Treatment Intensification with Insulin Degludec/Insulin Aspart Twice Daily: Randomized Study to Compare Simple and Step-Wise Titration Algorithms

Abstract

This 26-week, multicenter, randomized, open-label, parallel-group, treat-to-target trial in adults with type 2 diabetes compared the efficacy and safety of treatment intensification algorithms with twice-daily (BID) insulin degludec/insulin aspart (IDegAsp). Patients randomized 1:1 to IDegAsp BID used either a 'Simple' algorithm (twice-weekly dose adjustments based on a single prebreakfast and pre-evening meal self-monitored plasma glucose [SMPG] measurement; IDegAsp[BIDSimple], n = 136) or a 'Stepwise' algorithm (once-weekly dose adjustments based on the lowest of 3 pre-breakfast and 3 pre-evening meal SMPG values; IDegAsp[BIDStep-wise], n = 136). After 26 weeks, mean change from baseline in glycated hemoglobin (HbA1c) with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise] (-15 mmol/mol versus -14 mmol/mol; 95% confidence interval [CI] upper limit, <4 mmol/mol) (baseline HbA1c: 66.3 mmol/mol IDegAsp[BIDSimple] and 66.6 mmol/mol IDegAsp[BIDStep-wise]). The proportion of patients who achieved HbA1c <7.0% (<53 mmol/mol) at the end of the trial was 66.9% with IDegAsp[BIDSimple] and 62.5% with IDegAsp[BIDStep-wise]. Fasting plasma glucose levels were reduced with each titration algorithm (-1.51 mmol/L IDegAsp[BIDSimple] versus -1.95 mmol/L IDegAsp[BIDStep-wise]). Weight gain was 3.8 kg IDegAsp[BIDSimple] versus 2.6 kg IDegAsp[BIDStep-wise], and rates of overall confirmed hypoglycemia (5.16 episodes per patient-year of exposure [PYE] versus 8.93 PYE) and nocturnal confirmed hypoglycemia (0.78 PYE versus 1.33 PYE) were significantly lower with IDegAsp[BIDStep-wise] versus IDegAsp[BIDSimple]. There were no significant differences in insulin dose increments between groups. Treatment intensification with IDegAsp[BIDSimple] was noninferior to IDegAsp[BIDStep-wise]. Both titration algorithms were well tolerated; however, the more conservative step-wise algorithm led to less weight gain and fewer hypoglycemic episodes. Clinicaltrials.gov: NCT01680341.