Improved glycemic control and weight loss, without increased hypoglycemia, were demonstrated in two short-term, 24-week, Phase 3 studies of the SGLT2 inhibitor dapagliflozin (DAPA) as adjunct to adjustable insulin in patients with inadequately controlled T1D (DEPICT-1 and 2). In this post-hoc analysis we pooled continuous glucose monitoring (CGM) data at baseline and week 24 from both studies. In total, 1591 patients were included (DAPA 5 mg N=530; DAPA 10 mg N=529; placebo N=532). Baseline characteristics were comparable between the study groups. DAPA treatment significantly reduced mean interstitial glucose, mean amplitude of glucose excursions (MAGE), and postprandial glucose, while expanding the time in glycemic target range (>70 mg/dL to ≤180 mg/dL)(Table). In addition, DAPA treatment did not increase the percent of glucose readings ≤70 mg/dL or ≤54 mg/dL, or the percent of readings ≤70 mg/dL in the nocturnal period (00:00 to 05:59). These results demonstrate that DAPA as adjunct to insulin in patients with T1D reduced glycemic variability without increasing time in the hypoglycemia range.
Table. Pooled CGM parameters
| CGM parameter | Treatment arm | Mean baseline value (SD) | Mean Week 24 value (SD) | Adjusted mean change from baseline (SE) | Difference vs. placebo (95% CI) |
| Mean 24-hour glucose readings (mg/dL) | DAPA 5 mg | 193.00 (28.78) | 179.93 (32.41) | -8.40 (1.30) | −15.48 (−18.82, −12.13) |
| DAPA 10 mg | 191.00 (28.11) | 174.87 (26.59) | –11.82 (1.32) | −18.90 (−22.25, − 15.54) | |
| Placebo | 191.64 (29.04) | 194.34 (32.62) | 7.07 (1.33) | ||
| MAGE (mg/dL) | DAPA 5 mg | 170.53 (30.55) | 154.67 (34.21) | –12.48 (1.37) | −13.36 (−16.89, −9.83) |
| DAPA 10 mg | 171.01 (31.59) | 154.52 (34.52) | –13.06 (1.39) | −13.94 (−17.48, −10.40) | |
| Placebo | 168.99 (31.46) | 166.94 (31.62) | 0.88 (1.40) | ||
| Percent of 24-hour glucose values within >70 – ≤180 mg/dL (%) | DAPA 5 mg | 43.38 (12.22) | 51.69 (14.49) | 6.48 (0.60) | 9.07 (7.55, 10.59) |
| DAPA 10 mg | 43.98 (12.32) | 53.89 (13.26) | 8.08 (0.60) | 10.67 (9.15, 12.20) | |
| Placebo | 43.66 (12.64) | 43.10 (13.97) | –2.59 (0.61) | ||
| Percent of glucose readings ≤70 mg/dL over 24-hours (%) | DAPA 5 mg | 4.96 (4.64) | 4.85 (4.89) | –0.43 (0.21) | 0.06 (–0.47, 0.59) |
| DAPA 10 mg | 5.30 (4.90) | 5.10 (4.44) | –0.33 (0.21) | 0.16 (–0.38, 0.69) | |
| Placebo | 5.14 (5.56) | 4.83 (4.72) | –0.49 (0.21) | ||
| Percent of glucose readings ≤54 mg/dL (%) | DAPA 5 mg | 2.22 (2.87) | 2.02 (2.83) | –0.32 (0.13) | –0.14 (–0.47, 0.19) |
| DAPA 10 mg | 2.34 (3.13) | 2.05 (2.63) | –0.34 (0.13) | –0.16 (–0.48, 0.17) | |
| Placebo | 2.28 (3.82) | 2.15 (3.15) | –0.19 (0.13) | ||
