Add‐on therapy with dapagliflozin under full closed loop control improves time in range in adolescents and young adults with type 1 diabetes: The DAPADream study

Abstract

Aim To investigate the effect of the sodium‐glucose co‐transporter‐2 inhibitor dapagliflozin on glucose levels overnight and during the following day after two unannounced meals under full closed loop (FCL) conditions. Materials and Methods For this single‐centre, double‐blind, randomized, placebo‐controlled, cross‐over trial, non‐obese persons with type 1 diabetes (T1D) were studied twice (10 mg dapagliflozin bid vs. placebo) for 24 hours with two unannounced mixed meal tests 6 hours apart under FCL conditions. Primary outcome was sensor glucose time in range (TIR; 3.9‐10 mmol/L). For safety evaluation, ß‐hydroxybutyrate (BHB), glucagon, insulin and gastric inhibitory polypeptide were measured. Results Fifteen adolescents (aged 15.4 ± 1.6 years, diabetes duration 10.0 ± 3.4 years, HbA1c 8.4% ± 0.9% [67.7 ± 10.1 mmol/mol]) and 15 young adults (aged 18.7 ± 0.8 years; diabetes duration 12.5 ± 3.6 years; HbA1c 8.3% ± 0.9% [68.5 ± 11.2 mmol/mol]) completed the trial. TIR was significantly higher in the intervention group compared with placebo (68% ± 6% vs. 50% ± 13%; P < .001); nocturnal glucose was significantly lower with dapagliflozin (6.2 ± 0.7 vs. 7.3 ± 1.7 mmol/L; P = .003) without an increase in time at less than 3.9 mmol/L (3.3% ± 6.0% vs 3.1% ± 5.2%; P = .75). Urinary glucose excretion was increased 3‐fold using dapagliflozin (149 ± 42 vs. 49 ± 23 g/24 hours) with a total insulin reduction of 22% (39.7 ± 12.7 vs. 30.6 ± 10.4 U; P = .004). No abnormal elevated BHB values were observed. Conclusions In adolescents and adults with T1D, dapagliflozin significantly increased TIR on average by 259 minutes/day while reducing glycaemic variability during FCL control without any signs of hypoglycaemia or ketosis.

Sodium–glucose cotransporter 2 inhibitors as an add-on therapy to insulin for type 1 diabetes mellitus: Meta-analysis of randomized controlled trials

“…In a meta-analysis, SGLT2is ameliorated glycemic efficacy outcomes accompanied by a lower insulin dose requirement without increasing the risk of hypoglycemia [40]. Importantly, SGLT2is improving glycemic control by increasing time in range on average while reducing glycemic variability [41,42]. SGLT2is are particularly attractive for add-on therapy to insulin in T1DM because they are oral agents that decrease the reabsorption of glucose in the kidney and increase its excretion via the urine, a mechanism that is not dependent of islet cell functionality [14-16, 43, 44].…”

Strategically Playing with Fire: SGLT Inhibitors as Possible Adjunct to Closed-Loop Insulin Therapy

“…Two studies have used dapagliflozin and empagliflozin as adjunct to closed-loop therapy. 85,86 In the study described in Biester et al 85 dapagliflozin 10 mg BID (2 doses) was used as adjunct to fully closed-loop; participants were given 2 mixed meal tests 6 hours apart without meal announcement. The TIR with dapagliflozin was 68% compared to 50% in the placebo arm ( P < .001), and required 22% less insulin.…”

AID(„automated insulin delivery“)-Systeme in der Diabetologie

“…In einer kleinen Pilotstudie wurde versucht, zusätzlich zu einen kompletten "closed loop" den SGLT-2-Inhibitor (SGLT-2: "sodium dependent glucose transporter 2") Dapagliflozin zu verabreichen, um die Insulinwirkung um die renale Glukoseexkretion zu erweitern. Zwar erhöht sich mit Dapagliflozin die Zeit im Zielbereich, und die Auslenkung der Spiegel ist nicht ganz so hoch, aber hohe postprandiale Werte sind immer noch vorhanden [21].…”