Real-world Evidence of Efficacy and Safety of SGLT2 Inhibitors as Adjunctive Therapy in Adults With Type 1 Diabetes: A European Two-Center Experience

Abstract

OBJECTIVE To evaluate real-world efficacy and safety of sodium–glucose cotransporter 2 inhibitor (SGLT2i) use in combination with insulin in people with type 1 diabetes. RESEARCH DESIGN AND METHODS We conducted a retrospective cohort European two-center study. Data on demographics, HbA1c, weight, insulin use, renal function, and adverse events were collected for 199 adults with type 1 diabetes who initiated a SGLT2i adjunct to insulin. Subgroup analyses were performed to identify who benefited most and who was more at risk for adverse events. RESULTS Overall, significant reductions in mean HbA1c (−0.5%), weight (−2.9 kg), and daily insulin (−8.5%) were achieved after 12 months. The greatest reduction in HbA1c was obtained in individuals with baseline HbA1c >8% (−0.7% [64 mmol/mol]). The most weight loss was observed in subjects with BMI >27 kg/m2 (−3.5 kg). Individuals with baseline estimated glomerular filtration rate (eGFR) <90 mL/min/1.73 m2 showed an increase in eGFR (4.5 mL/min/1.73 m2), whereas those with urinary albumin-to-creatinine ratio (UACR) >15 mg/g showed a decrease in UACR (−16.6 mg/g). Fifty-seven individuals (28.6%) reported adverse events: 45 with genital infections (22.6%), 5 ketosis episodes (2.5%), and 7 diabetic ketoacidosis (DKA) (3.5%). No severe hypoglycemia events were reported. CONCLUSIONS Our real-world data on SGLT2i showed promising results in reductions in HbA1c, weight, and insulin requirements in type 1 diabetes. Benefits were more pronounced in individuals with higher baseline HbA1c and BMI. DKA remained a major concern, despite educational measures. Further real-life evidence is still required for evaluation of SGLT2i longer-term effects and their impact on reno-cardiovascular outcomes.

Empagliflozin-Metformin Combination Has Antioxidative and Anti-Inflammatory Properties that Correlate with Vascular Protection in Adults with Type 1 Diabetes

“…This treatment is, in type 2 diabetes, safe and simple, thus allowing for it to be prescribed in different clinical settings. However, despite their high efficiency, the risks associated with the use of SGLT-2 inhibitors in individuals with type 1 diabetes should be also borne in mind [ 29 ]. In our study, blood ketones were carefully monitored throughout, with values not reaching the levels of detection.…”

“…In our study, blood ketones were carefully monitored throughout, with values not reaching the levels of detection. Under nonstudy conditions or in regular clinical practice, the risk of diabetic ketoacidosis exists; therefore, the prescription of SGLT-2 inhibitors in individuals with type 1 diabetes is not particularly advised [ 29 ].…”

From Skepticism to Hope: The Evolving Concept of the Initiation and Use of Sodium-Glucose Cotransporter 2 Inhibitors in Hospitalized Patients

“…In these studies, the safety profile supported a favorable risk–benefit balance. However, real-world evidence suggested that DKA remains a concern with the use of SGLT2i in autoimmune diabetes [ 38 ]. The recent withdrawal of dapagliflozin as an adjunctive therapy in T1D added to the concerns, although this was a commercial decision and not done for safety reasons [ 39 ].…”

Sodium, Glucose and Dysregulated Glucagon Secretion: The Potential of Sodium Glucose Transporters

“…A recent comparative retrospective cohort study assessed the use of different SGLT inhibitors and doses on blood glucose of patients with type 1 diabetes and found reduced insulin needs in treated groups. However, glucagon levels were not quantified in the study and therefore, in this setting, the effect on alpha cell function remains unclear ( Palanca et al, 2022 ). Nonetheless, double-blinded studies using inhibitors targeting SGLT1 over SGLT2 will be needed to fully understand the therapeutic potential.…”