867-P: Cardiovascular Outcomes in Patients Initiating a Second Diabetes Medication after Metformin—The BESTMED Study

Introduction: In patients with T2D at high cardiovascular (CV) risk, several classes of medications have been found to reduce incidence of CV events. However, long-term CV outcomes of T2D medications in lower risk patients are unknown.

Methods: We conducted a causal inference study by emulating a target trial using observational data from 12 health systems and insurance plans across the US. Eligible individuals were patients with T2D and hyperglycemia (HbA1c 7.0-11.0% or equivalent glucose levels) at moderate CV risk (no CV disease) on metformin monotherapy who initiated a second T2D medication between 01/01/13 and 09/01/21, with eGFR ≥ 45 ml/min/1.73m² and with no contraindications to study medications. We compared patients initiating one of the following medication classes: DPP4s, GLP1s, SGLT2s and sulfonylureas (SUs). In each treatment arm we estimated the 5-year risk of a composite outcome (MI, ischemic CVA, HF hospitalization or CV death) after adjustment for demographics, comorbidities and laboratory values at baseline.

Results: We studied 55,441 patients followed for a median of 32 (IQR 18-54) months, with a median age of 60 (IQR 52-68) years and median baseline HbA1c of 7.8% (IQR 7.3-8.6%). Of these, 11,195 patients initiated a DPP4, 6,920 a GLP1, 7,911 an SGLT2 and 29,415 an SU; 40,673 (73.4)% of patients stopped the original study drug class before the end of follow-up after a median of 11 (IQR 3-22) months. A total of 2,566 (4.6%) of patients experienced the primary outcome endpoint. The estimated 5-year risk ratios (95% CI), compared to DPP4s, were 0.93 (0.73 - 1.13) for GLP1s, 0.96 (0.83 - 1.14) for SGLT2s and 1.08 (0.98 - 1.19) for SUs.

Conclusions: Among patients with T2D at moderate CV risk on metformin monotherapy, incidence of CV events was similar among four classes of most commonly used non-insulin T2D medications. Further research is needed to evaluate the risk of non-CV events to help patients and clinicians to make informed decisions on T2D therapy.