Article
Source: Campus Sanofi

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.

Frias PF, Frias JP. New Basal Insulins: a Clinical Perspective of Their Use in the Treatment of Type 2 Diabetes and Novel Treatment Options Beyond Basal Insulin. Curr Diab Rep. 2017;17(10):91. doi: 10.1007/s11892-017-0926-8. PMID: 28822051