Nutritional Insulin or Glp-1 Receptor Agonist: Crossroads in the Treatment of Type 2 Diabetes Mellitus

Abstract

Type 2 diabetes mellitus (T2DM) is a progressive disease due to worsening of pancreatic beta cell function over time ( 1. Fonseca V.A. Defining and characterizing the progression of type 2 diabetes. Diabetes Care. 2009; 32: S151-S156 Crossref PubMed Google Scholar ). Patients with classical T2DM initially respond to noninsulin antidiabetic agents, but insulin therapy becomes essential at some point. Most patients treated with sulfonylurea drugs and metformin need insulin after about 9 years of therapy ( 2. Turner R.C. Cull C.A. Frighi V. Holman R.R. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: Progressive requirement for multiple therapies (UKPDS 49). UK Prospective Diabetes Study (UKPDS) Group. JAMA. 1999; 281: 2005-2012 Crossref PubMed Scopus (2167) Google Scholar ). Once required, insulin is often prescribed as a single daily injection of basal insulin. However, over time, more frequent injections are needed to control postprandial hyperglycemia and achieve a target level of glycated hemoglobin (HbA1c). While insulin is the most effective treatment for hyperglycemia, insulin use is associated with weight gain and increased risk of hypoglycemia ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar ). Moreover, multiple daily insulin injections are prone to errors and may be burdensome for many older patients with T2DM. Therefore, alternatives to daily insulin injections are welcomed by patients as well as their physicians. Adding a glucagon-like peptide-1 receptor agonist (GLP-1RA) to a treatment regimen that includes basal insulin and oral antidiabetic agents is an attractive option. Compared to the basal-bolus insulin regimen, it requires a smaller number of injections and is associated with lower risks of weight gain and hypoglycemia ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar ). A GLP-1RA may be added to the basal insulin therapy or vice versa. Randomized clinical trials have shown equivalent glycemic control with basal insulin plus a GLP-1RA and basal insulin plus nutritional insulin ( 3. Diamant M. Nauck M.A. Shaginian R. et al. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014; 37: 2763-2773 Crossref PubMed Scopus (198) Google Scholar , 4. Mathieu C. Rodbard H.W. Cariou B. et al. A comparison of adding liraglutide versus a single daily dose of insulin aspart to insulin degludec in subjects with type 2 diabetes (BEGIN: VICTOZA ADD-ON). Diabetes Obes Metab. 2014; 16: 636-644 Crossref PubMed Scopus (144) Google Scholar ). However, there are concerns about using GLP-1RA with insulin due to increased treatment cost.