Table 1.
A Summary of Trials in the Use of SGLTi as Adjunct to Insulin Therapy in T1D.
| Study | Doses used | Length of study | Population | HbA1c change from baseline | Total daily dose: change from baseline | Body Weight: change from baseline | Systolic blood pressure: change from baseline | Time in range (3.9-10.0 mmol/L): change from baseline | DKA rates per group |
|---|---|---|---|---|---|---|---|---|---|
| Canagliflozin | |||||||||
| NCT0213994359,60 | 100 mg, 300 mg | 18 weeks | HbA1c 7-9%, aged 25-65, low C-peptide, BMI 21-35 kg/m2 n = 351 | 100 mg: −0.27% 300 mg: −0.24% P: +0.01% | Measured as Units/day: 100 mg: −2.5 300 mg: −6.0 P: +1.6 | As % from baseline 100 mg: −3.1 300 mg: −5.1 P: +0.3 | N/A | 100 mg: +11.7 300 mg: + 10.1 P: −3.5 | 100 mg: 4.3% 300 mg: 6% P: 0% |
| Dapagliflozin | |||||||||
| DEPICT-165,75 | 5 mg, 10 mg | 24 weeks 65 52 weeks 75 NB: 24-week data shown if not clearly stated in 52-week data | HbA1c 7.7-11%, aged 18-75, low C peptide (exclusion if BMI < 18.5, < 0.3 U/kg, recent hypoglycemia or polyuria/polydipsia/ weight loss) DEPICT-1, n = 833 DEPICT-2, n = 814 | P-adjusted at 52 weeks: 5 mg: −0.33% 10 mg: −0.36% | P-adjusted at 24 weeks: 5 mg: −8.8% 10 mg −13.2% | P-adjusted at 52 weeks:5 mg: −2.95% 10 mg: −4.54% | P-adjusted at 52 weeks: 5 mg: −1.12 mmHg (NS) 10 mg: −5.38 mmHg (NS) | At 24 weeks:5 mg: + 7.0 10 mg: + 8.5 P: −2.1% | 5 mg: 4.5% 10 mg: 3.4% P: 1.9% |
| DEPICT-2 68 | 24 weeks 68 52 weeks, as pooled analyses 62 NB: 24-week data shown | P-adjusted: 5 mg: −0.37% 10 mg: −0.42% | P-adjusted: 5 mg: −10.78% 10 mg: −11.08% | P-adjusted: 5 mg: −3.2% 10 mg: −3.74% | N/A | P-adjusted at 24 weeks 5 mg: + 9.0% 10 mg: +10.7% | 5 mg: 2.6% 10 mg:2.2% P: 0% | ||
| DEPICT-5 76 | 52 weeks | Japanese, HbA1c 7.5-10.5%, age 18-75 years old, BMI ≥ 20 kg/m2, low C-peptide, TDD ≥ 0.3 U/kg/day n = 151 | P-adjusted 5 mg: −0.33% 10 mg: −0.36% | P-adjusted, % from baseline 5 mg: −12.27 10 mg: −13.13 | P-adjusted, % from baseline 5 mg: −4.25 10 mg: −5.96 | N/A | N/A | 5 mg: 2.6% (2 patients) 10 mg: 1.3% (1 patient) P: 0% | |
| Sotagliflozin | |||||||||
| InTandem1 66 | 200 mg, 400 mg | 52 weeks | HbA1c 7-11%, >18 years old, BMI >18.5, exclusion if recent severe hypoglycemia or DKA InTandem1, n = 793 patients (North America) InTandem2, n = 782 (Europe and Israel) InTandem3, n = 1402 (world-wide, 133 sites) | P-adjusted 200 mg: −0.36% 400 mg: −0.41% | P-adjusted 200 mg: −8.02% 400 mg: −12.64 % | P-adjusted 200 mg: −3.63% 400 mg: −4.96 % | P-adjusted 200 mg: −2.8 mmHg 400 mg: −4.4 mmHg | 400 mg: +10.4% P: +2.5% | 200 mg: 3.4% 400 mg: 4.2% P: 0.4% |
| InTandem2 74 | 200 mg, 400 mg | 52 weeks | P-adjusted: 200 mg: −0.21% 400 mg: −0.32% | P-adjusted 200 mg: −6.26% 400 mg: −8.17% | P-adjusted 200 mg: −2.78% 400 mg: −3.50% | At 12 weeks 400 mg: −2.8 mmHg (200 mg data not given) | P-adjusted 200 mg: +8.4 400 mg: +13.4 | 200 mg: 2.3% 400 mg: 3.4% P:0% | |
| InTandem3 63 | 400 mg | 24 weeks | P-adjusted: −0.46% | P-adjusted: −9.7% | P-adjusted: −2.98 kg | 400 mg: −3.5 mmHg | N/A | 400 mg: 3% P: 0.6% | |
| InTandem4 69 | 75 mg, 200 mg, 400 mg | 12 weeks | ≥18 years old, HbA1c 7.0-10.0%, GFR > 60 ml/min/1.73 m2 n = 141 | P-adjusted from baseline 75 mg: −0.3 (NS) 200 mg: −0.5 400 mg: −0.4 | P-adjusted, 400 mg: −8.9 Units/day (others not reported, NS) | P-adjusted 75 mg: −1.3 kg 200 mg: −2.4 kg 400 mg: −2.6 kg | P-adjusted 400 mg: −6.1 mmHg (others not reported, NS) | N/A | 400 mg: 1 case (only case in trial) |
| Sotagliflozin JDRF 67 | 400 mg | 12 weeks | Aged 18-30, HbA1c ≥ 9% n = 85 | P-adjusted: −0.4 (NS) | P-adjusted −6.7 (NS) | P-adjusted −2.37 kg | N/A | P-adjusted: 7.7% (NS, P = .057) | 1 subject in 400 mg group only |
| Empagliflozin | |||||||||
| EASE-2,3 (pooled data) 64 | 2.5 mg (EASE-3 only), 10 mg, 25 mg | EASE-2 = 52 weeks EASE-3 = 26 weeks | Low C-peptide, TDD 0.3-1.5 U/kg, BMI ≥ 18.5, GFR ≥ 30 and A1c 7.5-10% after optimization EASE-2 = 723 EASE-3 = 961 | P-adjusted 2.5 mg: −0.28 10 mg: −0.54 25 mg: −0.53 | P-adjusted, % from baseline 2.5 mg: −6.4% 10 mg: −13.3% 25 mg: −12.7% | P-adjusted, in kg 2.5 mg: −1.8 10 mg: −3.0 25 mg: −3.4 | P-adjusted 2.5 g: −2.1 10 mg: −3.9 25 mg: −3.7 | P-adjusted: 2.5 mg: +4.2% (NS) 10 mg: +12.1% 25 mg: +12.9% | 2.5 mg: 0.8% 10 mg: 4.3% 25 mg: 3.3% P: 1.2% |
Note that units of reporting were heterogenous among some trials. (eg, percent change versus change in kilograms for weight).
Abbreviations: N/A, not available; NB, nota bene; NS, not significant; P, placebo.