Glycemic excursions, variability, and hypoglycemia may impact therapeutic effectiveness even when A1C reduction is comparable between therapies. We analyzed masked continuous glucose monitoring (CGM) data from patients with type 2 diabetes (T2D) inadequately controlled on metformin ± sulfonylurea during an international randomized, 24-week, open-label, non-inferiority trial of dapagliflozin plus saxagliptin add-on (DAPA + SAXA, n = 141) compared to titrated insulin glargine add-on (INS, n = 142). Six-day CGM (288 readings/day), A1C and patient-reported outcomes (PRO) were measured at baseline and Weeks 2, 12 and 24. At baseline, patients had mean ± SD age = 55.2 ± 9.4 years; A1C = 9.1 ± 1.1%; diabetes duration = 9.8 ± 6.1 years; 54.1% male. Using linear mixed models, mean ± SE changes in A1C for DAPA + SAXA vs. INS at Week 24 were comparable (−1.75 ± 0.09% vs. −1.63 ± 0.09%, P = 0.33). However, CGM summary analytics were more favorable for DAPA + SAXA: more time in glycemic range, lower glucose variability and less time with nocturnal hypoglycemia (Table 1a). Improvements in CGM at Week 24 correlated with better patient satisfaction and quality of life (n = 225, Table 1b). This analysis of CGM data showed superior diurnal glycemic profiles associated with better PRO for add-on DAPA + SAXA vs. INS in patients with T2D, even though A1C changes were comparable.
Table 1a: Treatment Differences in CGM Summary Analytics --- Table 1b: Correlations of CGM with PRO
| Table 1a. CGM Change from Baseline [Mean (SE)] | DAPA + SAXA + Metformin | INS + Metformin | Difference | P-value | Table 1b. Correlation of Change in CGM with Change in PRO at Week 24 | P-value | |
| Mean 24-hr glucose mg/dL - Week 2 | −48.53 (2.51) | −28.54 (2.51) | −19.99 (3.55) | < 0.0001 | Mean 24-hr glucose mg/dL | Satisfaction | <0.0001 |
| % time glucose ≤ 70 mg/dL - Week 12 | 0.52 (0.38) | 2.29 (0.39) | −1.77 (0.54) | 0.001 | % time > 70 & ≤ 180 mg/dL | Satisfaction | <0.0001 |
| % time glucose ≤ 70 mg/dL 12 to 6 am - Week 24 | 0.60 (0.53) | 2.66 (0.53) | −2.(0.75) | 0.007 | Glycemic Risk Assessment Diabetes Equation (GRADE) | Satisfaction | <0.0001 |
| % time glucose > 70 and ≤ 180 mg/dL - Week 24 | 34.28 (1.89) | 28.50 (1.91) | 5.78 (2.69) | 0.033 | AUC > 180 mg/dL | Satisfaction | 0.001 |
| Mean Amplitude Glycemic Excursion (MAGE) mg/dL - Week 24 | −12.73 (2.26) | −5.01 (2.28) | −7.72 (3.21) | 0.017 | High Blood Glucose Index (HBGI) | Satisfaction | 0.001 |
| Within-Day SD (mg/dL) - Week 24 | −5.93 (0.85) | −0.50 (0.86) | −5.43 (1.21) | < 0.0001 | Within-Day SD (mg/dL) | QOL Weight Interference | 0.001 |
| Low Blood Glucose Index (LBGI) - Week 24 | 0.20 (0.05) | 0.41 (0.05) | −0.20 (0.08) | 0.008 | Within-Day SD (mg/dL) | QOL Composite | 0.020 |
| Table 1a. CGM Change from Baseline [Mean (SE)] | DAPA + SAXA + Metformin | INS + Metformin | Difference | P-value | Table 1b. Correlation of Change in CGM with Change in PRO at Week 24 | P-value | |
| Mean 24-hr glucose mg/dL - Week 2 | −48.53 (2.51) | −28.54 (2.51) | −19.99 (3.55) | < 0.0001 | Mean 24-hr glucose mg/dL | Satisfaction | <0.0001 |
| % time glucose ≤ 70 mg/dL - Week 12 | 0.52 (0.38) | 2.29 (0.39) | −1.77 (0.54) | 0.001 | % time > 70 & ≤ 180 mg/dL | Satisfaction | <0.0001 |
| % time glucose ≤ 70 mg/dL 12 to 6 am - Week 24 | 0.60 (0.53) | 2.66 (0.53) | −2.(0.75) | 0.007 | Glycemic Risk Assessment Diabetes Equation (GRADE) | Satisfaction | <0.0001 |
| % time glucose > 70 and ≤ 180 mg/dL - Week 24 | 34.28 (1.89) | 28.50 (1.91) | 5.78 (2.69) | 0.033 | AUC > 180 mg/dL | Satisfaction | 0.001 |
| Mean Amplitude Glycemic Excursion (MAGE) mg/dL - Week 24 | −12.73 (2.26) | −5.01 (2.28) | −7.72 (3.21) | 0.017 | High Blood Glucose Index (HBGI) | Satisfaction | 0.001 |
| Within-Day SD (mg/dL) - Week 24 | −5.93 (0.85) | −0.50 (0.86) | −5.43 (1.21) | < 0.0001 | Within-Day SD (mg/dL) | QOL Weight Interference | 0.001 |
| Low Blood Glucose Index (LBGI) - Week 24 | 0.20 (0.05) | 0.41 (0.05) | −0.20 (0.08) | 0.008 | Within-Day SD (mg/dL) | QOL Composite | 0.020 |
D.C. Simonson: Advisory Panel; Self; GI Windows, Inc.. Stock/Shareholder; Self; GI Windows, Inc.. Stock/Shareholder; Spouse/Partner; Phase V Technologies, Inc. T. Vilsbøll: None. E. Ekholm: None. E.K. Johnsson: Employee; Self; AstraZeneca. M.A. Testa: Stock/Shareholder; Spouse/Partner; GI Windows, Inc.. Stock/Shareholder; Self; Phase V Technologies, Inc.. S. Jabbour: None. M. Lind: Consultant; Self; AstraZeneca. Research Support; Self; AstraZeneca. Consultant; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Novo Nordisk Inc.. Consultant; Self; Eli Lilly and Company. Research Support; Self; Dexcom, Inc.. Consultant; Self; Eli Lilly and Company. Advisory Panel; Self; MSD K.K.. Research Support; Self; Pfizer Inc.. Consultant; Self; Medtronic.
