In a patient with type 2 diabetes on empagliflozin (Jardiance) 10 mg daily and HbA1c 8 %, can the dose be increased?

Can You Increase Jardiance from 10mg to 25mg with HbA1c of 8%?

Yes, you can and should increase empagliflozin (Jardiance) from 10mg to 25mg in this patient with HbA1c of 8%, as the FDA-approved dosing explicitly states that in patients tolerating the 10mg dose, it may be increased to 25mg for improved glycemic control. 1

FDA-Approved Dosing Strategy

• The FDA label for empagliflozin recommends starting at 10mg once daily, and in patients tolerating the medication, the dose may be increased to 25mg to achieve better glycemic outcomes 1
• This dose escalation is specifically supported for glycemic control improvement, which is clearly needed when HbA1c remains at 8% 1

Evidence Supporting Dose Escalation

Glycemic Efficacy by Dose

• Empagliflozin 25mg demonstrates superior HbA1c reduction compared to 10mg in multiple trials 2, 3
• In phase 2 trials, empagliflozin showed dose-dependent HbA1c reductions: 10mg reduced HbA1c by -0.5% while 25mg reduced it by -0.6% (both p<0.0001 vs placebo) 3
• A network meta-analysis found that when considering HbA1c, fasting plasma glucose, and adverse events together, 25mg performed best among all doses, with the ranking order for HbA1c reduction being 25mg > 50mg > 10mg > 5mg > 1mg 2

Cardiovascular Benefits Are Dose-Independent

• Importantly, the cardiovascular mortality benefits of empagliflozin (38% reduction in CV death) were demonstrated with both 10mg and 25mg doses pooled together in EMPA-REG OUTCOME 4, 5
• The American College of Cardiology notes that 10mg provides full cardioprotective benefit without need for titration for cardiovascular outcomes 5
• However, since this patient's primary issue is inadequate glycemic control (HbA1c 8%), the additional glucose-lowering efficacy of 25mg is clinically relevant 2

Safety Considerations for Dose Escalation

Adverse Event Profile

• The safety profile between 10mg and 25mg is comparable, with a dose-response trend showing only modest increases in total adverse events at higher doses 2
• In the EMPA-REG OUTCOME trial with over 7,000 patients, both 10mg and 25mg doses showed similar safety profiles over 3.1 years of follow-up 4
• Common adverse events (pollakiuria, thirst, genital infections) occur at similar rates between doses 3

Renal Function Check Required

• Before increasing the dose, verify that eGFR remains ≥45 mL/min/1.73 m², as empagliflozin should not be initiated or continued below this threshold for glycemic control 4, 1
• The FDA label explicitly states: "JARDIANCE should be discontinued if eGFR is persistently less than 45 mL/min/1.73 m²" 1
• For patients with stage 3b CKD (eGFR 30-44), the maximum dose is 10mg daily according to ADA/KDIGO consensus 4

Clinical Algorithm for Dose Escalation

Step 1: Verify Eligibility

• Confirm eGFR ≥45 mL/min/1.73 m² 4, 1
• Assess volume status and blood pressure (empagliflozin causes intravascular volume contraction) 1
• Review for contraindications: severe renal impairment, dialysis, or serious hypersensitivity 1

Step 2: Adjust Concomitant Medications

• If patient is on insulin or sulfonylureas, consider reducing their doses to mitigate hypoglycemia risk when intensifying SGLT2 inhibitor therapy 4
• The ADA/KDIGO consensus notes that adjustment of background therapies is generally not required when initiating an SGLT2i, but may be prudent in some patients 4

Step 3: Increase to 25mg

• Increase empagliflozin from 10mg to 25mg once daily 1
• Continue taking in the morning with or without food 1

Step 4: Monitor Response

• Reassess HbA1c in 12 weeks (25mg shows more significant benefit after long-term use ≥12 weeks) 2
• Monitor for volume depletion, especially in elderly patients or those on diuretics 1
• Watch for genital mycotic infections (occur in ~6% of SGLT2i users vs 1% placebo, higher risk in women) 4

Common Pitfalls to Avoid

Ketoacidosis Risk

• Educate the patient about euglycemic diabetic ketoacidosis, which can occur even with blood glucose <250 mg/dL 4, 1
• Instruct patient to discontinue empagliflozin during acute illness, surgery (3-4 days before), or periods of reduced oral intake 4, 6
• Maintain at least low-dose insulin if patient is on insulin therapy to mitigate DKA risk 4

Volume Depletion

• Empagliflozin causes intravascular volume contraction, particularly problematic in patients with renal impairment, low systolic BP, elderly patients, or those on diuretics 6, 1
• Correct volume status before dose escalation if indicated 1

Genital Infections

• Women have higher risk than men for mycotic genital infections 4
• Daily hygienic measures may lessen risk, and most infections are easily treated 4
• Rare but serious cases of Fournier gangrene have been reported 4

Expected Outcomes with Dose Escalation

• Expect additional HbA1c reduction of approximately 0.1-0.2% when escalating from 10mg to 25mg based on dose-response data 2, 3
• Weight loss of 2.6-3.8 kg can be expected regardless of dose 7
• Systolic and diastolic blood pressure reductions occur with both doses 7
• The cardiovascular and renal protective benefits established in EMPA-REG OUTCOME apply to both 10mg and 25mg doses 4, 5