Basal insulin combined incretin mimetic therapy with glucagon-like protein 1 receptor agonists as an upcoming option in the treatment of type 2 diabetes: a practical guide to decision making

Abstract

Abstract:The combination of basal insulin and glucagon-like protein 1 receptor agonists (GLP-1 RAs) is a new intriguing therapeutic option for patients with type 2 diabetes. In our daily practice we abbreviate this therapeutic concept with the term BIT (basal insulin combined incretin mimetic therapy) in a certain analogy to BOT (basal insulin supported oral therapy). In most cases BIT is indeed an extension of BOT, if fasting, prandial or postprandial blood glucose values have not reached the target range. In our paper we discuss special features of combinations of short-or prandial-acting and long-or continuous-acting GLP-1 RAs like exenatide, lixisenatide and liraglutide with basal insulin in relation to different glycemic targets. Overall it seems appropriate to use a short-acting GLP-1 RA if, after the near normalization of fasting blood glucose with BOT, the prandial or postprandial values are elevated. A long-acting GLP-1 RA might well be given, if fasting blood glucose values are the problem. Based on pathophysiological findings, recent clinical studies and our experience with BIT and BOT as well as BOTplus we developed chart-supported algorithms for decision making, including features and conditions of patients. The development of these practical tools was guided by the need for a more individualized antidiabetic therapy and the availability of the new BIT principle.

The Role of Glucagon-Like Peptide-1 Receptor Agonists in Type 2 Diabetes: Understanding How Data Can Inform Clinical Practice in Korea

“…For example, adding exenatide twice-daily to basal insulin (alone or in combination with metformin and/or pioglitazone), lead to significant reductions in morning and evening 2-hour postprandial excursions (both P <0.001 vs. placebo) [ 35 ] whilst lixisenatide 20 µg once a day has been shown to significantly reduce postprandial glucose when compared with placebo after breakfast ( P <0.0001), lunch ( P <0.001), and dinner ( P <0.05) [ 35 36 ]. It is because of this effect on postprandial glucose that short-acting GLP-1RAs may be considered as prandial-acting GLP-1RAs [ 9 34 37 ].…”

“…These include a reduction HbA1c levels, weight maintenance or loss, and a relatively low risk of hypoglycemia. These benefits are offset against the propensity for GI adverse effects early in the course of treatment and a lack of long-term outcomes data [ 37 ].…”

“…Other clinical factors that may aid in treatment choice include uncontrolled HbA1c due to high postprandial (rather than fasting) blood glucose levels, need to control weight particularly amongst patients who already have a basal insulin as part of their regimen, patients at increased risk of hypoglycemia and patients with or at high risk of CV comorbidities, such as hypertension and fatty liver. The different pharmacodynamic features of GLP-1RAs may help guide the decision to administer a GLP-1RA with basal insulin; using short-acting lixisenatide or exenatide twice-daily in patients with prandial or postprandial hyperglycemia after near normalisation of fasting blood glucose and long-acting exenatide LAR, liraglutide, albiglutide or dulaglutide if the main concern is elevated fasting blood glucose levels [ 37 ].…”

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“…Combining incretin-based therapies with basal insulin provides complementary actions to improve glycemic control in diabetes management, for example [46]. Theoretically, incretin-based therapies are an alternative to bolus insulin for certain groups of patients, such as the elderly, where meeting HgbA1C targets must be balanced against the risk of hypoglycaemia [46]. The improvements in glycemic control may reduce the incidence of diabetes-related complications, and an incretin plus basal insulin regimen may reduce risk of hypoglycaemia [47,48].…”

“…Newer classes of anti-diabetes medication, such as incretin-based therapies and SGLT2 inhibitors, have the potential to be used not only for monotherapy but also in combination with any of the existing classes of glucose-lowering agents, including insulin [45]. Combining incretin-based therapies with basal insulin provides complementary actions to improve glycemic control in diabetes management, for example [46]. Theoretically, incretin-based therapies are an alternative to bolus insulin for certain groups of patients, such as the elderly, where meeting HgbA1C targets must be balanced against the risk of hypoglycaemia [46].…”