Glucose Variables in T1D Studies with Dapagliflozin—Pooled Analysis of Continuous Glucose Monitoring Data from DEPICT-1 and 2

Abstract

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 parametersCGM parameterTreatment armMean 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 mg193.00 (28.78)179.93 (32.41)-8.40 (1.30)−15.48 (−18.82, −12.13)DAPA 10 mg191.00 (28.11)174.87 (26.59)–11.82 (1.32)−18.90 (−22.25, − 15.54)Placebo191.64 (29.04)194.34 (32.62)7.07 (1.33)MAGE (mg/dL)DAPA 5 mg170.53 (30.55)154.67 (34.21)–12.48 (1.37)−13.36 (−16.89, −9.83)DAPA 10 mg171.01 (31.59)154.52 (34.52)–13.06 (1.39)−13.94 (−17.48, −10.40)Placebo168.99 (31.46)166.94 (31.62)0.88 (1.40)Percent of 24-hour glucose values within >70 – ≤180 mg/dL (%)DAPA 5 mg43.38 (12.22)51.69 (14.49)6.48 (0.60)9.07 (7.55, 10.59)DAPA 10 mg43.98 (12.32)53.89 (13.26)8.08 (0.60)10.67 (9.15, 12.20)Placebo43.66 (12.64)43.10 (13.97)–2.59 (0.61)Percent of glucose readings ≤70 mg/dL over 24-hours (%)DAPA 5 mg4.96 (4.64)4.85 (4.89)–0.43 (0.21)0.06 (–0.47, 0.59)DAPA 10 mg5.30 (4.90)5.10 (4.44)–0.33 (0.21)0.16 (–0.38, 0.69)Placebo5.14 (5.56)4.83 (4.72)–0.49 (0.21)Percent of glucose readings ≤54 mg/dL (%)DAPA 5 mg2.22 (2.87)2.02 (2.83)–0.32 (0.13)–0.14 (–0.47, 0.19)DAPA 10 mg2.34 (3.13)2.05 (2.63)–0.34 (0.13)–0.16 (–0.48, 0.17)Placebo2.28 (3.82)2.15 (3.15)–0.19 (0.13)Postprandial glucose readings by CGM (mg/dL)DAPA 5 mg199.42 (40.51)192.97 (43.90)–0.85 (1.99)–8.55 (–13.70, –3.41)DAPA 10 mg196.61 (38.57)186.93 (36.21)–5.05 (2.02)–12.76 (–17.93, –7.58)Placebo197.35 (42.32)199.68 (44.36)7.70 (2.03)Percent of nocturnal (00:00–05:59) glucose values ≤70 mg/dL (%)DAPA 5 mg5.94 (7.64)5.95 (8.26)–0.38 (0.36)–0.15 (–1.07, 0.78)DAPA 10 mg5.52 (7.22)6.00 (7.60)–0.18 (0.37)0.06 (–0.87, 0.99)Placebo5.83 (7.74)5.85 (7.64)–0.24 (0.37) Disclosure C. Mathieu: Research Support; Self; Novo Nordisk A/S. Advisory Panel; Self; Novo Nordisk A/S. Speaker's Bureau; Self; Novo Nordisk A/S. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Merck Sharp & Dohme Corp.. Speaker's Bureau; Self; Merck Sharp & Dohme Corp.. Advisory Panel; Self; Merck Sharp & Dohme Corp.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Novartis AG. Speaker's Bureau; Self; Novartis AG. Advisory Panel; Self; Novartis AG, Bristol-Myers Squibb Company. Speaker's Bureau; Self; AstraZeneca. Advisory Panel; Self; AstraZeneca, Pfizer Inc., Janssen Pharmaceuticals, Inc., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Hanmi Pharmaceutical. Research Support; Self; Roche Diagnostics Corporation. Advisory Panel; Self; Roche Diagnostics Corporation. Research Support; Self; Medtronic. Advisory Panel; Self; Medtronic, MannKind Corporation. Research Support; Self; Intrexon. Advisory Panel; Self; Intrexon, Dianax, UCB, Inc.. Research Support; Self; Abbott. P. Dandona: Advisory Panel; Self; AstraZeneca. Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. M. Phillip: Other Relationship; Self; Sanofi, Medtronic MiniMed, Inc., Novo Nordisk A/S. Speaker's Bureau; Self; Eli Lilly and Company. Research Support; Self; Merck & Co., Inc., Bristol-Myers Squibb Company, Kamada, Lexicon Pharmaceuticals, Inc.. Other Relationship; Self; DreaMed Diabetes, Ltd.. Speaker's Bureau; Self; Abbott. T. Oron: None. L. Hansen: Employee; Self; MedImmune. F.A. Thoren: Employee; Self; AstraZeneca. J. Xu: Employee; Self; AstraZeneca. A. Langkilde: Employee; Self; AstraZeneca. Stock/Shareholder; Self; AstraZeneca.