A 32-Week Randomized Comparison of Stepwise Insulin Intensification of Biphasic Insulin Aspart (BIAsp 30) Versus Basal–Bolus Therapy in Insulin-Naïve Patients with Type 2 Diabetes

Abstract

IntroductionThis 32-week, open-label, randomized, parallel-group, multinational trial aimed to compare the efficacy and safety of stepwise insulin intensification of biphasic insulin aspart 30 (BIAsp 30) relative to stepwise intensification of a basal–bolus regimen in insulin-naïve adults with type 2 diabetes (T2D) who continued pretrial treatment with metformin and sulfonylurea.MethodsAdults with T2D were randomized into one of two treatment arms for 32 weeks: (1) BIAsp 30 once daily (OD), with the possibility of stepwise treatment intensification up to BIAsp 30 three times daily (TID); (2) insulin glargine OD, with the possibility of stepwise treatment intensification with insulin aspart up to TID. The primary endpoint was change from baseline in HbA1c after 32 weeks.ResultsAfter 32 weeks, the estimated mean change in HbA1c from baseline was statistically significantly lower in the BIAsp 30 arm (− 1.18%) versus basal–bolus (− 1.36%) [estimated treatment difference 0.18%; 95% confidence interval (95% CI) 0.01; 0.36; p < 0.05]. The proportion of patients with HbA1c below 7.0% was statistically significantly lower with BIAsp 30 (42.9%) compared with basal–bolus (56.9%) (odds ratio 0.58; 95% CI 0.37; 0.89; p = 0.01). The overall rate of severe or blood glucose (BG)-confirmed hypoglycemic events was numerically lower for BIAsp 30 compared with basal–bolus, and a statistically significantly lower rate in nocturnal severe or BG-confirmed hypoglycemia in the BIAsp 30 arm relative to basal–bolus was observed: estimated rate ratio 0.32 (95% CI 0.13; 0.79), p = 0.0131. The proportion of patients with adverse events was similar in both treatment arms.ConclusionInsulin intensification with BIAsp 30 and basal–bolus showed an improvement in glycemic control; the change in HbA1c was statistically significantly lower for BIAsp 30 compared to basal–bolus. Basal–bolus treatment was accompanied by a numerically, and statistically significantly, higher rate of overall and nocturnal severe or BG-confirmed hypoglycemia, respectively, compared with BIAsp 30.FundingNovo Nordisk A/S.Trial RegistrationClinicalTrials.gov identifier, NCT02453685.

Efficacy and Safety of Basal Analog Regimens in Type 2 Diabetes Mellitus: Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…A total of 9691 patients were included in the analysis. The most common BA insulin treatments were insulin glargine 100 U/mL (19 studies: [ 2 , 13 – 15 , 17 – 24 , 26 – 32 ]) and insulin aspart (11 studies: [ 15 , 16 , 18 – 20 , 22 , 23 , 25 , 31 – 33 ]). The patient characteristics in each trial are also reported in Table 1 .…”

“…There was generally a low risk of selection bias across the studies, with some studies judged as having an unclear risk of such bias. In eight studies [ 13 , 16 , 18 , 20 , 25 , 28 , 32 , 33 ], inadequate methods of generating the randomization sequence were reported; similarly, seven studies were judged to have an unclear risk of allocation concealment due to insufficient details [ 2 , 13 , 15 , 16 , 28 , 32 , 33 ]. Risk of performance bias (pertaining to the blinding of participants and personnel) and risk of detection bias (pertaining to blinding of outcome assessment) were primarily judged to be high, as most of the studies had an open-label study design.…”

Diabetic Gastroparesis

“…The comprehensive review by Krishnasamy and Abell describes diabetic gastroparesis in detail [ 6 ]. Defined as delayed gastric emptying with associated upper gastrointestinal symptoms in the absence of any mechanical obstruction [ 7 ], diabetic gastroparesis may present with a variety of symptoms.…”

“…The long list of complaints is accompanied by an equally exhaustive list of differential diagnoses, including iatrogenic or drug-induced delay in gastric emptying. Diabetic gastroparesis is accoutered by poor glucose control, suboptimal nutritional and hydration status, greater risk of CVD, hypertension and retinopathy, frequent need for hospitalization, and poor quality of life [ 6 ]. Thus, diabetic gastroparesis is not only a marker of poor current control but also a predictor of poor future outcomes.…”

“…The management strategy of diabetic gastroparesis is multifactorial. A careful drug history must be taken to exclude prescription, over the counter, and alternative medicine drugs, as well as nutritional supplements which may worsen gastric motility [ 6 ]. In particular, the need for prescribing proton pump inhibitors or H2 receptor blockers must be reassessed in a person with gastroparesis.…”