Insulin Glargine Dosing and Adjunct Therapy for HbA1c 8.9%
Insulin Glargine Dosing Regimen
Insulin glargine should be dosed once daily (not split between morning and evening), starting at 10 units daily or 0.1-0.2 units/kg/day, with titration of 2 units every 3 days until fasting blood glucose reaches target. 1
- Glargine is a basal insulin designed for once-daily administration, typically given at bedtime or in the morning at the same time each day 2
- The initial dose should not exceed approximately 0.5 units/kg/day to avoid overbasalization 1
- Titrate upward by 2 units every 3 days based on fasting glucose readings, targeting fasting plasma glucose <130 mg/dL 3
- If hypoglycemia occurs, reduce the dose by 10-20% 1
Important caveat: Glargine is never split into morning and evening doses—this is a common error. If twice-daily basal coverage is needed, NPH insulin would be the appropriate choice, not glargine 2
Dapagliflozin and Linagliptin as Adjunct Therapy
Yes, the combination of dapagliflozin and linagliptin is an excellent adjunct treatment option for HbA1c 8.9%, providing superior glycemic control compared to either agent alone while maintaining a favorable safety profile. 4, 5
Evidence Supporting This Combination
- For HbA1c 8.9%, combination therapy with dapagliflozin plus linagliptin added to metformin reduced HbA1c by approximately 1.6-1.7% from baseline, significantly more than either agent alone 5, 6
- In patients with baseline HbA1c 7.90-8.02%, the combination reduced HbA1c by 1.08-1.19% versus 0.62-0.70% with individual components 4
- This combination addresses multiple pathophysiologic defects: linagliptin improves beta-cell function and reduces glucagon, while dapagliflozin reduces glucotoxicity through glucosuria 7
- The combination is particularly effective at HbA1c levels below 9.0%, where it produces additive effects 7
Safety and Tolerability Profile
- The combination has a low risk of hypoglycemia, making it safer than sulfonylureas or intensive insulin regimens 4, 7
- Adverse events are mild and similar to monotherapy rates (7.2% experiencing any adverse events, all mild and resolved) 5
- The combination provides weight loss benefits from dapagliflozin rather than weight gain associated with insulin intensification 8
- Both agents can be continued with basal insulin if needed for further intensification 2
Cardiovascular and Renal Benefits
- SGLT2 inhibitors like dapagliflozin provide cardiovascular protection, reducing heart failure hospitalization and cardiovascular death, independent of HbA1c lowering 2
- These benefits extend to patients with chronic kidney disease, making dapagliflozin particularly valuable if renal impairment is present 2
- The decision to use dapagliflozin should be considered independently of baseline HbA1c when cardiovascular or renal comorbidities exist 2
Recommended Treatment Algorithm for HbA1c 8.9%
Step 1: Continue or initiate metformin as foundation therapy (unless contraindicated with GFR <30 mL/min) 9, 3
Step 2: Add dapagliflozin 10 mg plus linagliptin 5 mg as fixed-dose combination once daily 5
Step 3: If already on basal insulin (glargine), continue it at current dose while adding the dapagliflozin/linagliptin combination 2
Step 4: Reassess HbA1c after 3 months—if HbA1c remains >7%, consider initiating or intensifying basal insulin 1, 9
Step 5: Monitor for hypoglycemia if using sulfonylureas concurrently; strongly consider discontinuing sulfonylureas once insulin is established 3
Critical Monitoring Points
- Check renal function before initiating dapagliflozin (requires eGFR >45 mL/min for initiation) 2
- Monitor for genital mycotic infections with SGLT2 inhibitors 2
- Assess for volume depletion, particularly in elderly patients or those on diuretics 2
- Recheck HbA1c at 3 months to determine if additional intensification is needed 1, 9