![]() ![]() Treatment with IDegLira reduced A1C across the studies (ranging from −1.3 to −1.9%), and these reductions were consistently greater than those seen with the comparators (−0.9 to −1.4% with insulin degludec in DUAL I and II, −1.3% with liraglutide in DUAL I, −1.13% with insulin glargine U100 in DUAL V, and −0.5% with placebo in DUAL IV). The DUAL series of phase 3 clinical trials looked at the use of IDegLira for intensifying treatment in a range of patient populations: insulin-naive (DUAL I and IV), insulin experienced (DUAL II, V, and VII), and those already on a GLP-1 receptor agonist (DUAL III). 0.5%, respectively, in LixiLan-L), and resulted in very low treatment discontinuation rates (0.4% due to nausea or vomiting and 0.2% due to diarrhea in LixiLan-O 1.1% due to nausea in LixiLan-L) ( 33, 34). 3.6%, respectively, in LixiLan-O 10.4 vs. 24.0%, respectively, in LixiLan-O) ( 33), but higher than with insulin alone (nausea: 9.6 vs. The incidence of gastrointestinal adverse events (AEs) was lower with iGlarLixi than with lixisenatide alone (nausea: 9.6 vs. iGlarLixi also mitigated the weight gain seen with insulin glargine U100 in both trials (LixiLan-O: −0.3 and +1.1 kg for iGlarLixi and insulin glargine U100, respectively LixiLan-L: −0.7 and +0.7 kg for iGlarLixi and insulin glargine U100, respectively) ( Table 1). 23.6 and 42.5% in LixiLan-O and LixiLan-L, respectively), although it was higher than with lixisenatide alone (6.4% in LixiLan-O). The incidence of symptomatic hypoglycemia (≤70 mg/dL) with iGlarLixi was similar to that of basal insulin (25.6 and 40.0% vs. insulin glargine U100 in both trials and vs. 59.4% for insulin glargine U100 and 33.0% for lixisenatide LixiLan-L: 54.9% for iGlarLixi vs. A larger proportion of patients treated with iGlarLixi achieved a target A1C of <7.0% across studies (LixiLan-O: 73.7% for iGlarLixi vs. In LixiLan-O, A1C reductions were −1.6, −1.3, and −0.9% in patients treated with iGlarLixi, insulin glargine U100, and lixisenatide, respectively in LixiLan-L, reductions were −1.1 and −0.6% for patients treated with iGlarLixi and insulin glargine U100, respectively. IGlarLixi consistently led to significantly greater A1C reductions than the comparators. IGlar + insulin aspart: 8.17 episodes/PYE † Previous GLP-1 RA + metformin ± another OAD ![]() ![]() Previous insulin + metformin ± another OAD Unlike longer-acting GLP-1 receptor agonists, its effects on gastric emptying or PPG levels do not disappear because they do not seem to be subjected to tachyphylaxis ( 28). Although lixisenatide has a shorter half-life, it retains the ability to reduce PPG with once-daily dosing through reduction of PPG exposure after meals. It has a half-life of 2–3 hours and acts mainly by delaying gastric emptying, exerting a pronounced PPG-lowering effect with a lesser effect on FPG at doses as low as 2.5 µg ( 25– 27). Lixisenatide is a once-daily, shorter-acting GLP-1 receptor agonist recently approved in the United States for the treatment of patients with type 2 diabetes as an adjunct to diet and exercise to improve glycemic control. Its pharmacologic effects are well characterized once-daily insulin glargine U100 results in glucose-lowering activity for up to 24 hours, with blood glucose values of 130 mg/dL maintained until 15 hours and then slightly increasing to ∼140 mg/dL between 16 and 24 hours ( 24). Insulin glargine U100 is a mainstay of long-acting basal insulin therapy and was first approved for clinical use in 2000. IGlarLixi is a combination of insulin glargine U100 with lixisenatide. ![]()
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