Comparison of insulin lispro protamine suspension versus insulin glargine once daily added to oral antihyperglycaemic medications and exenatide in type 2 diabetes: a prospective randomized open-label trial

Diabetes Obes Metab. 2014 Jun;16(6):510-8. doi: 10.1111/dom.12242. Epub 2013 Dec 29.

Abstract

Aims: To compare efficacy and safety of two, once-daily basal insulin formulations [insulin lispro protamine suspension (ILPS) vs. insulin glargine (glargine)] added to oral antihyperglycaemic medications (OAMs) and exenatide BID in suboptimally controlled type 2 diabetes (T2D) patients.

Methods: This 24-week, open-label, multicentre trial randomized patients to bedtime ILPS (n = 171) or glargine (n = 168). Non-inferiority of ILPS versus glargine was assessed by comparing the upper limit of 95% confidence intervals (CIs) for change in haemoglobin A1c (HbA1c) from baseline to week 24 (adjusted for baseline HbA1c) with non-inferiority margin 0.4%.

Results: Non-inferiority of ILPS versus glargine was demonstrated: least-squares mean between-treatment difference (ILPS minus glargine) (95% CI) was 0.22% (0.06, 0.38). Mean HbA1c reduction was less for ILPS- versus glargine-treated patients (-1.16 ± 0.84 vs. -1.40 ± 0.97%, p = 0.008). Endpoint HbA1c < 7.0% was achieved by 53.7% (ILPS) and 61.7% (glargine) (p = NS). Overall hypoglycaemia rates (p = NS) and severe hypoglycaemia incidence (p = NS) were similar. Nocturnal hypoglycaemia rate was higher in patients treated with ILPS versus glargine (p = 0.004). Weight gain was similar between groups (ILPS: 0.27 ± 3.38 kg; glargine: 0.66 ± 3.93 kg, p = NS). Endpoint total insulin doses were lower in patients treated with ILPS versus glargine (0.30 ± 0.17 vs. 0.37 ± 0.17 IU/kg/day, p < 0.001).

Conclusions: ILPS was non-inferior to glargine for HbA1c change over 24 weeks, but was associated with less HbA1c reduction and more nocturnal hypoglycaemia. Treat-to-target basal insulin therapy improves glycaemic control and is associated with minimal weight gain when added to OAMs and exenatide BID for suboptimally controlled T2D.

Keywords: HbA1c; exenatide; glucagon-like peptide-1 receptor agonist therapy; glycaemic control; hypoglycaemia; insulin glargine; insulin lispro protamine suspension; type 2 diabetes.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adolescent
  • Adult
  • Aged
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hyperglycemia / drug therapy*
  • Hyperglycemia / metabolism
  • Hypoglycemia / chemically induced
  • Hypoglycemic Agents / administration & dosage*
  • Hypoglycemic Agents / adverse effects
  • Insulin Glargine
  • Insulin Lispro / administration & dosage*
  • Insulin Lispro / adverse effects
  • Insulin, Long-Acting / administration & dosage*
  • Insulin, Long-Acting / adverse effects
  • Male
  • Middle Aged
  • Protamines / administration & dosage
  • Protamines / adverse effects
  • Treatment Outcome
  • Weight Gain
  • Young Adult

Substances

  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Lispro
  • Insulin, Long-Acting
  • Protamines
  • hemoglobin A1c protein, human
  • Insulin Glargine