Cardioprotective therapy in type 2 diabetes guided by a proteomic risk model: A randomized trial

Figures

• 

  Fig. 1. Central Illustration: Proteomic risk disclosure aligns therapy with risk and detects change: Cardioprotective (CP) therapies remain underused in patients with type 2 diabetes (T2D). In a multi-center, randomized trial, adults with T2D were randomized to RCVR informed (results disclosed to participants and HCPs after baseline clinical visit) vs. uninformed (RCVR results withheld until end of study) arms. CP prescribing was higher with disclosure (32.1 % vs 9.6 %; OR 5.45, 95 % CI 2.31–12.89; p < 0.001), consistent with risk-aligned treatment. Among informed participants who initiated CP therapy, RCVR decreased 3.9 % from baseline to follow-up (6-12 months) (p = 0.036). Findings support proteomic-guided, risk-aligned prescribing and early risk reduction.

• 

  Fig. 2. Trial flow and participant disposition. Participant flow through the multicenter randomized controlled trial evaluating the SomaSignal Residual Cardiovascular Risk (RCVR) test to guide cardioprotective (CP) medication prescribing in adults with type 2 diabetes (T2D). Randomization: Of 9,730 individuals screened across three academic sites, 395 were randomized in site-specific ratios (CU Anschutz 1:1; Emory 1:1; UHCMC 2:1) to an informed arm (clinicians received RCVR results) or an uninformed arm (RCVR results withheld until end of study). Allocation: Informed n = 233 (CU Anschutz 58; Emory 72; UHCMC 103) and uninformed n = 162 (CU Anschutz 40; Emory 71; UHCMC 51). Follow-up (6–12 months): Follow-up completed for 97 informed (CU Anschutz 44; Emory 53) and 89 uninformed (CU Anschutz 38; Emory 51). Attrition: Excluding UHCMC (baseline-only by protocol), attrition from follow-up was 33/130 in the informed arm (CU Anschutz 14; Emory 19) and 22/111 in the uninformed arm (CU Anschutz 2; Emory 20), primarily due to early study termination or missed visits. Primary outcome (CP therapy prescribing): Analyzed n=221 informed and n=156 uninformed; excluded for missing RCVR and/or CP data: 12…

• 

  Fig. 3. Cardioprotective (CP) medication prescribing rate by RCVR Relative Risk Bin: Rate of CP prescribing (Y/Total N per bin) with 95 % CI bands, compared by RCVR relative risk bin (Low Risk: 0-7.5 %, Medium-Low Risk: 7.6-25 %, Medium-High Risk: 26 %-50 %, and High Risk: 51 %-100 % risk of a CV event within 4 years) and trial arm. Prescribing rates significantly (one-sided equality of proportions, p<0.05) higher in informed arm compared to uninformed for all elevated risk bins. Significance of proportionality trend test across risk bins within arms shown, suggesting increasing trend in informed arm only.

• 

  Fig. 4. Change in RCVR in Informed Participants, Grouped by CP Initiation: Data points are colored by RCVR relative risk category at baseline (Low Risk: 0-7.5 %, Medium-Low Risk: 7.6-25 %, Medium-High Risk: 26 %-50 %, and High Risk: 51 %-100 % risk of a CV event within 4 years) and connected within subject over time by grey lines. Mean (large red dot) RCVR from baseline to 6-months in participants who did not start CP medication after baseline visit (n = 68) increased (black trend line) 0.9 % (p=0.771), while mean RCVR decreased by 3.9 % in participants who initiated CP treatment (p=0.036). Results suggest that RCVR decrease reflects reduced CV risk following initiation of CP medication.

• 

  Fig. 5. Distribution of change in cardiovascular risk scores by study arm and CP medication status. Boxplots show changes from Baseline to 6-12 months in ASCVD risk score (red) and Residual Cardiovascular Risk (RCVR) score (blue) across four groups: Informed arm participants who started CP medications (Informed + CP), informed arm participants who did not start CP medications (Informed + No CP), uninformed arm participants who started (Uninformed + CP) and did not start (Uninformed + No CP) medications. The box center line denotes the median, boxes represent the interquartile range (IQR), whiskers extend to 1.5*IQR, and individual points indicate outliers. The dashed horizontal line at zero represents no change in risk score. RCVR scores decreased significantly in the informed participants who started CP medications (-3.92, p=0.036). ASCVD scores increased significantly in Informed + CP (1.57, p=0.031) and Uninformed + No CP (1.67, p = 0.008) groups.