Dose response of continuous subcutaneous infusion of recombinant glucagon-like peptide-1 in combination with metformin and sulphonylurea over 12 weeks in patients with type 2 diabetes mellitus

Diabetes Obes Metab. 2014 May;16(5):451-6. doi: 10.1111/dom.12240. Epub 2013 Dec 10.

Abstract

Aims: Any differences observed between natural glucagon-like peptide-1 (GLP-1) and studies obtained with analogues might call for renewed considerations concerning the use and design of such analogues. Thus, we aimed to evaluate the dose-response relationship of recombinant glucagon-like peptide-1 (7-36) amide (rGLP-1) administered by continuous subcutaneous infusion (CSCI) in subjects with type 2 diabetes.

Methods: We compared the efficacy and safety of three doses of recombinant GLP-1, ranging from 1.25 to 5.0 pmol/kg/min (pkm) and placebo, given by continuous subcutaneous infusion over 3 months in combination with metformin and sulphonylurea (SU), to lower haemoglobin A1c (HbA1c), fasting plasma glucose and weight in 95 type 2 diabetes patients with inadequate glycaemic control.

Results: The mean decreases in HbA1c at endpoint (week 12) were significantly greater for all three rGLP-1 dose groups when each was compared with the placebo group, with the greatest decrease occurring in the 5.0 pkm dose group (-1.3%, s.d. ± 0.18, p < 0.001). The mean decreases in fasting plasma glucose from baseline to endpoint were significantly greater for all three rGLP-1 dose groups than for the placebo group, with the greatest decrease occurring in the 5.0 pkm dose group (-26.0 mg/dl, s.d. ± 8.5, p = 0.02). Body weight was significantly reduced by 1.8 kg (s.d. ± 1.3) in the 1.25 pkm dose group only (p = 0.04).

Conclusions: Administration of rGLP-1 by CSCI over a 12-week period in combination with metformin and an SU had a dose dependent effect in lowering HbA1c and fasting plasma glucose. However, administration of rGLP-1 by CSCI may be less effective with respect to lowering of body weight compared with the daily and once weekly analogues.

Keywords: GLP-1; GLP-1 analogue; antidiabetic drug; antiobesity drug; clinical trial; dose-response relationship.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Blood Glucose / drug effects
  • Blood Glucose / metabolism
  • Body Weight / drug effects
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Glucagon-Like Peptide 1 / analogs & derivatives*
  • Glycated Hemoglobin A / drug effects
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / administration & dosage*
  • Infusions, Subcutaneous*
  • Male
  • Metformin / administration & dosage*
  • Middle Aged
  • Sulfonylurea Compounds / administration & dosage*
  • Time Factors

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Sulfonylurea Compounds
  • hemoglobin A1c protein, human
  • Glucagon-Like Peptide 1
  • Metformin