Rationale and methodology for a European pooled analysis of postmarketing interventional and observational studies of insulin glargine 300 U/mL in diabetes: protocol of REALI project

BMJ Open. 2020 Apr 28;10(4):e033659. doi: 10.1136/bmjopen-2019-033659.

Abstract

Introduction: Type 2 diabetes mellitus (T2DM) is a common and heterogeneous disease. Using advanced analytic approaches to explore real-world data may identify different disease characteristics, responses to treatment and progression patterns. Insulin glargine 300 units/mL (Gla-300) is a second-generation basal insulin analogue with preserved glucose-lowering efficacy but reduced risk of hypoglycaemia. The purpose of the REALI pooled analysis described in this paper is to advance the understanding of the effectiveness and real-world safety of Gla-300 based on a large European patient database of postmarketing interventional and observational studies.

Methods and analysis: In the current round of pooling, REALI will include data from up to 10 000 subjects with diabetes mellitus (mostly T2DM) from 20 European countries. Outcomes of interest include change from baseline to week 24 in haemoglobin A1c, fasting plasma glucose, self-measured plasma glucose, body weight, insulin dose, incidence and rate of any-time-of-the-day and nocturnal hypoglycaemia. The data pool is being investigated using two complementary methodologies: a conventional descriptive, univariate and multivariable prognostic analysis; and a data-mining approach using subgroup discovery to identify phenotypic clusters of patients who are highly associated with the outcome of interest. By mid-2019, deidentified data of 7584 patients were included in the REALI database, with a further expected increase in patient number in 2020 as a result of pooling additional studies.

Ethics and dissemination: The proposed study does not involve collection of primary data. Moreover, all individual study protocols were approved by independent local ethics committees, and all study participants provided written informed consent. Furthermore, patient data is deidentified before inclusion in the REALI database. Hence, there is no requirement for ethical approval. Results will be disseminated via peer-reviewed publications and presentations at international congresses as data are analysed.

Keywords: Europe; clinical practice; insulin glargine 300 units/mL; pooled analysis; type 2diabetes mellitus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Blood Glucose / analysis
  • Data Analysis
  • Databases, Factual / statistics & numerical data
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Disease Progression
  • Europe
  • Fasting / blood
  • Glycated Hemoglobin / analysis
  • Humans
  • Hypoglycemic Agents / administration & dosage
  • Hypoglycemic Agents / therapeutic use*
  • Insulin Glargine / administration & dosage
  • Insulin Glargine / therapeutic use*
  • Middle Aged
  • Multivariate Analysis
  • Observational Studies as Topic
  • Treatment Outcome

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Insulin Glargine