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

• DOI: 10.1016/j.diabres.2022.110012
• Publication Date: 2022-07-18T15:45:06Z
• Authors: Wolfgang Landgraf; Gregory Bigot; Sibylle Hess; Olof Asplund; Leif Groop; Emma Ahlqvist; Annemari Käräjämäki; David R. Owens; Brian M. Frier; Geremia B. Bolli
• Keywords: C -peptide; 330; 610; THERAPY; Randomised clinical trial; Diabetes Complications; HYPOGLYCEMIA; 03 medical and health sciences; 0302 clinical medicine; NAIVE PEOPLE; Humans; Insulin; INSULIN GLUCOSE CONTROL; GLARGINE 100 UNITS/ML; Randomized Controlled Trials as Topic; Glycated Hemoglobin; Type 2 diabetes; Fasting; ta3121; 16. Peace & justice; General medicine, internal medicine and other clinical medicine; 3. Good health; NPH INSULIN; ORAL-AGENTS; TO-TARGET TRIAL; PLUS METFORMIN; Diabetes Mellitus, Type 2; Cluster; Hyperglycemia; Real -world studies; C-peptide; BASAL INSULIN; Real-world studies

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).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.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.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.