Adding the selective SGLT2* inhibitor dapagliflozin to insulin therapy improves HbA1c levels in patients with inadequately controlled type 1 diabetes (T1D), according to the DEPICT-2** study presented at ADA 2018.
“The results of our study add to a growing body of evidence showing that SGLT2 inhibitors have the potential to serve as promising adjunct therapies in people with T1D who are not consistently in their target blood glucose range,” said lead author Professor Chantal Mathieu from the Catholic University of Leuven, Leuven, Belgium.
This phase III, double-blind trial involved 813 patients (median age 42 years, 60 percent female, mean BMI 27 kg/m2) with T1D (HbA1c level of ≥7.5 percent to ≤10.5 percent) from North and Latin America, Europe, and Japan. Patients were randomized in a 1:1:1 ratio to receive dapagliflozin 5 mg (n=271), dapagliflozin 10 mg (n=270), or placebo (n=272) as an add-on to insulin for a 24-week treatment period. [ADA 2018, abstract 213-OR]
Compared with patients on placebo, dapagliflozin-treated patients had a significantly greater reduction in HbA1c levels from baseline (difference from baseline, -0.34 percent and -0.39 percent for 5 mg and 10 mg, respectively vs 0.03 percent) at 24 weeks of follow-up.
Patients on dapagliflozin 5 mg and 10 mg also showed significant reduction from baseline in total daily insulin dose required compared with those on placebo (difference from baseline, -8.73 percent and -9.05 percent, respectively vs 2.29 percent). These results were comparable to the previous DEPICT-1 study, except that in this study, there was no dose difference in insulin reduction at 24 weeks, said Mathieu.
Additionally, there was a -3.21 percent and -3.74 percent reduction in body weight in the dapagliflozin treatment arm compared with the placebo arm (P<0.0001 for both 5 mg and 10 mg dapagliflozin).
The researchers highlighted that the percentage of patients who reached ≥0.5 percent reduction inHbA1c without having severe hypoglycaemia was more than doubled in the dapagliflozin group compared with the placebo group (39.5 percent vs 20.1 percent, odds ratio [OR], 2.71 for 5 mg and 41.6 percent vs 20.1 percent, OR, 3.07 for 10 mg).
Although the overall adverse events were balanced between treatment groups, a higher incidence of diabetic ketoacidosis (DKA) was observed among patients on dapagliflozin 5 mg and 10 mgcompared with patients on placebo (n=7 and n=6 vs n=0). “[These are] low number of patients, but still there was an imbalance,” Mathieu noted, adding that the team is pulling together all cases described in DEPICT-1 and DEPICT-2 studies to establish a pattern in the DKA events.
“In the DEPICT-1 study, we did not have this imbalance, mainly because of the presence of DKA in the placebo arm; whereas in our DEPICT-2 study, there were no [DKA] events in the placebo arm,” Mathieu said. “[It might be] very hard to find a pattern … [but we could look] at the 52-week data of the DEPICT-2 study to try and find a pattern in these [DKA] events.”
“Results of the DEPICT-2 study were consistent with those of its twin study, DEPICT-1, which followed mostly European and American patients with T1D. This new study had a greater global reach, with about a quarter of patients being from Asia [such as Japan]. The benefits seen in both studies are important to people with T1D. Introduction of dapagliflozin as an adjunct therapy could be an interesting and exciting new treatment for T1D, almost 100 years after the discovery of life-saving insulin. However, adding dapagliflozin to the insulin regimen needs to be balanced against the increased risk of DKA, and this therapy should be coupled with intensive educational measures to cope with the small, but real risks,”Mathieu said.
“[Furthermore,] placebo did not change during the study, but the two doses of dapagliflozin led to the lowering of HbA1c[level] that was highly statistically significant compared with placebo,” she added.
*SGLT2: Sodium-glucose cotransporter-2
**DEPICT: Dapagliflozin evaluation in patients with inadequately controlled type 1 diabetes
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