Efficacy and Safety Analysis of Insulin Degludec/Insulin Aspart (IDegAsp) Compared with Biphasic Insulin Aspart 30 (BIAsp 30 [NovoLog® Mix 70/30]): A Phase 3, Multicenter, International, Open-Label, Randomized, Treat-to-Target Trial in Patients with Type 2 Diabetes Fasting during Ramadan
Presentation Number: LB SUN 77
Date of Presentation: April 2nd, 2017
Mohamed Hassanein*1, Akram Echtay2, Rachid Malek3, Mahommed Omar4, Shehla Sajid Shaikh5, Edmond Gabriel Fita6, Kadriye Kaplan6 and Nor Azmi Kamaruddin7
1Dubai Hospital, Dubai, United Arab Emirates, 2Rafic Hariri University Hospital, Beirut, Lebanon, 3CHU SETIF, Setif, Algeria, 4University of KwaZulu Natal, Durban, South Africa, 5Prince Aly Khan Hospital, Mumbai, India, 6Novo Nordisk A/S, Søborg, Denmark, 7National University of Malaysia, Kuala Lumpur, Malaysia
While Muslims with serious medical conditions, including some people with diabetes, are exempt from Ramadan fasting (no food or drink from dawn to sunset), many continue to fast. This intermittent fasting puts patients at high risk of developing dehydration, hypoglycemia and overt hyperglycemia. Due to this concern, patient recruitment for clinical trials taking place during Ramadan is challenging and trials on insulin use during Ramadan are scarce. IDegAsp, a new co-formulation of insulin degludec and insulin aspart is associated with a reduced risk of hypoglycemia compared with BIAsp 30 (NovoLog® Mix 70/30) due to the flat pharmacokinetic profile and long duration of action of insulin degludec. This international, randomized, treat-to-target trial is the first to compare the efficacy and safety of two insulin analogues (IDegAsp and BIAsp 30) during Ramadan in countries with a large Muslim population.
Patients with type 2 diabetes (T2D) who intended to fast and were on basal, pre-mixed or self-mixed insulin ± oral antidiabetic drugs for ≥90 days, were randomized (1:1) to IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment duration was up to 28 weeks (treatment initiation, 8–20 weeks pre-Ramadan; Ramadan, 4 weeks; post-Ramadan, 4 weeks). Insulin doses were titrated to achieve a plasma glucose (PG) target of 4–5 mmol/L during the initiation period and 5–7 mmol/L during Ramadan. At the start of Ramadan, a 30–50% reduction of one of the two doses of both insulins was recommended. Hypoglycemia was recorded as severe (requiring third-party assistance), nocturnal (any hypoglycemia occurring 00:01–05:59) or overall (severe or PG <3.1 mmol/L [56 mg/dL]).
In total, 263 patients were randomized to IDegAsp (n=131) or BIAsp 30 (n=132). IDegAsp was non-inferior to BIAsp 30 in HbA1creduction from baseline to end of Ramadan. During the 28-week treatment period, rates of overall and nocturnal hypoglycemia, respectively, were 74% and 83% lower with IDegAsp vs. BIAsp 30. The rates of severe hypoglycemia per 100 patient years of exposure were 8.33 with IDegAsp and 16.33 with BIAsp 30.
During the month of Ramadan, there was a 62% lower rate of overall hypoglycemia with IDegAsp vs. BIAsp 30; rate ratio (RR) 0.38 (95% CI: 0.19; 0.77). The rate of nocturnal hypoglycemia was 74% lower with IDegAsp vs. BIAsp 30; RR 0.26 (95% CI: 0.08; 0.88).
In conclusion, this trial in a high-risk population of patients with T2D fasting during Ramadan showed similar efficacy of IDegAsp and BIAsp 30 in controlling blood glucose during and after Ramadan. IDegAsp, however, was associated with lower rates of overall and nocturnal hypoglycemia vs. BIAsp 30.
Trial Registration: NCT02648217
Disclosure: MH: Consultant, Novo Nordisk, Consultant, Eli Lilly, Consultant, Sanofi, Consultant, Novartis, Consultant, MSD. AE: Speaker, Novo Nordisk, Speaker, Sanofi, Speaker, Astra Zeneca, Speaker, MSD, Speaker, Lilly, Speaker, Boehringer, Speaker, Merck, Speaker, Novartis, Principal Investigator, Novo Nordisk, Principal Investigator, MSD, Principal Investigator, Sanofi, Principal Investigator, Merck, Principal Investigator, Boehringer, Principal Investigator, Astra Zeneca, Principal Investigator, Novartis. MO: Advisory Group Member, Eli Lilly & Company, Speaker Bureau Member, Eli Lilly & Company, Speaker Bureau Member, Sanofi Aventis, Speaker Bureau Member, LifeScan, Advisory Group Member, Novo Nordisk, Speaker Bureau Member, Novo Nordisk. EGF: Employee, Novo Nordisk, Employee, Novo Nordisk. KK: Employee, Novo Nordisk, Employee, Novo Nordisk. NAK: Advisory Group Member, Novo Nordisk, Study Investigator, Novo Nordisk. Nothing to Disclose: RM, SSS