Table 1:
Phase 3 Randomized Trials of SGLT Inhibitors in T1DM
| Trial/Agent/NCT | Number of participants | Duration of trial (weeks) | HbA1c change* | Weight change* | TDD change* | Severe hypoglycemia | DKA | Genital mycotic infections |
|---|---|---|---|---|---|---|---|---|
| DEPICT-1 24 weeks Dapagliflozin NCT02268214 27 | N=833; n=277 5 mg, n=296 10 mg, n=260 placebo | 24 | 5 mg: −0.42% (p<0.0001) 10 mg: −0.45% (p<0.0001) | 5 mg: −2.96% (p<0.0001) 10 mg: −3.72% (p<0.0001) | 5 mg: −8.8% (p<0.0001) 10 mg: −13.2% (p<0.0001) | 5 mg: 8% 10 mg: 6% Placebo: 7% | 5 mg: 1% 10 mg: 2% Placebo: 1% | 5 mg: 12% 10 mg: 11% Placebo: 3% |
| DEPICT-1 52-week extension Dapagliflozin NCT02268214 28 | N=708; n=235 5 mg, n=255 10 mg, n=218 placebo | 52 | 5 mg: −0.33% (95% CI −0.49,−0.17) 10 mg: −0.36% (95% CI −0.53,−0.20) | 5 mg: −2.95% (95% CI −3.83,−2.06) 10 mg: −4.54% (95% CI −5.40,−3.66) | Decrease at 24 weeks maintained | 5 mg: 10.5% 10 mg: 8.4% Placebo: 11.5% | 5 mg: 4.0% 10 mg: 3.4% Placebo: 1.9% | 5 mg: 15.5% 10 mg: 13.5% Placebo: 3.1% |
| DEPICT-2 Dapagliflozin NCT02460978 29 | N=813; n=271 5 mg, n=270 10 mg, n=272 placebo | 24 | 5 mg: −0.37% (p<0.0001) 10 mg: −0.42% (p<0.0001) | 5 mg: −3.21% (p<0.0001) 10 mg: −3.71% (p<0.0001) | 5 mg: −10.78% (p<0.0001) 10 mg: −11.08% (p<0.0001) | 5 mg: 6.3% 10 mg: 8.5% Placebo: 7.7% | 5 mg: 2.6% 10 mg: 2.2% Placebo: 0% | 5 mg: 10.0% 10 mg: 7.8% Placebo: 1.8% |
| DEPICT-2 52-week extension Dapagliflozin NCT02460978 30 | n=717, n=231 5 mg, n=226 10 mg, n=216 placebo | 52 | 5 mg: −0.20% (95% CI −0.34,−0.06) 10 mg: −0.25% (95% CI −0.38,−0.11) | 5 mg: −4.42% (95% CI −5.19,−3.64) 10 mg: −4.86% (95% CI −5.63,−4.08) | Decrease at 24 weeks maintained | 5 mg: 8.9% 10 mg: 9.6% Placebo: 8.5% | 5 mg: 4.1% 10 mg: 3.7% Placebo: 0.4% | 5 mg: 11.1% 10 mg: 10.4% Placebo: 3.7% |
| EASE-2 Empagliflozin NCT02414958 31 | N=723; n=243 10 mg, n=241 25 mg, n=239 placebo | 26 | 10 mg: −0.54% (p<0.0001) 25 mg: −0.53% (p<0.0001) | 10 mg: −2.7kg (p<0.0001) 25 mg: −3.3kg (p<0.0001) | 10 mg: −13.3% (p<0.0001) 25 mg: −12.7% (p<0.0001) | See Pooled Data | See Pooled Data | See Pooled Data |
| EASE-2 52-week extension Empagliflozin NCT02414958 31 | N=617; n=204 10 mg, n=220 25 mg, n=193 placebo | 52 | 10 mg: −0.39% (p<0.0001) 25 mg: −0.45% (p<0.0001) | 10 mg: −3.2kg (p<0.0001) 25 mg: −3.6kg (p<0.0001) | 10 mg: −12.0% (p<0.0001) 25 mg: −12.9% (p<0.0001) | See Pooled Data | See Pooled Data | See Pooled Data |
