Exclusion criteria included: thiazolidinedione or glucagon-like-peptide-1 treatment within the 3 months before the study; cardiac disease within the last 6 months (defined as decompensated heart failure New York Heart Association class III or IV); unstable angina pectoris; myocardial infarction; severe hypertension (systolic blood pressure ≥180 mmHg or diastolic blood pressure ≥100 mmHg); change in dose of any systemic treatment with products which, in the investigator’s opinion, could interfere

with glucose metabolism; clinically significant diseases which, in the investigator’s opinion, may confound see more the results of the trial or pose additional risk in administering trial product(s); impaired hepatic function (aspartate aminotransferase or alanine aminotransferase >2.5 times upper normal range); impaired renal function (serum creatinine levels ≥133 μmol/L [males], ≥124 μmol/L

[females] or estimated creatinine clearance below 60 mL/min). Withdrawal was at the discretion of the investigator or if non-compliance was reported. All participants receiving BIAsp 30 had their insulin dose titrated by the investigator in accordance with titration guidelines [12]. Starting dose for BIAsp 30 was 6 U pre-breakfast and 6 U pre-dinner in the BID groups, and 12 U pre-dinner in the QD group. The BIAsp 30 dose was adjusted according to SMPG measurements taken on any 3 days in the week prior to a site visit/phone contact. This was conducted weekly for the first 6 weeks, and every second week thereafter. BIAsp 30 dose was adjusted by –2 U if pre-meal SMPG was <4.4 mmol/L, Caspase inhibitor 0 U if 4.4–6.1 mmol/L, +2 U if 6.2–7.8 mmol/L, +4 U if 7.9–10 mmol/L and +6 U if >10 mmol/L. All participants received a stable dose of metformin 1000 mg/day. In the BIAsp 30 + sitagliptin arms, the dose of sitagliptin was 100 mg/day. The primary cAMP endpoint was change from baseline in HbA1c after 24 weeks of treatment. Secondary efficacy

endpoints included the proportion of subjects achieving HbA1c <7.0%, and the proportion achieving HbA1c <7.0% without hypoglycaemia (any symptomatic hypoglycaemia with a plasma glucose value ≤3.9 mmol/L or any single plasma glucose value <3.1 mmol/L in the last 3 months of treatment), change from baseline in fasting plasma glucose (FPG), total daily insulin dose and 7-point self-measured capillary SMPG profiles. Safety endpoints included adverse events (AEs), changes from baseline in bodyweight, daytime and nocturnal treatment-emergent hypoglycaemic episodes, physical examination, vital signs, and changes in haematology and biochemistry measurements. Laboratory analyses were performed by a central laboratory. Confirmed hypoglycaemia was defined post hoc and comprised all episodes with a plasma glucose measurement <3.1 mmol/L (regardless of symptoms) and any episodes considered severe (requiring third-party assistance). Nocturnal hypoglycaemia was deemed to occur if the episode took place between 00:01 and 05:59 h (inclusive).