Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA-Ramadan): a randomized trial

• Published in: Diabetes, obesity & metabolism Vol. 18; no. 10; pp. 1025 - 1033
• Main Authors: Azar, S. T., Echtay, A., Wan Bebakar, W. M., Al Araj, S., Berrah, A., Omar, M., Mutha, A., Tornøe, K., Kaltoft, M. S., Shehadeh, N.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01-10-2016; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; Antidiabetics; Body mass index; Body weight; Diabetes; Diabetes mellitus (non-insulin dependent); Diabetes Mellitus, Type 2 - blood; Diabetes Mellitus, Type 2 - drug therapy; Drug Substitution - methods; Drug Therapy, Combination; Fasting; Fasting - metabolism; Female; fructosamine; GLP-1; Hemoglobin; Humans; hypoglycaemia; Hypoglycemic Agents - administration & dosage; Hypoglycemic Agents - adverse effects; Islam; liraglutide; Liraglutide - administration & dosage; Liraglutide - adverse effects; Male; Metformin; Metformin - administration & dosage; Metformin - adverse effects; Middle Aged; Original; Ramadan; Sulfonylurea Compounds - administration & dosage; Sulfonylurea Compounds - adverse effects; sulphonylurea; Treatment Outcome; type 2 diabetes; body weight; liraglutide; GLP-1; type 2 diabetes; sulphonylurea; hypoglycaemia; metformin; fasting; Ramadan; fructosamine
• ISSN: 1462-8902; 1463-1326
• DOI: 10.1111/dom.12733

Aims
Compare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan.
Materials and methods
In this up to 33‐week, open‐label, active‐controlled, parallel‐group trial, adults [glycated haemoglobin (HbA1c) 7%‐10% (53‐86 mmol/mol); body mass index ≥20 kg/m2; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once‐daily liraglutide (final dose 1.8 mg) or continue pre‐trial sulphonylurea at maximum tolerated dose, both with metformin. Primary endpoint: change in fructosamine, a validated marker of short‐term glycaemic control, during Ramadan.
Results
Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (−12.8 µmol/L); sulphonylurea (−16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: −5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide‐treated (2%, three subjects) versus sulphonylurea‐treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: −0.54 kg; 95% CI: −0.94;−0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: −0.59% (−6.40 mmol/mol), 95% CI: −0.79; −0.38%; −8.63; −4.17 mmol/mol; p < 0.0001].
Conclusions
Despite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA‐Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting.