Meta-analysis of 15 studies demonstrated that the combination of GLP-1 RA and basal insulin, in comparison with other anti-diabetic treatments, can enable achievement of robust glycemic control, without increased risk of hypoglycemia and weight gain [7].
Our results are in agreement with GetGoal-L and GG-Duo1 randomized clinical trials (RCT) [8, 9]. In both studies lixisenatide led to a significant decrease in HbA1c up to − 0.7%, lowered body weight and was associated with lower insulin dose. In conclusion, lixisenatide could be considered as an alternative to prandial insulin in T2DM patients sub-optimally controlled on basal insulin which is now supported with real life data.
The GetGoal Duo 2 study is the first trial to directly compare lixisenatide with prandial insulin in combination with basal insulin [6]. The results of the study showed that lixisenatide brings the combined benefit of HbA1c management in line with bolus insulins but with weight reduction as opposed to the usual weight gain and with lower risk of hypoglycemia and lower total insulin dose. Similarly, results of the LIRA-ADD2BASAL study where liraglutide was added to preexisting basal insulin, showed significantly more patients within glycemic targets with addition of this long acting GLP1-RA, and also higher proportion of patients reaching composite end-points, with additional weight reduction and low hypoglycemia risk [10]. Recently published data on DUAL VII RCT showed superior results of fixed combination of IDegLira compared to basal-bolus insulin regimen in risk of hypoglycemia and weight at comparable glycemic control [11], bringing the combination of GLP1-RA and basal insulin in the spot light of treatment intensification of T2DM.
In our real-life study, we have provided evidence of additional benefits besides weight reduction and decrease in total insulin doses such as significant reduction in HbA1c in majority of patients. Furthermore, this combination is interesting also due to the pathophysiological background of DMT2, while beta-cell function is severely impaired in progressed DMT2, and short acting glucagon-like peptide-1 receptor agonists (GLP1-RA) has a pronounced effect on GIT motility [12].
It is evident that insulin initiation is delayed with multiple oral antidiabetic (OAD) combinations, but one of the biggest challenge in clinical practice especially in Croatia are sub-optimally regulated premix and basal bolus patients who often come with the problems of hypoglycemia and weight gain. In addition, health reimbursement restrictions for GLP1-RA in Croatia (BMI > 35) reduces the pool of potential patients for GLP1 therapy [13]. However, according to our data those patients with BMI over 35 kg/m2 treated with different insulin regimes regardless of baseline HbA1c level and duration of diabetes could benefit from this specific combination with regard to not only weight and hypoglycemia reduction, but also HbA1c improvement. The biggest success of this change in treatment was noted in patients treated with premix insulins.
The main limitation of this study is non-interventional observational design and availability of only routine data. Also, some clinical events such as hypoglycemic episodes were omitted or underreported which disabled analysis of those data. The strength lays in the uniqueness of data presented since no real life data exist regarding lixisenatide in combination with basal insulin, especially not in previously insulin treated patients.