Rates and aHRs (95% CIs) for lactic acidosis hospitalizations among patients with reduced GFR who used metformin vs. sulfonylureas in weighted cohort
| . | Metformin . | Sulfonylureas . |
|---|---|---|
| Number at risk matched weighted | 24,542 | 24,662 |
| Primary outcome: lactic acidosis hospitalization | 193 | 180 |
| Person-years | 46,197 | 48,748 |
| Unadjusted rate/1,000 person-years (95% CI) | 4.18 (3.63, 4.81) | 3.69 (3.19, 4.27) |
| aHRb (95% CI) | 1.21 (0.99, 1.48) | Reference |
| Laboratory-confirmed lactic acid hospitalization | 84 | 75 |
| Person-years | 46,283 | 48,860 |
| Unadjusted rate/1,000 person-years (95% CI) | 1.81 (1.46, 2.24) | 1.54 (1.23, 1.93) |
| aHRb (95% CI) | 1.25 (0.92, 1.70) | Reference |
| Primary discharge diagnosis of lactic acidosis hospitalization | 122 | 121 |
| Person-years | 46,250 | 48,785 |
| Unadjusted rate/1,000 person-years (95% CI) | 2.63 (2.20, 3.14) | 2.49 (2.08, 2.97) |
| aHRb (95% CI) | 1.11 (0.87, 1.44) | Reference |
| Sensitivity analysis: requiring lactate ≥5 mmol/L | ||
| Number at risk matched weighted | 24,542 | 24,662 |
| Composite lactic acidosis hospitalizations | 146 | 140 |
| Person-years | 46,238 | 48,769 |
| Unadjusted rate/1,000 person-years (95% CI) | 3.16 (2.69, 3.72) | 2.89 (2.45, 3.41) |
| aHRb (95% CI) | 1.15 (0.91, 1.46) | Reference |
| Sensitivity analysis: population with second reduced eGFR | ||
| Number at risk matched weighted | 3,851 | 3,872 |
| Composite lactic acidosis hospitalizations | 22 | 27 |
| Person-years | 7,160 | 8,487 |
| Unadjusted rate/1,000 person-years (95% CI) | 3.07 (2.02, 4.64) | 3.17 (2.18, 4.60) |
| aHRb (95% CI) | 1.09 (0.64, 1.84) | Reference |
| Sensitivity analysis: excluding Medicare Advantage | ||
| Number at risk matched weighteda | 20,787 | 20,893 |
| Composite lactic acidosis hospitalizations | 163 | 154 |
| Person-years | 37,216 | 39,507 |
| Unadjusted rate/1,000 person-years (95% CI) | 3.89 (3.33, 4.56) | 4.37 (3.75, 5.10) |
| aHR (95% CI)b | 1.18 (0.94, 1.47) | Reference |
| . | Metformin . | Sulfonylureas . |
|---|---|---|
| Number at risk matched weighted | 24,542 | 24,662 |
| Primary outcome: lactic acidosis hospitalization | 193 | 180 |
| Person-years | 46,197 | 48,748 |
| Unadjusted rate/1,000 person-years (95% CI) | 4.18 (3.63, 4.81) | 3.69 (3.19, 4.27) |
| aHRb (95% CI) | 1.21 (0.99, 1.48) | Reference |
| Laboratory-confirmed lactic acid hospitalization | 84 | 75 |
| Person-years | 46,283 | 48,860 |
| Unadjusted rate/1,000 person-years (95% CI) | 1.81 (1.46, 2.24) | 1.54 (1.23, 1.93) |
| aHRb (95% CI) | 1.25 (0.92, 1.70) | Reference |
| Primary discharge diagnosis of lactic acidosis hospitalization | 122 | 121 |
| Person-years | 46,250 | 48,785 |
| Unadjusted rate/1,000 person-years (95% CI) | 2.63 (2.20, 3.14) | 2.49 (2.08, 2.97) |
| aHRb (95% CI) | 1.11 (0.87, 1.44) | Reference |
| Sensitivity analysis: requiring lactate ≥5 mmol/L | ||
| Number at risk matched weighted | 24,542 | 24,662 |
| Composite lactic acidosis hospitalizations | 146 | 140 |
| Person-years | 46,238 | 48,769 |
| Unadjusted rate/1,000 person-years (95% CI) | 3.16 (2.69, 3.72) | 2.89 (2.45, 3.41) |
| aHRb (95% CI) | 1.15 (0.91, 1.46) | Reference |
| Sensitivity analysis: population with second reduced eGFR | ||
| Number at risk matched weighted | 3,851 | 3,872 |
| Composite lactic acidosis hospitalizations | 22 | 27 |
| Person-years | 7,160 | 8,487 |
| Unadjusted rate/1,000 person-years (95% CI) | 3.07 (2.02, 4.64) | 3.17 (2.18, 4.60) |
| aHRb (95% CI) | 1.09 (0.64, 1.84) | Reference |
| Sensitivity analysis: excluding Medicare Advantage | ||
| Number at risk matched weighteda | 20,787 | 20,893 |
| Composite lactic acidosis hospitalizations | 163 | 154 |
| Person-years | 37,216 | 39,507 |
| Unadjusted rate/1,000 person-years (95% CI) | 3.89 (3.33, 4.56) | 4.37 (3.75, 5.10) |
| aHR (95% CI)b | 1.18 (0.94, 1.47) | Reference |
Primary analysis considers patients persistent on regimen until they do not have oral antidiabetic medications for 90 days.
Cox proportional hazards model for time to event. Adjusted for mean-centered metformin dose, demographics, clinical information derived from the electronic health record, comorbidities, use of medications, and health care utilization (see Supplementary Table 1). All continuous variables were modeled as restricted cubic splines.