Author Block: CHANTAL  MATHIEU, PARESH DANDONA, PIETER GILLARD, PETER A. SENIOR, CHRISTOPH HASSLACHER, EIICHI ARAKI,

 

MARCUS LIND, Sweden 

 

STEPHEN C. BAIN, SERGE JABBOUR, NIKI ARYA,

 

FREDRIK A. THOREN, Sweden 

 

ANNA MARIA LANGKILDE, ON BEHALF OF THE DEPICT-2 INVESTIGATORS, Leuven, Belgium, Buffalo, NY,  Edmonton, AB, Canada, Heidelberg, Germany, Kumamoto, Japan, Gothenburg, Sweden, Swansea, United Kingdom, Philadelphia, PA,  Gaithersburg, MD, Mölndal, Sweden

 

The DEPICT-2 trial (NCT02460978) evaluated the efficacy and safety of dapagliflozin (DAPA) as add-on to adjustable insulin (INS) in patients (pts) with inadequately controlled T1D (A1c 7.5-10.5%) over 24 weeks.

 

This phase 3 study randomized pts 1:1:1 to DAPA 5 mg (n=271), 10 mg (n=270) or placebo (PBO; n=272) plus INS. INS dose could be adjusted by the investigator according to self-monitored blood glucose readings, local guidance and individual circumstances.

 

At Week 24, DAPA 5 and 10 mg significantly decreased A1c (0.37% and 0.42% reductions in the DAPA 5 mg and 10 mg groups respectively), total daily insulin dose (TDD), and body weight (Table).

 

As measured by masked continuous glucose monitoring (CGM), mean interstitial glucose, mean amplitude of glucose excursion (MAGE) and mean percent of readings within target glycemic range (>70-≤180 mg/dL) vs. PBO were improved. There was an increase in pts who reduced their A1c by ≥0.5% without severe hypoglycemia (odds ratios [95% CI]: 2.71 [1.81, 4.06] and 3.07 [2.05, 4.60] for DAPA 5 and 10 mg respectively). Hypoglycemic events, including severe hypoglycemia were balanced between treatment groups. There were more adjudicated definite diabetic ketoacidosis (DKA) events on DAPA.

 

In conclusion, DAPA vs. PBO as add-on to INS in pts with T1D was well tolerated, improved glycemic control and decreased variability without increasing hypoglycemia but with more DKA events.

 

Week 24 outcomes DAPA 5 mg + INS
(n=271) DAPA 10 mg + INS
(n=270) Placebo + INS
(n=272)
HbA1c, %
Mean (SD) at baseline
Wk 24 adjusted mean change from baseline (SE)
Difference vs PBO (95% CI)
p value .
8.45 (0.69)
−0.34 (0.05)
−0.37 (−0.49, −0.26)
<0.0001 .
8.39 (0.67)
−0.39 (0.05)
−0.42 (−0.53, −0.30)
<0.0001 .
8.40 (0.63)
0.03 (0.05)

TDD, IU, insulin doses
Mean (SD) at baseline
Wk 24 adjusted mean change from baseline (SE)
Difference vs PBO (95% CI)
p value .
59.09 (28.05)
−8.73 (1.22)
−10.78 (−13.73, −7.72)
<0.0001 .
59.28 (28.21)
−9.05 (1.23)
−11.08 (−14.04, −8.02)
<0.0001 .
56.45 (25.23)
2.29 (1.39)

Body weight, kg
Mean (SD) at baseline
Wk 24 adjusted mean change from baseline (SE)
Difference vs PBO (95% CI)
p value .
79.22 (17.21)
−3.22 (0.27)
−3.21 (−3.96, −2.45)
<0.0001 .
80.39 (18.51)
−3.76 (0.27)
−3.74 (−4.49, −2.99)
<0.0001 .
79.03 (19.05)
−0.02 (0.28)

24-h CGM glucose reading, mg/dL
Mean (SD) at baseline
Wk 24 adjusted mean change from baseline (SE)
Difference vs PBO (95% CI)
p value .
192.67 (28.68)
−6.46 (1.83)
−15.66 (−20.26, −11.05)
<0.0001 .
191.53 (28.09)
−10.54 (1.83)
−19.74 (−24.34, −15.14)
<0.0001 .
190.89 (28.95)
9.20 (1.85)

MAGE during 24-h CGM, mg/dL
Mean (SD) at baseline
Wk 24 adjusted mean change from baseline (SE)
Difference vs PBO (95% CI)
p value .
169.35 (29.60)
−10.17 (1.90)
−9.85 (−14.66, −5.03)
<0.0001 .
171.02 (29.85)
−9.68 (1.91)
−9.36 (−14.16, −4.55)
0.0001 .
168.38 (29.29)
−0.33 (1.93)

24-h interstitial glucose values within >70-≤180 mg/dL, %
Mean (SD) at baseline
Wk 24 adjusted mean change from baseline (SE)
Difference vs PBO (95% CI)
p value .
43.50 (12.43)
5.92 (0.82)
9.02 (6.97, 11.06)
<0.0001 .
43.68 (11.83)
7.60 (0.82)
10.70 (8.66, 12.74)
<0.0001 .
43.53 (12.55)
−3.10 (0.83)

Safety data (patients with an event)
≥1 AE, n (%)
≥1 SAE, n (%)
≥1 related SAE, n (%)
≥1 event of hypoglycemia, n (%)
≥1 event of severe hypoglycemia, n (%)
Definite DKA, n (%) .
197 (72.7)
18 (6.6)
13 (4.8)
223 (82.3)
17 (6.3)
7 (2.6) .
181 (67.0)
7 (2.6)
3 (1.1)
231 (85.6)
23 (8.5)
6 (2.2) .
172 (63.2)
5 (1.8)
2 (0.7)
234 (86.0)
21 (7.7)
0

 

Poster 213-OR

 

In summary, adding SGLT inhibitor dapagliflozin to intensive therapy in adults with T1DM who had suboptimal glycemic control reducered blood glucose levels, aided in weight loss, reduction in insulin doses, also correlated with a small increases in diab ketoacidosis risk compared to placebo (definite DKA 2.6 per cent versus 0 per cent)

 

DEPICT 2 was a phase 3 double blind global study in 137 sites in USA, South America, Europé and Asia. 

 

813 adults were enrolled in the study with HbA1c DCCT 7.5-10.5 per cent. 

 

HbA1c decreased by 4.0 mmol per mol. The insulin doses were reducered with 11 per cent. CGM showed more stable improved stable glycemic values leading to an increased time in range 2 h 10 min over 24 h. 

 

The study has been accepted for publikation in the upcoming issue of Diab Care

 

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