Translating iGlarLixi Evidence for the Management of Frequent Clinical Scenarios in Type 2 Diabetes

Abstract

Treatment of type 2 diabetes (T2D) requires progressive therapy intensification to reach and maintain individualized glycemic targets. iGlarLixi, a fixed-ratio combination of insulin glargine 100 U/mL (iGlar) and lixisenatide (Lixi), has been shown to provide robust HbA 1c reductions allowing more people to reach HbA 1c targets compared with separate administration of iGlar or Lixi. The purpose of this review is to help clinicians understand treatment intensification using iGlarLixi by presenting typical clinical scenarios supported by research evidence. These cases will focus on individuals with T2D inadequately controlled by oral antihyperglycemic drugs, basal insulin, or glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and take into consideration T2D duration, body mass index, incidence of adverse events, and regimen simplicity. Clinical evidence on the efficacy, effectiveness, and safety of iGlarLixi from randomized controlled trials and real-world studies will be discussed in the context of these cases.

Titratable fixed‐ratio combination of basal insulin plus a glucagon‐like peptide‐1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes

“…33 Briefly, the results of these studies showed that iGlarLixi provided greater HbA1c reductions and improved glycaemic control compared with other regimens, with a similar risk of hypoglycaemia and more favourable weight change profiles compared with iGlar and fewer gastrointestinal adverse events compared with Lixi alone. [31][32][33][34] An NMA of 17 studies comparing gastrointestinal events with iGlarLixi compared with GLP-1 RAs during the first 12 weeks of therapy showed that fewer participants in the iGlarLixi treatment group reported nausea compared with short-acting GLP-1 RAs, and vomiting was also less common with iGlarLixi compared with use of a single-agent GLP-1 RA. 35 The pivotal studies of the DUAL RCT programme compared the safety and efficacy of IDegLira versus either IDeg alone or Lira alone in people with T2D uncontrolled on OAD therapy (DUAL I), 36 versus continued use of IDeg in people with T2D uncontrolled on IDeg with OADs (DUAL II), 37 or versus continued use of GLP-1 RAs in people with T2D uncontrolled on GLP-1 RAs and OADs (DUAL III).…”

“…The LixiLan RCT programme compared the safety and efficacy of iGlarLixi with those of: iGlar alone and Lixi alone in people with T2D uncontrolled on OADs (LixiLan‐O) 31 ; basal insulin in people with T2D uncontrolled on basal insulin with OADs (LixiLan‐L) 32 ; or GLP‐1 RA therapy in people with T2D uncontrolled on GLP‐1 RAs (LixiLan‐G) 33 . Briefly, the results of these studies showed that iGlarLixi provided greater HbA1c reductions and improved glycaemic control compared with other regimens, with a similar risk of hypoglycaemia and more favourable weight change profiles compared with iGlar and fewer gastrointestinal adverse events compared with Lixi alone 31–34 . An NMA of 17 studies comparing gastrointestinal events with iGlarLixi compared with GLP‐1 RAs during the first 12 weeks of therapy showed that fewer participants in the iGlarLixi treatment group reported nausea compared with short‐acting GLP‐1 RAs, and vomiting was also less common with iGlarLixi compared with use of a single‐agent GLP‐1 RA 35 …”

Effectiveness of IGlarLixi, a Fixed-Ratio Combination of Insulin Glargine 100 U/mL and Lixisenatide, in People with Type 2 Diabetes

“…These covered questions such as sequential versus simultaneous initiation of insulin glargine and lixisenatide, de-intensification from the basal-bolus insulin regimen to iGlarLixi, discontinuation of OADs when initiating the iGlarLixi FRC and the advantages of iGlarLixi injection pens. Skolnik et al [20] have demonstrated the applicability of iGlarLixi in real-world cases.…”

Expert Opinion on Diabetes Management Challenges and Role of Basal Insulin/GLP-1 RA Fixed-Ratio Combination in People with Type 2 Diabetes from Indonesia

“…If a patient has not been diagnosed with CV disease: • Glycemic control and achieving individual HbA 1c target levels are the most important aspects in patients with no CV disease; and either of FRCs, ie, iDegLira or iGlarLixi, can be used, which is consistent with ADA-EASD recommendations. [46][47][48] What Should Be Done When FRC is No Longer Sufficient to Provide Good Glycemic Control?…”

“…This FRC has several advantages, such as the delivery of multidrug components through a single-daily injection, improvement of FPG, reduction of PPG without increasing hypoglycemia risk, and mitigation of risk of weight gain with improved GI tolerability. 26,46 People with T2DM who are unable to achieve their glycemic targets may benefit from the FRC complementary actions of basal insulin, which predominantly targets FPG, and GLP1RA, which predominantly targets PPG levels. 47 Overall, the development of the FRC follows a patient-centric treatment approach since FRC offers many advantages over administering its component treatments individually.…”