(83) Comparative Effectiveness of First-Line SGLT2 Inhibitor Use on Heart Failure Hospitalization Among Patients with Type 2 Diabetes Mellitus; A Target Trial Emulation

Publication Number: 757

Background: Preferred pharmacotherapy for patients with diabetes mellitus (DM) have changed in recent years. While recommendations for first-line pharmacologic therapy for those with or at risk of cardiovascular comorbidities have been updated to include Sodium-glucose cotransporter 2 (SGLT2) inhibitor use, the evidence on its comparative effectiveness for treatment initiators remains scarce. Japanese clinical practice guidelines have not recommended specific pharmacotherapy for DM in recent years, and non-biguanide agents are frequently prescribed as an initial agent.

Objectives: To evaluate the comparative effectiveness of first-line SGLT2 inhibitor use on H-hf among treatment naïve Japanese type-2 DM patients against biguanide or dipeptidyl peptidase 4 (DPP-4) inhibitors.

Methods: We used the Japanese nationwide claims database to extract patients with type2 DM diagnosis newly initiating biguanide, DPP4i or SGLT2i in fiscal year 2014. Those with previous DM drug use or history of heart failure were excluded. To extract similar number of patients in each treatment group, and for the ease of computation, we randomly sampled 100% of SGLT2i, 20% of biguanide, and 3% of DPP4i initiators from the cohort. We followed the patients up to 1080 days after the initiation, and assessed the incidence of H-hf. We used inverse probability of treatment weighting to adjust for baseline characteristics including age, sex, comorbidities, other medication use and hospitalization history, and inverse probability of censoring weighting for per-protocol effect estimation adjusting for the same variables assessed every 90-days. Weighted Kaplan Meier method was used to estimate 3-year cumulative incidence of hf-H, and weighted Cox model was used for hazard ratio estimation.

Results: We extracted 7288 biguanide-, 10,687 DPP4 inhibitor-, and 8976 SGLT2 inhibitor-initiators with mean age (standard deviation) of 60.6 (10.9), 66.9 (11.5), and 57.5 (10.9), respectively. Among them, 894 (12.3%), 1755 (22.4%) and 1272 (22.8%) of the patients, respectively, were previously diagnosed to have coronary artery disease. While the crude 3-year cumulative H-hf incidences were 1.0%, 1.9% and 0.5%, weighted ITT incidence estimates were 1.5%, 1.7% and 1.0%, and weighted per-protocol estimates were 1.2%, 1.4% and 0.8%, respectively. ITT hazard ratios (HR) estimates and 95% confidence intervals were 1.17 (0.89-1.54) for DPP4 inhibitors and 0.68 (0.47-1.00) for SGLT2 inhibitors compared to biguanides, while per-protocol HRs were 1.06 (0.70-1.63), and 0.49 (0.25-0.94) respectively.

Conclusions: First-line SGLT2 inhibitor use may reduce the hazard of H-hf compared to biguanide in routine care.