| EASE-3 Empagliflozin NCT02580591 31 | N=961; n=237 2.5 mg, n=244 10 mg, n=242 25 mg, n=238 placebo | 26 | 2.5 mg: −0.28% (p<0.0001) 10 mg: −0.45% (p<0.0001) 25 mg: −0.52% (p<0.0001) | 2.5 mg: −1.8kg (p<0.0001) 10 mg: −3.0kg (p<0.0001) 25 mg: −3.4kg (p<0.0001) | 2.5 mg: −6.4% (p<0.0001) 10 mg: −9.5% (p<0.0001) 25 mg: −12.6% (p<0.0001) | 2.5 mg: 1.2% Placebo: 2.5% See Pooled Data for 10 mg and 25 mg | 2.5 mg: 0.8% Placebo: 1.2% See Pooled Data for 10 mg and 25 mg | 2.5 mg: 5.4% Placebo: 2.5% See Pooled Data for 10 mg and 25 mg |
| EASE-2 and EASE3 Pooled Empagliflozin NCT02414958, NCT02580591 31 | N=1464; n=491 10 mg, n=489 25 mg, n=484 placebo | 26 | Not reported | Not reported | Not reported | 10 mg: 4.1% 25 mg: 2.7% Placebo: 3.1% | 10 mg: 4.3% 25 mg: 3.3% Placebo: 1.2% | 10mg: 12.8% 25 mg: 14.3% Placebo: 4.3% |
| Kaku et al Ipragliflozin NCT02897219 25,30 | N=174; n=115 50 mg, n=59 placebo | 24** | 50 mg: −0.36% (p=0.001) | 50 mg: −2.87kg (p<0.001) | 50 mg: −15.26% (p<0.001) | 50 mg: 1.7% Placebo: 0.0% | 50 mg: 0.0% Placebo: 0.0% | 50 mg: 5.2% Placebo: 0.0% |
| InTandem-1 Sotagliflozin NCT02384941 33 | N=793; n=263 200 mg, n=262 400 mg, N=268 placebo | 24 | 200 mg: −0.36% (p<0.001) 400 mg: −0.41% (p<0.001) | 200 mg: −2.3kg (p<0.001) 400 mg: −3.4kg (p<0.001) | 200 mg: −6.16% (p<0.001) 400 mg: −9.70% (p<0.001) | See 52-week data | See 52-week data | See 52-week data |
| InTandem-1 52week extension Sotagliflozin NCT02384941 33 | N=793; n=263 200 mg, n=262 400 mg, n=268 placebo | 52 | 200 mg: −0.25% (p<0.001) 400 mg: −0.31% (p<0.001) | 200 mg: −3.1kg (p<0.001) 400 mg: −4.3kg (p<0.001) | 200 mg: −8.02% (p<0.001) 400 mg: −12.64% (p<0.001) | 200 mg: 6.5% 400 mg: 6.5% Placebo: 9.7% | 200 mg: 3.4% 400 mg: 4.2% Placebo: 0.4% | 200 mg: 9.1% 400 mg: 13.0% Placebo: 3.4% |
| InTandem-2 Sotagliflozin NCT02421510 34 | N=782; n=261 200 mg, n=263 400 mg, n=258 placebo | 24 | 200 mg: −0.37% (p<0.001) 400 mg: −0.35% (p<0.001) | 200 mg: −2.0kg (p<0.001) 400 mg: −2.6kg (p<0.001) | 200 mg: −8.23% (p<0.001) 400 mg: −9.47% (p<0.001) | See 52-week data | See 52-week data | See 52-week data |
| InTandem-2 52week extension Sotagliflozin NCT02421510 34 | N=782; n=261 200 mg, n=263 400 mg, n=258 placebo | 52 | 200 mg: −0.21% (p<0.001) 400 mg: −0.32% (p<0.001) | 200 mg: −2.2kg (p<0.001) 400 mg: −2.9kg (p<0.001) | 200mg: −6.26% (p=0.002) 400mg −8.17% (p<0.001) | 200 mg: 5.0% 400 mg: 2.3% Placebo: 5.0% | 200 mg: 2.3% 400 mg: 3.4% Placebo: 0% | 200 mg: 9.2% 400 mg: 11.0% Placebo: 2.3% |
| InTandem-3 Sotagliflozin4 | N=1402; n=699 400 mg, n=703 placebo | 24 | 400 mg: −0.46% (p<0.001) | 400 mg: −3.0kg (p<0.001) | 400 mg: −9.7% (p<0.001) | 400 mg: 3.0% Placebo: 2.4% | 400 mg: 3.0% Placebo: 0.6% | 400 mg: 6.4% Placebo: 2.1% |
*
compared with placebo
**
Note 28 week open-label extension study with placebo cross-over to active treatment plus dose escalation of both groups at 32 weeks, not included in table; described above30