Adding the SGLT2 inhibitor Dapagliflozin in type 1 diabetes treatment helps lower HbA1c and decrease variability in glucose ranges.
Sodium glucose cotransporter 2 inhibitors are insulin-independent antihyperglycemic medications used for therapy in people who have type 2 diabetes. However, they have potential use for adjunct therapy with insulin in people who have type 1 diabetes because they have the additional benefits of weight loss and better glycemic stability.
The DEPICT-2 study was conducted to investigate the efficacy and safety of dapagliflozin as adjunct therapy to insulin alone. This was a double-blind, randomized, parallel-controlled, three-arm, phase 3 study. This study took patients from 148 different sites and many different countries. Patients enrolled were adults who have type 1 diabetes with an HbA1c (7.7-11%) and receiving adjustable insulin multiple times a day or insulin infusions for more than one year prior to enrolling. Patients were than randomly assigned either dapagliflozin 5 mg, 10 mg, or placebo, and instructed to take it daily. The study lasted 24 weeks.
The primary outcome was change in HbA1c. Secondary outcomes included changes in total daily insulin dose, changes in body weight, masked continuous glucose monitoring (CGM) end points, and changes in 24-hour readings. A total of 815 patients were enrolled and assigned to either dapagliflozin 10 mg, 5 mg, or placebo. The mean baseline HbA1c was 8.43%, mean baseline body weight was 79.2 kg, and mean baseline BMI was 27.6kg/m2. The mean TDD at baseline was 57.81 IU, with 537 patients (66.1%) using MDI and 276 (33.9%) using CSII; 258 patients were using CGM at baseline.
Results showed mean changes (95% CI) in HbA1c from baseline to week 24 versus placebo were 20.37% (P,0.0001) and 20.42% (P, 0.0001) for dapagliﬂozin 5 mg and 10 mg, respectively. The initial reduction in HbA1c took place in the ﬁrst four weeks and the effect was maintained throughout the study. Body weight was also reduced significantly in the treatment groups. Mean percent change in TDD for the duration of 24 weeks for dapagliﬂozin 5 mg and 10 mg versus placebo was 210.78% and 211.08%, respectively. Reductions in TDD occurred in the ﬁrst two weeks of treatment and were maintained throughout the study. The time patients spent in the target glycemic range was significantly improved. More than 50% of the continuous glucose monitoring readings were in the target range by week 24 in both dapagliflozin groups.
When looking at the safety of dapagliflozin in type 1 treatment, all three groups had similar percentages of adverse events and all events were considered mild to moderate intensity. A similar number of patients reported hypoglycemia in all three groups. Diabetic ketoacidosis occurrence rates were 2.6%, 2.2%, and 0% for dapagliflozin 5 mg, 10 mg, and placebo, respectively.
Dapagliflozin does help lower HbA1c and is well tolerated as adjunct therapy for adults who have type 1 diabetes. There was no increase in adverse events or hypoglycemia, however there was a higher incidence of diabetic ketoacidosis. In a patient with type 1 diabetes who has elevated glucose levels, dapagliflozin is a relatively safe and effective option.
- In adults who have type 1 diabetes and hyperglycemia, dapagliflozin is an effective adjunct therapy option.
- Dapagliflozin did not increase hypoglycemic events but did increase DKA incidences.
- Adding an SGLT2 inhibitor like dapagliflozin can help adults who have type 1 diabetes stay in target blood glucose range, which improves their overall health and limits complications associated hyperglycemia.
Chantal Mathieu, Paresh Dandona, Pieter Gillard, Peter Senior, Christoph Hasslacher, Eiichi Araki, Marcus Lind, Stephen C. Bain, Serge Jabbour, Niki Arya, Lars Hansen, Fredrik Thorén, Anna Maria Langkilde. Efficacy and Safety of Dapagliflozin in Patients With Inadequately Controlled Type 1 Diabetes (the DEPICT-2 Study): 24-Week Results From a Randomized Controlled Trial. (2018) 41 (9) 1938-1946; DOI: 10.2337/dc18-0623
Angela Reyes, Pharm.D. Candidate, LECOM College of Pharmacy