What is the best course of action for managing a 49-year-old male with diabetes, currently on Jardiance (Empagliflozin) 25 mg, with a Hemoglobin A1c (HbA1c) level of 7.8% and normal kidney function?

Management of Elevated HbA1c in a 49-Year-Old Male on Jardiance 25 mg

Add a GLP-1 receptor agonist with proven cardiovascular benefit (semaglutide, liraglutide, or dulaglutide) to the current Jardiance regimen immediately, as the HbA1c of 7.8% exceeds the target of <7.0% for this patient. 1, 2

Current Clinical Assessment

This patient demonstrates:

• Suboptimal glycemic control with HbA1c 7.8% on maximum-dose SGLT2 inhibitor monotherapy 1, 2
• Excellent renal function (eGFR 109 mL/min/1.73 m²) allowing full medication options 1
• Elevated hemoglobin/hematocrit (17.9 g/dL and 52.7%), which is a known effect of SGLT2 inhibitors due to hemoconcentration and is not concerning in this context 3, 4
• No contraindications to treatment intensification based on laboratory values 1

Treatment Intensification Algorithm

Step 1: Assess for Cardiovascular Disease and Heart Failure

• Screen for established atherosclerotic cardiovascular disease (prior MI, stroke, peripheral artery disease, or carotid stenosis >50%) as this fundamentally changes medication selection priorities 2
• Evaluate for heart failure history or symptoms, as the presence of heart failure with reduced ejection fraction would prioritize specific medication choices 2

Step 2: Select Second Agent Based on Comorbidity Status

If cardiovascular disease is present:

• First choice: GLP-1 receptor agonist with proven cardiovascular benefit (semaglutide, liraglutide, or dulaglutide) to reduce cardiovascular mortality 1, 2
• Alternative: Continue Jardiance and add the GLP-1 RA, as both classes provide complementary cardiovascular and renal protection 1, 2

If heart failure is present:

• Continue Jardiance as the SGLT2 inhibitor class reduces heart failure hospitalizations 1, 2
• Add GLP-1 receptor agonist for additional glycemic control and cardiovascular benefit 2

If no cardiovascular disease or heart failure:

• Add GLP-1 receptor agonist as the preferred second agent due to superior efficacy (expected HbA1c reduction 1.0-1.5%), weight loss benefit, and lack of hypoglycemia risk 1, 2, 5
• Alternative options include DPP-4 inhibitors, basal insulin, or sulfonylureas, though these are less preferred 1

Step 3: Specific GLP-1 Receptor Agonist Selection

Semaglutide provides the greatest HbA1c reduction (1.0-1.5%) and significant weight loss with proven cardiovascular benefit 2

Dulaglutide offers comparable efficacy with weekly dosing and proven cardiovascular benefit 2

Liraglutide is an alternative daily injection with proven cardiovascular mortality reduction 1, 2

Expected Outcomes

• HbA1c reduction of 1.0-1.5% with GLP-1 receptor agonist addition, bringing HbA1c from 7.8% to approximately 6.3-6.8% 2, 5
• Weight loss of 2-5 kg typically occurs with GLP-1 receptor agonists 2
• No increased hypoglycemia risk as neither SGLT2 inhibitors nor GLP-1 receptor agonists cause hypoglycemia when used without insulin or sulfonylureas 1, 4

Why Not Other Options?

Sulfonylureas are not recommended as second-line therapy due to hypoglycemia risk, weight gain, and lack of cardiovascular benefit 1, 2

Basal insulin is reserved for patients who fail dual or triple oral therapy, or when GLP-1 receptor agonists are contraindicated or not tolerated 1

DPP-4 inhibitors are less effective than GLP-1 receptor agonists (HbA1c reduction only 0.7-1.0%) and lack cardiovascular mortality benefit 1, 2

Monitoring Plan

• Recheck HbA1c in 3 months to evaluate treatment response 2
• Monitor for GI side effects (nausea, vomiting, diarrhea) which are common with GLP-1 receptor agonist initiation but typically resolve within 4-8 weeks 2
• Continue monitoring for genital mycotic infections associated with SGLT2 inhibitors 1, 4
• Assess volume status at follow-up, though hypotension risk is low with normal renal function 1

Critical Caveats

Do not delay treatment intensification beyond 3 months of suboptimal control, as the American Diabetes Association guidelines emphasize prompt escalation when HbA1c exceeds target 1

Do not target HbA1c <6.5% as this increases hypoglycemia risk without additional cardiovascular benefits and may require treatment deintensification 2

Continue Jardiance rather than switching agents, as SGLT2 inhibitors provide kidney and cardiovascular protection independent of glucose-lowering effects, and this benefit is preserved even at lower eGFR levels 1, 4

Counsel on euglycemic ketoacidosis risk with SGLT2 inhibitors during acute illness, though absolute risk is low; advise temporarily discontinuing Jardiance during periods of acute stress or illness 1