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. (August 2022)

• Record Type: Journal Article
• Authors: Landgraf, Wolfgang; Bigot, Gregory; Hess, Sibylle; Asplund, Olof; Groop, Leif; Ahlqvist, Emma; Käräjämäki, Annemari; Owens, David R.; Frier, Brian M.; Bolli, Geremia B.
• Is Part Of: Diabetes research and clinical practice. Volume 190(2022)
• Publication Date: 2022-08
• Subjects: Cluster -- C-peptide -- Type 2 diabetes -- Randomised clinical trial -- Real-world studies; Diabetes -- Periodicals; Diabetes Mellitus -- Periodicals; 616.462
• DOI: 10.1016/j.diabres.2022.110012
• Languages: English
• ISSNs: 0168-8227

Abstract

Highlights: Distribution of newly-defined diabetes subgroups in randomised clinical trials (RCTs) is unknown. Mild obesity-related diabetes (MOD) was the predominant subgroup in a set of both pooled and single T2DM RCTs. Severe insulin-deficient diabetes (SIRD) subgroup was least prevalent in RCTs. Diabetes duration is a strong modifying factor of subgroup distribution and characteristics. Subgroup-based randomisation in future RCTs may better define the target T2DM population by avoiding clinical heterogeneity. 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/m 2 . " 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.