Is a low hemoglobin A1c (HbA1c) level normal in an adult patient with type 2 diabetes taking tirzepatide (glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist)?

Low HbA1c on Tirzepatide: Expected and Normal

Yes, achieving a low HbA1c while on tirzepatide is entirely normal and expected, as this medication produces marked reductions in HbA1c ranging from 1.87% to 2.59% in clinical trials. 1

Understanding Tirzepatide's Potent Glucose-Lowering Effect

Tirzepatide is a first-in-class dual GIP/GLP-1 receptor agonist that demonstrates superior glycemic control compared to other diabetes medications:

• Tirzepatide produces HbA1c reductions of 1.87% to 2.59% across the SURPASS clinical trial program, which are among the most substantial reductions seen with any diabetes medication 1
• In head-to-head comparisons, tirzepatide was superior to semaglutide 1 mg for HbA1c reduction, demonstrating greater efficacy than even the most potent GLP-1 receptor agonists 1, 2
• The medication achieves these reductions with a low risk of hypoglycemia when not combined with insulin or sulfonylureas 1, 2

When Low HbA1c Becomes a Concern

While tirzepatide's efficacy is impressive, excessively low HbA1c levels warrant treatment adjustment:

• If HbA1c falls below 6.5%, clinicians should deintensify treatment by reducing dosage, removing a medication if on combination therapy, or discontinuing pharmacologic treatment 3
• No trials demonstrate clinical outcome benefits from targeting HbA1c below 6.5%, and the ACCORD trial targeting HbA1c <6.5% was discontinued early due to increased mortality and cardiovascular deaths 3
• The harms of targeting HbA1c below 6.5% include increased hypoglycemia risk, treatment burden, and costs without proven benefit 3

Appropriate HbA1c Targets on Tirzepatide

The target HbA1c should guide whether your current tirzepatide dose is appropriate:

• For most nonpregnant adults with type 2 diabetes, the recommended HbA1c target is 7% to 8% 3, 4
• More stringent targets of <6.5% may be reasonable only for selected patients with short diabetes duration, no cardiovascular disease, long life expectancy, and if achievable without adverse effects 3
• For older adults (≥80 years) or those with limited life expectancy (<10 years), avoid specific HbA1c targets and focus on minimizing hyperglycemic symptoms 3, 4

Clinical Action Steps

If your HbA1c is "low" on tirzepatide, determine the specific value and act accordingly:

• HbA1c 6.5% to 7%: This is generally appropriate for most patients; continue current therapy 3
• HbA1c <6.5%: Reduce tirzepatide dose (from 15 mg to 10 mg, or 10 mg to 5 mg) to avoid unnecessary treatment burden and potential harms 3
• HbA1c 7% to 8%: This is the optimal target range for most adults, particularly those with comorbidities or older age 3, 4

Important Caveats

• Tirzepatide's substantial weight loss effects (6.2 to 12.9 kg) may be a primary treatment goal independent of glycemic control, particularly in patients with obesity 3, 1
• The medication's gastrointestinal side effects (nausea, diarrhea, decreased appetite) are typically mild to moderate and transient 2, 5
• If HbA1c reduction brings you below target, this represents treatment success requiring dose adjustment, not treatment failure 3