Combining GLP-1 Receptor Agonists and Basal Insulin in Older Adults with Type 2 Diabetes: Focus on Lixisenatide and Insulin Glargine

Abstract

Estimates suggest that there are currently 122.8 million adults 65-99 years of age living with diabetes, of whom 90-95% are diagnosed with type 2 diabetes (T2D). Over the past two decades, a greater understanding of the complex and multifactorial pathogenesis of T2D has resulted in the development and introduction of new-generation classes of glucose-lowering therapies, which are now extensively endorsed by prevailing guidelines and are increasingly being used worldwide. These newer agents may further assist in the effective pharmacological management of T2D through the provision of patient-centered care that acknowledges multimorbidity and is respectful of and responsive to individual patient preferences and barriers. Given these considerations, the therapeutic approach in older patients with T2D is complex, particularly in those who have functional dependence, frailty, dementia, or who are at end-of-life. It is currently too early to draw conclusions on the long-term use of newer glucose-lowering agents in this population, as their efficacy and safety in older adults remains largely unknown. In this review, we will discuss considerations for the use of glucose-lowering treatments in older adults, with particular focus on the use of basal insulin and glucagon-like peptide-1 receptor agonists, and the rationale for the use of combination therapy comprising these agents. Finally, we will review clinical data from studies of the fixed-ratio combination of insulin glargine and lixisenatide in older patients with T2D.

Direct comparison two fixed-ratio combination glucagon-like peptide receptor agonist and basal insulin on glycemic and non glycemic parameters in type 2 diabetes

“…Differences in uptake across the blood–brain barrier (or in brain access through subfornical organs) have been postulated as an explanation [ 20 – 23 ]. Clinical trial data from patients receiving fixed-ratio combination showed a weight change of − 0,3 to − 0,7 kg for iGlarLixi and − 2 to − 2,7 kg for iDegLira [ 12 , 13 , 16 , 17 , 24 ].…”

An Overview of Incretin-Based Therapies: Pharmacology and Future Perspectives

“…Although its apparently short half-life, it reduces postprandial glucose levels with once daily dosing through the day which is primarily mediated via delayed gastric emptying 31 . According to previous clinical studies, lixisenatide showed significant beneficial effects on postprandial blood glucose levels and HbA1c reduction in various settings, involving when used as monotherapy and add-on to oral antidiabetics and basal insulin 32 . The starting dose of lixisenatide is 10 µg daily for 2 weeks, which on day 15 is titrated to 20 µg daily.…”

Charting the next century of insulin replacement with cell and gene therapies

“…37 Therefore, GLP-1 receptor agonists (RAs) have been developed and are shown to be effective in glucose lowering when prescribed to individuals with T2D. 38 The first two combinations of insulin with GLP- Review degludec or glargine with a GLP-1 RA analog (liraglutide or lixisenatide, respectively) in a fixed ratio [19][20][21]39 (Table 1).…”