What to do if hemoglobin A1C (HbA1c) is 6.2% on glipizide (Glipizide) and Jardiance (Empagliflozin) but need to switch Jardiance to Synjardy (Empagliflozin and Metformin) for financial reasons?

Switching from Jardiance to Synjardy with A1C 6.2%

You should proceed with switching from Jardiance (empagliflozin) to Synjardy (empagliflozin/metformin combination) without concern, as this change will likely improve glycemic control while maintaining cardiovascular and renal benefits, and you should strongly consider reducing or discontinuing glipizide given the excellent A1C of 6.2%. 1

Primary Recommendation: Switch to Synjardy and Deintensify Glipizide

The Switch is Safe and Beneficial

• Synjardy contains the same empagliflozin dose as Jardiance plus metformin, so you are simply adding metformin to the existing regimen, which is guideline-concordant therapy. 1
• Empagliflozin pharmacokinetics are identical with or without metformin coadministration, and empagliflozin has no clinically relevant effect on metformin pharmacokinetics, making this combination safe and predictable. 2
• The addition of metformin to empagliflozin provides cardiovascular mortality benefit, weight neutrality, and cost-effectiveness that complement the SGLT2 inhibitor. 3

Critical Action: Deintensify Glipizide

• With an A1C of 6.2%, you should strongly consider reducing the glipizide dose or discontinuing it entirely, as the American College of Physicians explicitly recommends deintensifying pharmacologic therapy when A1C levels fall below 6.5%. 1
• No trials demonstrate clinical outcome benefits at A1C levels below 6.5%, and treatment below this threshold is associated with substantial harms including hypoglycemia, increased mortality risk (as demonstrated by early termination of the ACCORD trial), and unnecessary treatment burden. 1
• Glipizide (a sulfonylurea) carries high hypoglycemia risk and causes weight gain, which contradicts the weight loss benefits of empagliflozin and should be the first medication reduced when A1C is below target. 1

Practical Implementation Algorithm

Step 1: Medication Adjustment

• Switch Jardiance to equivalent-dose Synjardy (e.g., if on Jardiance 10 mg, switch to Synjardy 10/500 mg or 10/1000 mg). 2
• Simultaneously reduce glipizide by 50% or discontinue it entirely, monitoring for any rise in glucose levels over the subsequent 2-4 weeks. 1
• If metformin causes gastrointestinal side effects, use extended-release formulations and titrate gradually to improve tolerability. 3

Step 2: Target A1C Range

• The appropriate A1C target for most adults with type 2 diabetes is 7-8%, balancing microvascular risk reduction against treatment harms. 1
• An A1C of 6.2% is below the recommended target and increases risk without providing additional benefit, particularly when achieved with a sulfonylurea that causes hypoglycemia. 1

Step 3: Monitoring Plan

• Reassess A1C in 3 months after the medication switch and glipizide reduction. 1, 3
• Monitor for hypoglycemia symptoms, particularly during the transition period if glipizide is continued at any dose. 1
• Check vitamin B12 levels periodically after starting metformin, as the Diabetes Prevention Program Outcomes Study suggests periodic testing. 1

Why This Approach is Optimal

Cardiovascular and Renal Protection Maintained

• Empagliflozin provides cardiovascular and renal benefits independent of A1C lowering, so maintaining the SGLT2 inhibitor component is essential regardless of current glycemic control. 1
• The cardiovascular benefits of SGLT2 inhibitors are not contingent upon A1C lowering and should be continued in patients with type 2 diabetes and cardiovascular disease independent of current A1C or A1C goal. 1

Financial Considerations Addressed

• Synjardy provides two medications in one pill, potentially reducing overall medication costs compared to separate prescriptions. 1
• Metformin is low-cost and generally well-tolerated, making it the most cost-effective glucose-lowering agent available. 1

Avoiding Common Pitfalls

• Do not maintain triple therapy (glipizide + empagliflozin + metformin) with an A1C of 6.2%, as this represents overtreatment and exposes the patient to unnecessary hypoglycemia risk. 1
• Do not delay deintensification due to concerns about glucose rising, as the target A1C range is 7-8%, providing a substantial buffer. 1
• Do not add additional glucose-lowering medications when A1C is already below target, as this increases treatment burden without clinical benefit. 1

Expected Outcomes

Glycemic Control

• The A1C may rise slightly (0.3-0.5%) after glipizide reduction, but this would still keep the patient well within the optimal target range of 7-8%. 1
• If A1C rises above 7%, metformin dose can be titrated upward within Synjardy formulations before considering reintroduction of other agents. 1

Safety Profile Improvement

• Hypoglycemia risk will decrease substantially with glipizide reduction or discontinuation. 1
• Weight may stabilize or decrease further with sulfonylurea removal, as glipizides cause weight gain while empagliflozin promotes weight loss. 1