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Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials : Post hoc cluster assignment analysis of over 12,000 study participants

Landgraf, Wolfgang ; Bigot, Gregory ; Hess, Sibylle ; Asplund, Olof LU ; Groop, Leif LU ; Ahlqvist, Emma LU ; Käräjämäki, Annemari ; Owens, David R. ; Frier, Brian M. and Bolli, Geremia B. (2022) In Diabetes Research and Clinical Practice 190.
Abstract

Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and... (More)

Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration > 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m2. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.

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author
; ; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
C-peptide, Cluster, Randomised clinical trial, Real-world studies, Type 2 diabetes, ANDIS, diabetes
in
Diabetes Research and Clinical Practice
volume
190
article number
110012
publisher
Elsevier
external identifiers
  • pmid:35863553
  • scopus:85134646102
ISSN
0168-8227
DOI
10.1016/j.diabres.2022.110012
language
English
LU publication?
yes
id
7bb7da91-14a5-4e41-9edb-520d2207b455
date added to LUP
2022-09-27 16:41:13
date last changed
2025-03-09 01:53:07
@article{7bb7da91-14a5-4e41-9edb-520d2207b455,
  abstract     = {{<p>Aims: Newly-defined subgroups of type 2 diabetes mellitus (T2DM) have been reported from real-world cohorts but not in detail from randomised clinical trials (RCTs). Methods: T2DM participants, uncontrolled on different pre-study therapies (n = 12.738; 82 % Caucasian; 44 % with diabetes duration &gt; 10 years) from 14 RCTs, were assigned to new subgroups according to age at onset of diabetes, HbA1c, BMI, and fasting C-peptide using the nearest centroid approach. Subgroup distribution, characteristics and influencing factors were analysed. Results: In both, pooled and single RCTs, “mild-obesity related diabetes” predominated (45 %) with mean BMI of 35 kg/m<sup>2</sup>. “Severe insulin-resistant diabetes” was found least often (4.6 %) and prevalence of “mild age-related diabetes” (23.9 %) was mainly influenced by age at onset of diabetes and age cut-offs. Subgroup characteristics were widely comparable to those from real-world cohorts, but all subgroups showed higher frequencies of diabetes-related complications which were associated with longer diabetes duration. A high proportion of “severe insulin-deficient diabetes” (25.4 %) was identified with poor pre-study glycaemic control. Conclusions: Classification of RCT participants into newly-defined diabetes subgroups revealed the existence of a heterogeneous population of T2DM. For future RCTs, subgroup-based randomisation of T2DM will better define the target population and relevance of the outcomes by avoiding clinical heterogeneity.</p>}},
  author       = {{Landgraf, Wolfgang and Bigot, Gregory and Hess, Sibylle and Asplund, Olof and Groop, Leif and Ahlqvist, Emma and Käräjämäki, Annemari and Owens, David R. and Frier, Brian M. and Bolli, Geremia B.}},
  issn         = {{0168-8227}},
  keywords     = {{C-peptide; Cluster; Randomised clinical trial; Real-world studies; Type 2 diabetes; ANDIS; diabetes}},
  language     = {{eng}},
  publisher    = {{Elsevier}},
  series       = {{Diabetes Research and Clinical Practice}},
  title        = {{Distribution and characteristics of newly-defined subgroups of type 2 diabetes in randomised clinical trials : Post hoc cluster assignment analysis of over 12,000 study participants}},
  url          = {{http://dx.doi.org/10.1016/j.diabres.2022.110012}},
  doi          = {{10.1016/j.diabres.2022.110012}},
  volume       = {{190}},
  year         = {{2022}},
}