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

AIM: Treatment of type 2 diabetes with glucagon-like peptide-1 (GLP-1) receptor agonists may be limited by gastrointestinal side effects (GISE) in some patients. Risk factors for developing GISE are not known. We analysed patient characteristics that were associated with GISE among patients treated with the GLP-1 receptor agonist liraglutide. METHODS: Data was obtained from an audit database of liraglutide use based in clinical practice in the UK. Patients were grouped into those who did not report GISE, those who reported GISE but continued liraglutide and those who discontinued liraglutide due to GISE within 26 weeks of treatment. Baseline variables of age, diabetes duration, HbA1c, weight, BMI, blood pressure, lipids, gender, ethnicity, alanine transaminotransferase, estimated glomerular filtration rate (eGFR) and diabetes treatment types were tested for possible associations with GISE outcome. Significant variables in univariate analyses were entered into ordinal logistic regression analyses. RESULTS: A total of 4442 patients were suitable for analysis. A total of 3905 (87.9%) did not report GISE, 297 (6.7%) and 240 (5.4%) had GISE and continued and discontinued treatment, respectively. Age, weight, eGFR, metformin status and insulin status were associated with GISE outcome in univariate analyses (P all <0.05). In the final regression model, age (adjusted OR 1.15 [95%CI 1.05,1.26], P=0.002) and non-metformin use (adjusted OR 0.76 [95%CI 0.60,0.96], P=0.020) were associated with worse GISE outcome. CONCLUSION: Older age and non-metformin use were associated with more significant GISE leading to discontinuation of liraglutide treatment. The reasons for these findings are unclear and warrant further investigation.