Fixed-Ratio Combinations of Basal Insulin and GLP-1RA in the Management of Type 2 Diabetes Mellitus: Highlights from the Literature

Introduction New pieces of evidence suggest that combining basal insulin with glucagone-like peptide 1 receptor agonists (GLP-1RA) in patients with type 2 diabetes could promptly ameliorate glucose control and prevent both hypoglycemic events and unnecessary weight gain compared to more intensive insulin regimens. Aim To review the efficacy/effectiveness and safety of fixed-ratio combinations of basal insulin and GLP-1RA (FRCs). Methods Authors searched PubMed/MEDLINE, ClinicalTrials.gov, Cochrane Library, and Google Scholar for freely available original articles, randomized clinical trials (RCTs), clinical reviews, and meta-analysis written in English until January 2020. Results FRCs provide significative reductions in HbA1c levels in both insulin-naïve (-1.4% to -2%) and insulin-experienced (-1.5% to -2%) type 2 diabetic patients with moderate glucose impairment. More patients achieved the recommended glycemic targets on FRCs compared to those on monotherapy with basal insulin or GLP-1RAs. The intensification with FRCs results in better glycemic control compared to basal insulin at fasting as well as during the postprandial state. The frequency of hypoglycemia is similar or lower in patients treated with FRCs than in those on basal insulin alone at a similar dose. Weight trend can be variable, ranging from -2.7 to +2 Kg for iDegLira and -0.7 to -1.3 Kg for iGlarLixi. However, a lower weight gain is obtained with iDegLira compared to iDeg (-2.2 to - 2.5 Kg), iGlar (-1.7 to -3.2 Kg), and basal-bolus (-3.6 Kg) as well as with iGlarLixi compared to iGlar (-1.4 Kg). Discussion and Conclusion FRCs should be considered to safely improve the metabolic control in type 2 diabetic patients with moderate glycemic impairment while on oral medications, basal oral regimen or GLP-1RAs. However, a few but significative pieces of evidence suggest that FRCs could be a safe and effective treatment instead of a low dose basal-bolus intensification for patients with mild or moderate glucose impairment in order to reduce the risk of hypoglycemia and unnecessary weight gain, and for simplifying treatment regimen as well.