Safety and efficacy of liraglutide 1.2mg in patients with mild and moderate renal impairment: the ABCD nationwide liraglutide audit

Abstract

Liraglutide is not predominantly eliminated by renal excretion. We assessed its safety and efficacy among patients with mild and moderate renal impairment.Patients from a nationwide audit of liraglutide (1.2mg) use were divided according to pre-treatment renal function calculated by the Cockcroft-Gault formula. Adverse events, liraglutide discontinuation and changes in HbA1c, weight, systolic blood pressure and serum creatinine were compared between groups of different pre-treatment renal function.As compared with patients with normal renal function (n=1446), patients with mild renal impairment (n=288) and moderate renal impairment (n=57) were equally likely to report gastrointestinal side effects (adjusted OR 1.11 [95% CI 0.80-1.54] and 0.67 [95% CI 0.31-1.48]), respectively, but more frequently stopped liraglutide due to gastrointestinal side effects (adjusted OR 2.32 [95% CI 1.45-3.74] and 2.37 [95% CI 0.97-5.81]), respectively.Minor hypoglycaemia and acute renal failure were uncommonly reported and were not more frequent among patients with renal impairment. Patients remaining on treatment in all three groups achieved significant HbA1c and weight reduction at six months (between -11 to -12mmol/mol [-1.0 to -1.1%] and -3.6 to -3.8kg). No effect of renal function was seen influencing the degree of HbA1c and weight reduction. Liraglutide treatment was associated with a small reduction in serum creatinine among patients with renal impairment.We concluded that liraglutide was safe, efficacious but more frequently discontinued among patients with mild renal impairment. More data are needed to establish its safety among patients with moderate or more significant renal impairment.

The influence of age and metformin treatment status on reported gastrointestinal side effects with liraglutide treatment in type 2 diabetes

“…However, when adjusted for other variables including age, renal function became non-significantly associated with GISE outcomes. A pharmacokinetic study testing the 0.75 mg dose of liraglutide showed no increase in drug exposure in patients with renal impairment [17]. The Prescribing Information for liraglutide have reported that liraglutide is metabolised endogenously much like large proteins rather than having a specific organ as a major route of elimination, and with no significant elimination through the faeces or urine [14].…”

What have we learnt from “real world” data, observational studies and meta‐analyses

“…ABCD also conducted an audit on the safety and efficacy of liraglutide 1.2 mg daily in 1791 patients with mild and moderate renal impairment and found that at 6 months there were significant reductions in HbA1c (−1.0 to −1.1%) and weight (−3.6 to −3.8 kg) which was not affected by degree of renal function . Minor hypoglycaemia was not more commonly reported in those with renal impairment and GI side effects were likely to occur at all stages of renal function although those with mild and moderate renal impairment were more likely to discontinue liraglutide (adjusted OR 2.32 [95% CI 1.45‐3.74] and 2.37 [95% CI 0.97‐5.81]), respectively.…”

Effectiveness and Persistence with Liraglutide Among Patients with Type 2 Diabetes in Routine Clinical Practice—EVIDENCE: A Prospective, 2-Year Follow-Up, Observational, Post-Marketing Study

“…The Association of British Clinical Diabetologists (ABCD) conducted a nationwide audit in the UK to assess the safety and effectiveness of liraglutide in real-life clinical practice. Data from this audit demonstrated that, after 6 months of treatment, liraglutide 1.2 mg was effective in terms of reducing HbA 1c (more so in individuals with a higher baseline HbA 1c ) and well tolerated [ 9 , 10 ]. Furthermore, data from the IMS Health integrated claims database in the USA demonstrate that, in clinical practice, liraglutide (once daily) has greater effectiveness [in terms of HbA 1c reduction and improved glycemic goal attainment (HbA 1c <7.0%)] compared with either exenatide (GLP-1RA, twice daily) or sitagliptin [dipeptidyl peptidase-4 (DPP-4) inhibitor, once daily] in patients with T2D [ 11 ].…”