| Postprandial glucose readings by CGM (mg/dL) | DAPA 5 mg | 199.42 (40.51) | 192.97 (43.90) | –0.85 (1.99) | –8.55 (–13.70, –3.41) |
| DAPA 10 mg | 196.61 (38.57) | 186.93 (36.21) | –5.05 (2.02) | –12.76 (–17.93, –7.58) | |
| Placebo | 197.35 (42.32) | 199.68 (44.36) | 7.70 (2.03) | ||
| Percent of nocturnal (00:00–05:59) glucose values ≤70 mg/dL (%) | DAPA 5 mg | 5.94 (7.64) | 5.95 (8.26) | –0.38 (0.36) | –0.15 (–1.07, 0.78) |
| DAPA 10 mg | 5.52 (7.22) | 6.00 (7.60) | –0.18 (0.37) | 0.06 (–0.87, 0.99) | |
| Placebo | 5.83 (7.74) | 5.85 (7.64) | –0.24 (0.37) |
| CGM parameter | Treatment arm | Mean baseline value (SD) | Mean Week 24 value (SD) | Adjusted mean change from baseline (SE) | Difference vs. placebo (95% CI) |
| Mean 24-hour glucose readings (mg/dL) | DAPA 5 mg | 193.00 (28.78) | 179.93 (32.41) | -8.40 (1.30) | −15.48 (−18.82, −12.13) |
| DAPA 10 mg | 191.00 (28.11) | 174.87 (26.59) | –11.82 (1.32) | −18.90 (−22.25, − 15.54) | |
| Placebo | 191.64 (29.04) | 194.34 (32.62) | 7.07 (1.33) | ||
| MAGE (mg/dL) | DAPA 5 mg | 170.53 (30.55) | 154.67 (34.21) | –12.48 (1.37) | −13.36 (−16.89, −9.83) |
| DAPA 10 mg | 171.01 (31.59) | 154.52 (34.52) | –13.06 (1.39) | −13.94 (−17.48, −10.40) | |
| Placebo | 168.99 (31.46) | 166.94 (31.62) | 0.88 (1.40) | ||
| Percent of 24-hour glucose values within >70 – ≤180 mg/dL (%) | DAPA 5 mg | 43.38 (12.22) | 51.69 (14.49) | 6.48 (0.60) | 9.07 (7.55, 10.59) |
| DAPA 10 mg | 43.98 (12.32) | 53.89 (13.26) | 8.08 (0.60) | 10.67 (9.15, 12.20) | |
| Placebo | 43.66 (12.64) | 43.10 (13.97) | –2.59 (0.61) | ||
| Percent of glucose readings ≤70 mg/dL over 24-hours (%) | DAPA 5 mg | 4.96 (4.64) | 4.85 (4.89) | –0.43 (0.21) | 0.06 (–0.47, 0.59) |
| DAPA 10 mg | 5.30 (4.90) | 5.10 (4.44) | –0.33 (0.21) | 0.16 (–0.38, 0.69) | |
| Placebo | 5.14 (5.56) | 4.83 (4.72) | –0.49 (0.21) | ||
| Percent of glucose readings ≤54 mg/dL (%) | DAPA 5 mg | 2.22 (2.87) | 2.02 (2.83) | –0.32 (0.13) | –0.14 (–0.47, 0.19) |
| DAPA 10 mg | 2.34 (3.13) | 2.05 (2.63) | –0.34 (0.13) | –0.16 (–0.48, 0.17) | |
| Placebo | 2.28 (3.82) | 2.15 (3.15) | –0.19 (0.13) | ||
| Postprandial glucose readings by CGM (mg/dL) | DAPA 5 mg | 199.42 (40.51) | 192.97 (43.90) | –0.85 (1.99) | –8.55 (–13.70, –3.41) |
| DAPA 10 mg | 196.61 (38.57) | 186.93 (36.21) | –5.05 (2.02) | –12.76 (–17.93, –7.58) | |
| Placebo | 197.35 (42.32) | 199.68 (44.36) | 7.70 (2.03) | ||
| Percent of nocturnal (00:00–05:59) glucose values ≤70 mg/dL (%) | DAPA 5 mg | 5.94 (7.64) | 5.95 (8.26) | –0.38 (0.36) | –0.15 (–1.07, 0.78) |
| DAPA 10 mg | 5.52 (7.22) | 6.00 (7.60) | –0.18 (0.37) | 0.06 (–0.87, 0.99) | |
| Placebo | 5.83 (7.74) | 5.85 (7.64) | –0.24 (0.37) |
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