Dapagliflozin Shows Appropriate Safety in Real-World Type 1 Diabetes Study

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In the Dapa-ON trial, the careful selection of people with T1D and the implementation of strategies to reduce the risk of DKA were associated with dapagliflozin's appropriate safety profile.

Real-world dapagliflozin use showed an appropriate safety profile and clinical improvements among people living with type 1 diabetes (T1D) participating in the Dapa-ON multicenter retrospective study.1

Among 250 people with T1D included across 12 centers in Spain, a team of investigators measured the number of diabetic ketoacidosis (DKA) events over a 12-month follow-up period. Results from Dapa-ON reported a small number of DKA events after dapagliflozin initiation, showing similar or lower results compared with the estimated prevalence of DKA in the global population with T1D.

“Given that most participants in this study received dapagliflozin on-label, the lower event rate observed in our cohort may be explained by the awareness of this potential risk, and the subsequent implementation of strategies to avoid this complication, together with the careful selection of candidates for this treatment by experienced diabetologists” wrote the investigative team, led by José Ignacio Martínez-Montoro, of the department of endocrinology and nutrition, Virgen de la Victoria University Hospital.

A mainstay of treatment for T1D, intensive insulin therapy aims to achieve optimal glycemic control in order to reduce the risk of diabetes-associated adverse complications. Despite innovations in the diabetes management space, however, many people living with T1D do not achieve glycemic targets and experience significant disease-related burdens. The onset of the sodium-glucose cotransporter 2 (SGLT2) inhibitor medication class, as an adjunct to insulin therapy, has improved glycemic control and weight loss in T1D, with additional benefits observed in those with chronic kidney disease or heart failure, regardless of diabetes status.2

However, safety concerns related to SGLT2 inhibitor use have been identified, particularly an increased risk of DKA associated with dapagliflozin use in people with T1D. Martínez-Montoro and colleagues noted that careful selection of appropriate patients for SGLT2 inhibitor use and the implementation of strategies to reduce DKA could lower the risk of the complication, despite limited real-world evidence.1

In their analysis, the investigative team assessed the 12-month safety and effectiveness of dapagliflozin as an adjunctive therapy to insulin in people living with T1D. The team reviewed the electronic medical records at 12 centers in Spain and obtained clinical, anthropometric, and biochemical data at the time of dapagliflozin prescription and 6- and 12-month post-initiation.

Among the 250 people living with T1D included in the analysis, 82.4% were on multiple daily injection therapy (MDI) and 80.8% were treated with on-label dapagliflozin. Among the 207 participants who completed the 12-month follow-up period, investigators observed 5 cases of DKA (2.4% [95% CI, 0.3 - 4.5]). According to the analysis, the contributing factors include insulin pump malfunction (n = 2), concomitant illness (n = 2), and insulin dose omission (n = 1).

Martínez-Montoro and colleagues indicated DKA events were observed more frequently among insulin pump users (7.7% versus 1.2%). Notably, 4 of the reported DKA events occurred within the first 6 months after dapagliflozin initiation. There were no deaths or persistent sequelae due to DKA reported in the data, as well as no episodes of severe hypoglycemia.

Further analysis revealed significant reductions in mean body weight (3.3 kg; weight mean difference, -3.9%), as well as significant improvements in total HbA1c (-0.6%), and total daily insulin dose (-8.6%), at 12 months after dapagliflozin initiation (all P <.001). A subgroup with available continuous glucose monitoring (CGM) metric data showed significant improvements in time-in-range (+9.3%), time-above-range (-7.2%), time-below-range (-2.5%), and glucose variability (coefficient of variation, -5.1%) 12 months after dapagliflozin initiation.

Martínez-Montoro and colleagues noted these CGM metrics are not commonly evaluated in the literature related to the use of SGLT2 inhibitors in people with T1D and could highlight its clinical benefit. They suggested indicated SGLT2 inhibitor use may be considered for the understood cardiovascular and renal benefits, particularly independent of glycemic control, for people with T1D, but more research is necessary.

“However, dedicated studies evaluating the potential cardiovascular and renal benefits of SGLT2 inhibitors in people living with T1D are needed to confirm these findings, and support its use,” Martínez-Montoro and colleagues concluded.


  1. Durán-Martínez M, Azriel-Mira S, Doulatram-Gamgaram VK, et al. Real-world safety and effectiveness of dapagliflozin in people living with type 1 diabetes in Spain: The Dapa-ON multicenter retrospective study. Diabetes Metab. Published online December 5, 2023. doi:10.1016/j.diabet.2023.101501
  2. Stougaard EB, Rossing P, Cherney D, Vistisen D, Persson F. Sodium-glucose cotransporter 2 inhibitors as adjunct therapy for type 1 diabetes and the benefit on cardiovascular and renal disease evaluated by Steno risk engines. J Diabetes Complications. 2022;36(8):108257. doi:10.1016/j.jdiacomp.2022.108257