Clinical efficacy and predictors of response to dulaglutide in type-2 diabetes

Pharmacol Res. 2020 Sep:159:104996. doi: 10.1016/j.phrs.2020.104996. Epub 2020 Jun 20.

Abstract

Aim of this retrospective multicenter observational study was to evaluate the efficacy and safety of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) dulaglutide in a type-2 diabetic real-world population and to determine the factors predicting the response in terms of glycated haemoglobin (HbA1c) and other relevant clinical outcomes. Data for efficacy outcomes, adverse events and drug discontinuation were collected from records of patients with type-2 diabetes treated with once-a-week 1.5 mg of dulaglutide for 12 months in routine clinical practice. Initial analysis included 782 patients and 626 had complete follow-up at 6- and 12-months. There was a significant reduction of HbA1c at 6 months (-1 ± 0.8 %, p < 0.0001), which remained stable at 12-months follow-up (-1 ± 0.9 %, p < 0.0001). The percentage of subjects with HbA1c≤7.0 % increased significantly from 7.2 % at baseline to 52.7 % at 6 months to 55.8 % at 12 months. Predictors of the achievement of HbA1c≤7.0 % were low baseline HbA1c and short duration of diabetes. The reduction of HbA1c was associated with reductions of BMI, waist circumference, fasting plasma glucose and blood pressures. Neither sex nor age had significant effects on any clinical or laboratory outcome. The effects of dulaglutide on HbA1c, BMI and SBP tended to be greater in patients who shifted from dipeptidyl peptidase-IV inhibitors (-0.8 ± 0.8 %) than other GLP-1 RA, even if an improvement of HbA1c reduction (-0.5 %) was also seen in those shifting from other GLP-1 RA. This study confirms that addition of dulaglutide 1.5 mg once a week in real word settings has beneficial effects on both clinical and laboratory outcomes in patients with uncontrolled type-2 diabetes. Dulaglutide has a greater effect on HbA1c in patients with higher baseline values and helps achieve a target HbA1c≤7.0 %, more consistently in patients with lower baseline HbA1c and shorter diabetes duration.

Keywords: Body weight; Diabetes treatment; Glucagon-Like peptide-1 receptor agonist; Glycated haemoglobin.

Publication types

  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers / blood
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucagon-Like Peptide-1 Receptor / agonists
  • Glucagon-Like Peptides / adverse effects
  • Glucagon-Like Peptides / analogs & derivatives*
  • Glucagon-Like Peptides / therapeutic use
  • Glycated Hemoglobin / metabolism*
  • Glycemic Control* / adverse effects
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Immunoglobulin Fc Fragments / adverse effects
  • Immunoglobulin Fc Fragments / therapeutic use*
  • Italy
  • Male
  • Middle Aged
  • Recombinant Fusion Proteins / adverse effects
  • Recombinant Fusion Proteins / therapeutic use*
  • Retrospective Studies
  • Time Factors
  • Treatment Outcome
  • Weight Loss / drug effects

Substances

  • Biomarkers
  • Blood Glucose
  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Immunoglobulin Fc Fragments
  • Recombinant Fusion Proteins
  • hemoglobin A1c protein, human
  • Glucagon-Like Peptides
  • dulaglutide