Table 2.
SGLT2 inhibitors: clinical efficacy and safety
| Canagliflozin | Dapagliflozin | Empagliflozin | Ertugliflozin | |
|---|---|---|---|---|
| Baseline HbA1c | 7.94–7.96% | 7.9–8.2% | 7.9% | 8.1–8.2% |
| Baseline HbA1c (mmol/mol) | 63 | 63–66 | 63 | 65–66 |
| Δ HbA1c (low dose) | −0.62% (100 mg) | −0.4% (5 mg) | −0.6% (10 mg) | −0.5% (5 mg) |
| Δ HbA1c (low dose) (mmol/mol) | −7 (100 mg) | −4 (5 mg) | −7 (10 mg) | −6 (5 mg) |
| Δ HbA1c (high dose) | −0.77% (300 mg) | −0.5% (10 mg) | −0.6% (25 mg) | −0.7% (15 mg) |
| Δ HbA1c (high dose) (mmol/mol) | −9 (300 mg) | −6 (10 mg) | −7 (25 mg) | −8 (15 mg) |
| Δ Weight (low dose) | −2.5% (100 mg) | −2.2 kg (5 mg) | −2.0% (10 mg) | −1.8 kg (5 mg) |
| Δ Weight (high dose) | −2.9% (300 mg) | −2.0 kg (10 mg) | −2.5% (25 mg) | −1.7 kg (15 mg) |
| Δ Systolic BP (low dose) | −3.7 mmHg (100 mg) | −4.5 mmHg (5 mg) | −4.1 mmHg (10 mg) | −3.3 mmHg (5 mg) |
| Δ Systolic BP (high dose) | −5.4 mmHg (300 mg) | −5.3 mmHg (10 mg) | −4.8 mmHg (25 mg) | −3.8 mmHg (15 mg) |
| CV outcome trial* | CANVAS | DECLARE-TIMI 58 | EMPA-REG OUTCOME | |
| MACE risk reduction | 0.86 (0.75–0.97) | 0.93 (0.84–1.03) | 0.86 (0.74–0.99) | |
| Heart failure (hospitalization) | 0.67 (0.52–0.87) | 0.73 (0.61–0.88) | 0.65 (0.50–0.85) | |
| Death (CV) | 0.87 (0.72–1.06) | 0.98 (0.82–1.17) | 0.62 (0.49–0.77) | |
| Death (any cause) | 0.87 (0.74–1.01) | 0.93(0.82–1.03) | 0.68 (0.57–0.82) | |
| Nonfatal MI (except silent MI) | 0.85 (0.69–1.05) | 0.89(0.77–1.01) | 0.87 (0.70–1.09) | |
| Nonfatal stroke | 0.90 (0.71–1.15) | 1.01 (0.84–1.21) | 1.24 (0.92–1.67) | |
| Progression of kidney disease | 0.73 (0.67–0.79) | 0.53 (0.43–0.66) | 0.61 (0.53–0.70) |
Four SGLT2 inhibitors have been approved by the U.S. FDA for the treatment of type 2 diabetes. Data have been taken from the FDA-approved prescribing information for each drug and/or from the cardiovascular (CV) outcome trials (1–3,53). The prescribing information expresses HbA1c as a percent (NGSP units). HbA1c levels in International Federation of Clinical Chemistry (IFFC) units (mmol/mol) were generated using the conversion tool at http://www.ngsp.org/convert1.asp, which uses the following equation for the conversion: NGSP = (0.09148 × IFCC) + 2.152. Accordingly, it is not straightforward to accomplish the conversion for mean Δ HbA1c. For purposes of the article, we have estimated Δ HbA1c (mmol/mol) by assuming that the baseline HbA1c was ∼8.0% (64 mmol/mol) and calculating the change in HbA1c if that baseline HbA1c were decreased by reported change in HbA1c. For example, if the prescribing information reports that Δ HbA1c = −0.6%, this would correspond to an HbA1c of 7.4% (relative to a baseline HbA1c of 8.0%). The website converts an HbA1c of 7.4% to 57 mmol/mol. Thus, we have subtracted 64 mmol/mol from 57 mmol/mol, thereby converting a value of Δ HbA1c = −0.6% to Δ HbA1c = −7 mmol/mol. This should be viewed as an approximation. It would be necessary to convert data on individual patients before averaging to accomplish an exact unit conversion. BP, blood pressure; MI, myocardial infarction.
*For the CV outcome trials, data are hazard ratio (95% CI). Because the CV outcome study for ertugliflozin is still in progress, data are not yet available.