Should This Patient Continue Metformin?

No, metformin should be discontinued in this patient with prediabetes (HbA1c 5.3%) who is being treated with tirzepatide for weight loss. 1

Rationale for Discontinuation

The HbA1c of 5.3% falls within the normal range (below 5.7%), indicating this patient does not have diabetes and likely has prediabetes at most. 1
Metformin is not indicated for prediabetes treatment in routine clinical practice, as approximately two-thirds of people with prediabetes never develop diabetes, and one-third return to normal glucose regulation without pharmacologic intervention. 1
People with prediabetes are not at risk for microvascular complications of diabetes, which is the primary reason to treat hyperglycemia pharmacologically. 1

Tirzepatide has demonstrated unprecedented glycemic control, with 23-62% of patients achieving HbA1c <5.7% (normoglycemia) in clinical trials, making additional glucose-lowering medication unnecessary. 2
In the SURPASS trials, tirzepatide reduced HbA1c by 1.24-2.58%, far exceeding metformin's typical 0.7-1.5% reduction. 3, 2
The patient's current HbA1c of 5.3% indicates excellent glycemic control is already achieved with tirzepatide alone. 2

There is no evidence that maintaining metformin in a patient with normal glucose levels (HbA1c 5.3%) provides cardiovascular or mortality benefits, as these benefits were demonstrated in patients with established diabetes. 3
Continuing metformin exposes the patient to unnecessary gastrointestinal side effects, potential vitamin B12 deficiency with long-term use, and medication burden without clear benefit. 3
The only theoretical reason to use metformin in prediabetes would be diabetes prevention, but this patient should simply be monitored and metformin reintroduced only if diabetes is actually diagnosed (HbA1c ≥6.5%). 1

If HbA1c rises to ≥6.5% on repeat testing, confirming type 2 diabetes diagnosis, metformin should be initiated as first-line therapy alongside tirzepatide. 3
Guidelines recommend metformin as foundational therapy for type 2 diabetes regardless of baseline HbA1c, with other agents added based on comorbidities. 3

In patients with established atherosclerotic cardiovascular disease (ASCVD) and type 2 diabetes, metformin should be continued as background therapy when adding GLP-1 receptor agonists, though most cardiovascular outcome trial data included patients already on metformin. 3
However, this recommendation applies to patients with diabetes, not prediabetes. 3

Check HbA1c every 6-12 months to monitor for progression to diabetes (HbA1c ≥6.5%). 3
If HbA1c rises to 6.0-6.4% (high-risk prediabetes range), increase monitoring frequency to every 3-6 months. 1

Tirzepatide should be continued for its primary indication of weight loss and metabolic improvement in this patient. 2
Monitor for gastrointestinal side effects (nausea, vomiting, diarrhea) which are the most common adverse events with tirzepatide. 2, 4

Immediately start metformin if HbA1c reaches ≥6.5% on repeat testing, confirming diabetes diagnosis. 1
At that point, metformin would be added to tirzepatide as combination therapy for type 2 diabetes management. 3

Do not continue metformin "just in case" for diabetes prevention when the patient has normal glucose levels and is already on effective therapy—this exposes them to unnecessary medication burden and side effects without proven benefit in this specific clinical scenario. 1
Do not assume tirzepatide alone is insufficient simply because guidelines emphasize metformin as first-line therapy for diabetes—those guidelines apply to patients with established diabetes, not prediabetes with normal HbA1c. 3, 1
Do not delay discontinuation waiting for "more data"—the patient's HbA1c of 5.3% clearly indicates they do not currently have diabetes and metformin is not indicated for prediabetes treatment outside of high-risk populations in research settings. 1