Is gliclazide (BID, twice a day) 30 mg and empagliflozin (OD, once a day) 25 mg effective in controlling blood sugar levels in type 2 diabetes?

Gliclazide 30 mg BID Plus Empagliflozin 25 mg OD for Type 2 Diabetes Control

This combination can effectively control blood sugar in type 2 diabetes, with empagliflozin 25 mg providing approximately 0.5-1.0% HbA1c reduction when added to existing sulfonylurea therapy, though the regimen requires careful monitoring for hypoglycemia and consideration of cardiovascular/renal status. 1, 2

Glycemic Efficacy of the Combination

Expected HbA1c Reduction

• Empagliflozin 25 mg added to metformin plus gliclazide reduces HbA1c by approximately 0.8-1.0% in real-world studies 2
• The glucose-lowering effect is dose-independent between 10 mg and 25 mg empagliflozin when combined with sulfonylureas, with both doses showing statistically significant HbA1c reductions (p<0.001) 2
• Each non-insulin agent class typically lowers HbA1c by 0.7-1.0% when added to existing therapy 1

Clinical Trial Evidence

• A 12-week real-world study of 60 patients receiving metformin plus gliclazide showed significant HbA1c reduction when empagliflozin was added, regardless of 10 mg or 25 mg dosing 2
• The combination of gliclazide with SGLT2 inhibitors has demonstrated sustained efficacy over extended treatment periods 3

Critical Safety Considerations

Hypoglycemia Risk Management

• The risk of hypoglycemia increases significantly when empagliflozin is combined with sulfonylureas like gliclazide 1, 4
• When adding empagliflozin to patients already on sulfonylureas, reduce the sulfonylurea dose or consider weaning/stopping it to prevent hypoglycemia 1
• Gliclazide 30 mg BID (total 60 mg daily) is a moderate dose that may require reduction when empagliflozin is initiated 2
• Confirmed hypoglycemic events occur in approximately 2% of patients on empagliflozin combinations versus 24% with sulfonylurea-intensive regimens 3

Renal Function Monitoring

• Empagliflozin's glucose-lowering efficacy decreases substantially with declining renal function: -0.6% HbA1c reduction for eGFR 60-90 mL/min/1.73 m², -0.5% for eGFR 45-60, and only -0.2% for eGFR 30-45 1
• Do not initiate empagliflozin for glycemic control if eGFR <45 mL/min/1.73 m², though cardiovascular/renal benefits persist down to eGFR ≥25 mL/min/1.73 m² 5, 1
• The drug should be discontinued if eGFR falls below 45 mL/min/1.73 m² during treatment for glycemic purposes 4

Additional Therapeutic Benefits Beyond Glycemia

Cardiovascular Protection

• Empagliflozin is specifically recommended in patients with type 2 diabetes and established cardiovascular disease or high CV risk to reduce cardiovascular events and mortality 5
• The drug reduces cardiovascular death by 38% (HR 0.62,95% CI 0.49-0.77) and heart failure hospitalization by 35% (HR 0.65,95% CI 0.50-0.85) in high-risk patients 5
• These cardiovascular benefits are independent of glucose-lowering effects and emerge over months to years of continuous therapy 1, 6

Weight and Blood Pressure Effects

• Patients lose 2.6-3.8 kg of body weight with empagliflozin addition, with greater weight loss at 25 mg versus 10 mg dosing 2
• Significant reductions in both systolic and diastolic blood pressure occur (p<0.0001) 2
• The energy expenditure from glycosuria amounts to 200-400 kcal/day 4

Renal Protection

• SGLT2 inhibitors including empagliflozin are recommended to reduce progression of diabetic kidney disease 5
• Empagliflozin demonstrates renal protective effects with reduced progression of kidney disease 7

Practical Implementation Algorithm

Patient Selection Criteria

1. Prioritize this combination for patients with:

   • Type 2 diabetes inadequately controlled on sulfonylurea monotherapy or dual therapy 2
   • Established cardiovascular disease or very high/high CV risk 5
   • eGFR ≥45 mL/min/1.73 m² for glycemic control purposes 5, 1
   • Need for weight reduction and blood pressure lowering 2

2. Exercise caution in:

   • Elderly or fragile patients due to potential dehydration/hypotension risk 4
   • Patients with recurrent genital or urinary tract infections 2
   • Those with eGFR 30-45 mL/min/1.73 m² (cardiovascular benefits persist but glycemic efficacy is minimal) 1

Dosing Strategy

• Start empagliflozin at 10 mg once daily for cardiovascular risk reduction; no titration beyond 10 mg is necessary for this indication 5, 1
• The 25 mg dose may be used for enhanced glycemic control in patients with eGFR ≥60 mL/min/1.73 m², though glycemic benefit over 10 mg is modest 5, 1
• Consider reducing gliclazide dose by approximately 20% when initiating empagliflozin to minimize hypoglycemia risk 1

Monitoring Requirements

• Assess HbA1c at 12 weeks (3 months) to evaluate glycemic response and determine if therapy intensification is needed 6
• Monitor renal function and blood pressure routinely 7
• Check for genital and urinary tract infections, which occur more frequently in women 4, 2
• Educate patients on sick day management: temporarily stop empagliflozin during acute illness with significant fluid losses, inability to maintain oral intake, volume depletion signs, or moderate/high ketones 7

Important Caveats

Infection Risk

• Higher incidence of genital infections occurs with empagliflozin, especially in women, though these are typically non-severe 4
• No statistically significant increase in urinary tract infections was found in the 12-week study, though numerical increases occurred 2

Lipid Profile

• Empagliflozin demonstrates a neutral effect on lipid metabolism with no significant changes in lipid parameters 2
• This contrasts with theoretical advantages of gliclazide over glibenclamide regarding lipid and hemorheologic profiles 8

Treatment Durability

• Empagliflozin's efficacy does not decrease over time as it is not dependent on endogenous insulin production 4
• The combination shows sustained glucose-lowering effects over extended treatment periods 3

Alternative Considerations

• If HbA1c remains above goal after 3 months, consider adding a GLP-1 receptor agonist, which has greater glycemic potency than SGLT2 inhibitors 7, 1
• Many patients require triple therapy (metformin + GLP-1 RA + SGLT2 inhibitor) to achieve glycemic goals 1