Basal Insulin and Beyond: Advanced Therapies for Type 2 Diabetes

Novel basal insulins and fixed-ratio combinations of basal insulin and GLP-1RA are safer and more convenient options for uncontrolled type 2 diabetes.

Main Takeaway

• This review informs about new and advanced therapeutic options available for patients with type 2 diabetes (T2D) uncontrolled with oral antidiabetic drugs (OADs).

• Basal insulin (BI), with its advanced new formulations, is an important therapeutic option in patients with advancing T2D.

• If BI is insufficient in achieving the desired glycaemic goals, treatment intensification with prandial insulin, pre-mixed insulin or glucagon-like peptide-1 receptor agonist (GLP-1RA) should be considered.

• Recently, ‘fixed-ratio combinations’ (FRCs) of BI and GLP-1RA have been approved for use with safe and effective antihyperglycaemic profiles whilst reducing injection burden, thereby promoting adherence.

Key Highlights

• As T2D is a progressive disorder, most patients eventually require insulin therapy to obtain optimal glycaemic control.

• The American Diabetes Association (ADA), European Association for the Study of Diabetes and American Association of Clinical Endocrinologists recommend the early use of BI in the course of T2D treatment.

• Generally, BI therapy is initiated on non-achievement of glycaemic targets after receiving 2-3 OADs.

• Advances in BI formulations have led to flatter and longer action profiles, resulting in a significant reduction in hypoglycaemia.

• Recent BI analogues are easy to initiate as a once-daily injection.

• However, insulin dosing and subsequent titration are prescribed on the basis of insulin formulations and clinician and patient preferences.

• Recommended insulin initiation dosages vary with formulations, but are generally conservative to reduce the risk for hypoglycaemia.

• Post-initiation, BI should be appropriately titrated to achieve optimal fasting plasma glucose targets.

• If the daily BI dose is approximately >0.5 U/kg and glycated haemoglobin (HbA1c) targets are unmet, initiation of combination injectable therapies should be considered, primarily to address postprandial hyperglycaemia.

• Three options of therapy intensification recommended by the ADA include the addition of rapid-acting insulin, switching to premixed insulin and addition of GLP-1RA.

• Insulin intensification increases the risk for hypoglycaemia and weight gain with the increased need for self-monitoring of blood glucose levels.

• Addition of GLP-1RA to existing BI therapy results in similar HbA1c reductions compared with basal-bolus insulin therapy, with a decreased risk for hypoglycaemia and weight gain.

  • However, gastrointestinal side effects are common with GLP-1RA and its use should be contraindicated or cautionary in at-risk patient populations.

• Recently, FRCs of BI and GLP-1RA have been approved for T2D treatment.

• Studies indicate that in patients suboptimally controlled on OADs or BI, FRCs (vs individual components) have the following beneficial effects:

  • significant improvement in glycaemic control with 55-75% of patients achieving HbA1c <7.0%;

  • mitigation of weight gain and no higher risk for hypoglycaemia vs BI alone; and

  • reduced gastrointestinal side effects vs GLP-1RA alone.

• In patients not achieving glycaemic targets with less than 50-60 U BI, FRCs are a safe and effective option with convenient once-daily subcutaneous injectable dosing.

MAT-BH-2300617/v1/October 2023