Basal Insulin Treatment in Type 2 Diabetes

Abstract

Insulin glargine is the first 24-h recombinant DNA insulin analog introduced to the market. Substitution of glycine for asparagine and addition of two arginine residues raise the isoelectric point of insulin glargine and result in microprecipitates, delaying absorption from subcutaneous tissue. This delayed absorption result in fairly flat 24-h insulin concentration profiles with no discernible peak. Large, multicenter, randomized, controlled trials in patients with type 2 diabetes show that although NPH insulin and insulin glargine are equally effective in lowering glycosylated hemoglobin (A1c) and fasting blood glucose, there is a clear advantage of insulin glargine over NPH insulin in reducing nocturnal and overall hypoglycemia. Lower risk of hypoglycemia with glargine was also consistently demonstrated by trials comparing insulin glargine and premixed analog insulins. These studies also showed greater reduction in A1c with twice-daily premixed insulins compared with glargine, when insulin glargine was administered without mealtime insulin coverage. Insulin glargine was also compared with another insulin analog, insulin detemir. Trials showed that both insulin analogs are equally effective in lowering A1c and have comparable risk of hypoglycemia. Trials comparing insulin glargine with glucagon-like peptide-1 agonists showed comparable significant reductions in A1c with both regimens. Insulin glargine is well tolerated, has low immunogenicity, reduced risks for acute myocardial infarction, and a lower risk of hypoglycemia compared with NPH insulin in individuals with type 2 diabetes.

Effect of prandial treatment timing adjustment, based on continuous glucose monitoring, in patients with type 2 diabetes uncontrolled with once‐daily basal insulin: A randomized, phase IV study

“…The primary approach in reducing glycaemic load is addition and up‐titrating of long‐acting basal insulin injection, which affects both pre‐ and postprandial glucose. However, PPG control is necessary for patients who are close to, but not at, target (HbA1c < 7%), for those using high doses of basal insulin without success (>0.7 U/kg) or those who are at increased risk of nocturnal hypoglycaemia which prevents further titration of basal insulin doses . This can be addressed by administration of a rapid‐acting insulin analogue at mealtime, producing a rapid and short insulin spike to control the PPG elevation.…”

Stepwise intensification of insulin therapy in Type 2 diabetes management—exploring the concept of the basal‐plus approach in clinical practice

“…These include insulin lispro 75/25 (75% insulin lispro protamine suspension plus 25% insulin lispro), biphasic insulin aspart 70/30 (70% insulin aspart protamine suspension plus 30% insulin aspart) and insulin lispro 50/50 (50% insulin lispro protamine suspension plus 50% insulin lispro). Randomized controlled trials have demonstrated that twice‐daily insulin lispro 75/25 or insulin aspart 70/30 and three‐times daily insulin lispro 50/50 are significantly superior to basal insulin alone in providing overall and postprandial glycaemic control . Premixed insulins are, however, associated with an increased risk of daytime hypoglycaemia compared with basal insulin alone.…”

When basal insulin is not enough: A dose–response relationship between insulin glargine 100 units/mL and glycaemic control

“…2 The introduction of basal insulin analogues more than a decade ago has made it easier for primary care physicians to engage in the treatment of insulin-requiring patients and to intensify insulin therapy, with lower rates of hypoglycaemia achieved compared with non-modified human insulins. 3 This is critically important because~90% of type 2 diabetes care is carried out in the primary care setting. 4,5 Treat-to-target titration trials have helped define the initiation and titration of basal insulin analogues contingent on achieving fasting plasma glucose (FPG) targets.…”