemia risk 1
• After discontinuation, continue lifestyle modifications including diet and exercise to maintain glycemic control 1
• Schedule follow-up A1C testing in 3 months to assess the impact of medication discontinuation 1

Potential Exceptions

• In rare cases where a patient has extremely high cardiovascular risk and has shown specific benefit from GLP-1 receptor agonist therapy beyond glycemic control (such as significant weight loss or blood pressure reduction), a risk-benefit discussion might be warranted before discontinuation 1
• If the patient has a history of significant glycemic variability not captured by A1C, consider using continuous glucose monitoring to ensure stable glucose levels before and after discontinuation 1

Remember that the primary goal of diabetes management is to reduce morbidity and mortality while maintaining quality of life, not simply achieving the lowest possible A1C level 1.