AIMS: To determine the effectiveness and safety of early combination therapy with insulin degludec and intravenous insulin infusion (IVII) compared with IVII alone in diabetic ketoacidosis (DKA) management.
MATERIALS AND METHODS: This prospective, open-label, randomised controlled trial included 80 adults (=18 years) with DKA. Participants were randomised to either the intervention group, which received early subcutaneous (SC) insulin degludec (0.3 units/kg SC within 3 h of diagnosis) plus standard IVII, or the control group, which received standard IVII alone. The primary outcome was time to DKA resolution. Secondary outcomes included rebound hyperglycaemia, rebound DKA, hypoglycaemia, hypokalaemia, length of hospital stay (LOS), and in-hospital mortality.
RESULTS: Eighty patients were enrolled; 67.5% of participants had type 2 diabetes. Baseline characteristics were comparable between groups. DKA resolution was significantly faster in the early degludec group by 3.25 h (7.75 h, IQR 6.00-9.00 h vs. 11.00 h, IQR 6.25-15.00; p = 0.039). At 72 h after transition to SC insulin, mean capillary blood glucose (CBG) was significantly lower with early degludec (213.9 ± 25.8 mg/dL vs. 240.1 ± 42.0 mg/dL; p = 0.012). Rates of rebound hyperglycaemia at 12 h after bridging, mean CBG levels at 12, 24, and 48 h among those with rebound hyperglycaemia, as well as rates of rebound DKA, hypoglycaemia, hypokalaemia, LOS, and in-hospital mortality, were not significantly different between groups.
CONCLUSIONS: Early administration of SC insulin degludec in combination with IVII accelerated DKA resolution and improved blood glucose levels at 72 h in patients with rebound hyperglycaemia after discontinuation of IVII, without increasing the risk of hypoglycaemia or hypokalaemia.
| Discipline Area | Score |
|---|---|
| Hospital Doctor/Hospitalists |  |
| Internal Medicine | |
| Endocrine | |
| Emergency Medicine |  |
The control arm did not appear to receive any long-acting insulin, so the intervention was not compared with recommended practice (in the UK, at least). The findings, therefore, provide some evidence to support current practice of prescribing long-acting insulin alongside IVII rather than changing practice.
This RCT evaluated insulin degludec in managing adult patients with DKA. Patients were randomized to early subcutaneous degludec plus standard IV insulin infusion compared with IV insulin infusion alone. The primary outcome was time to DKA resolution. 80 patients were included and DKA resolution was faster in the early degludec group by 3.25 h (7.75 h, IQR 6.00–9.00 h vs 11.00 h, IQR 6.25–15.00). At 72 h after transition to SC insulin, mean capillary blood glucose was significantly lower with early degludec. There are several limitations, including the unblinded design, and ketone concentrations were not routinely monitored or used to determine <250 mg/dL at diagnosis. Despite these issues, this study demonstrates utility of insulin degludec in managing DKA with faster time to resolution, improved blood glucose levels, and less rebound hyperglycemia.
This open-label RCT compared the use (or not) of degludec early on in treating diabetic ketoacidosis (DKA) as an add-on to intravenous insulin. The population is unusual in that two thirds had type 2 diabetes. The study showed a quicker resolution of DKA with early subcutaneous long-acting degludec (and a higher total insulin dose delivered) without an increase in complications.