Should we stop Synjardy (empagliflozin) in a patient with well-controlled Diabetes Mellitus?

Should Synjardy (Empagliflozin/Metformin) Be Stopped in a Patient with HbA1c 5.7%?

No, do not stop Synjardy in this patient with well-controlled diabetes (HbA1c 5.7%), hypertension, and hyperlipidemia, as empagliflozin provides critical cardiovascular and renal protection that extends far beyond glucose lowering, particularly in patients with multiple cardiovascular risk factors. 1

Why Continuation is Strongly Recommended

Cardiovascular Protection Independent of Glucose Control

• Empagliflozin reduces cardiovascular death by 38% and all-cause mortality by 32% in patients with type 2 diabetes and cardiovascular risk factors, benefits that occur independently of HbA1c levels 1, 2, 3
• The decision to continue empagliflozin should be made independently of baseline HbA1c or individualized HbA1c target, as cardiovascular and renal benefits persist even when glucose control is excellent 1
• In patients with established cardiovascular disease or multiple risk factors (like your patient with DM, HTN, and hyperlipidemia), empagliflozin reduces major adverse cardiovascular events (MACE) by 14% regardless of glycemic status 1, 4

Heart Failure Risk Reduction

• Empagliflozin reduces hospitalization for heart failure by 36%, a benefit that extends to patients without established heart failure at baseline 3, 5
• This patient's combination of diabetes, hypertension, and hyperlipidemia places them at very high risk for future heart failure, making empagliflozin particularly valuable 1, 6

Renal Protection Benefits

• SGLT2 inhibitors like empagliflozin prevent chronic kidney disease progression and reduce renal adverse events, benefits that are independent of glucose lowering 1, 2
• These renoprotective effects occur through mechanisms including reduced proximal tubular glucose reabsorption burden and improved renal hemodynamics 1

Clinical Decision Algorithm

Step 1: Assess Cardiovascular and Renal Risk Profile

• This patient has three major cardiovascular risk factors (diabetes, hypertension, hyperlipidemia), placing them in the very high-risk category for cardiovascular events 1
• Guidelines specifically recommend SGLT2 inhibitors with proven cardiovascular benefit in patients with type 2 diabetes and high cardiovascular risk to reduce MACE, hospitalization for heart failure, and cardiovascular death 1

Step 2: Evaluate Current Glycemic Status

• HbA1c of 5.7% indicates excellent glycemic control, which is below the prediabetes threshold and well below the diabetes diagnostic threshold 1
• However, the cardiovascular and renal benefits of empagliflozin are not restricted to patients with elevated HbA1c and should be considered independently of glucose levels 1

Step 3: Consider Hypoglycemia Risk

• At HbA1c 5.7%, there is theoretical concern for hypoglycemia, but empagliflozin carries a low inherent risk of hypoglycemia due to its insulin-independent mechanism of action 4, 3
• The FDA label confirms that hypoglycemia risk with empagliflozin is increased only when combined with insulin or insulin secretagogues (like sulfonylureas), not with metformin alone 7
• If hypoglycemia becomes a concern, consider reducing or stopping other glucose-lowering agents first, not the empagliflozin 1

Step 4: Monitor for Specific Safety Concerns

• Check renal function: empagliflozin is not recommended when eGFR is persistently <45 mL/min/1.73 m² and is contraindicated when eGFR <30 mL/min/1.73 m² 7
• Consider temporarily discontinuing empagliflozin only in settings of reduced oral intake (acute illness, fasting) or fluid losses (gastrointestinal illness, excessive heat exposure) to prevent acute kidney injury 7
• Monitor for genital mycotic infections and urinary tract infections, which are more common with SGLT2 inhibitors but generally straightforward to manage 7, 2

What About the Metformin Component?

• Metformin should be continued as it is first-line therapy with a low risk of hypoglycemia when used as monotherapy and provides cardiovascular benefits independent of glucose control 1
• Metformin has demonstrated reduction in risk of major adverse limb events (MALE) and MACE in patients with peripheral arterial disease, adding to its cardiovascular benefit profile 1
• At HbA1c 5.7%, metformin alone is unlikely to cause hypoglycemia and can be safely continued 1

Common Pitfalls to Avoid

• Do not stop empagliflozin solely based on low HbA1c: The cardiovascular and renal benefits are the primary indication in high-risk patients, not glucose lowering 1
• Do not assume all diabetes medications should be stopped when HbA1c is at target: Guidelines distinguish between medications that primarily lower glucose (which may be reduced) versus those with organ protection benefits (which should be continued) 1, 8
• Do not discontinue before travel without specific contraindications: The only travel-related concern would be if the patient anticipates prolonged periods of dehydration, reduced oral intake, or gastrointestinal illness, in which case temporary discontinuation may be considered 7

Monitoring Plan Going Forward

• Reassess HbA1c every 3 months to ensure it does not drop to levels that might indicate overtreatment with other agents 1
• Monitor renal function periodically, with more frequent monitoring if eGFR falls below 60 mL/min/1.73 m² 7
• Educate the patient about signs of volume depletion, urinary tract infections, and genital mycotic infections 7, 2
• If HbA1c remains consistently <5.5% and hypoglycemia becomes a concern, consider reducing other glucose-lowering agents (if any) rather than stopping empagliflozin 1, 8