Favorable pleiotropic effects of sodium glucose cotransporter 2 inhibitors: head-to-head comparisons with dipeptidyl peptidase-4 inhibitors in type 2 diabetes patients

Abstract

Background: Sodium glucose cotransporter 2 (SGLT2) inhibitors have shown greater reductions of cardiovascular event risks than dipeptidyl peptidase-4 (DPP4) inhibitors, whereby possible mechanisms may involve the better pleiotropic effects of SGLT2 inhibitors. However, no published data are currently available to directly compare glycemic and pleiotropic effects in real-world type 2 diabetes patients initiating SGLT2 inhibitors or DPP4 inhibitors. Method: We conducted a retrospective cohort study by analyzing the Chang Gung Research Database, the largest multi-institutional electronic medical records database in Taiwan. We included patients newly receiving SGLT2 inhibitor or DPP4 inhibitor intensification therapy for type 2 diabetes from 2016 to 2017. We matched SGLT2 inhibitor users to DPP4 inhibitor users (1:4) by propensity scores to ensure comparable characteristics between the groups. We primarily evaluated 1-year post-treatment changes of hemoglobin A1c (HbA1c) after SGLT2 inhibitor or DPP4 inhibitor initiation, using two-tailed independent t-test. We also evaluated post-treatment changes in body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values, associated with SGLT2 inhibitors and DPP4 inhibitors. Results: We identified a cohort of 2028 SGLT2 inhibitors and 8112 matched DPP4 inhibitors new users. SGLT2 inhibitors and DPP4 inhibitors showed similar HbA1c reductions (− 1.0 vs. − 1.1%; P = 0.076), but patients receiving SGLT2 inhibitors had greater improvements in body weight (− 1.5 vs. − 1.0 kg; P = 0.008), SBP (− 2.5 vs. − 0.7 mmHg; P < 0.001) and ALT values (− 4.1 vs. − 0.0 U/l; P < 0.001) and smaller declines in eGFR values (− 2.0 vs. − 3.5 ml/ min/1.73 m 2 ; P < 0.001) when compared to DPP4 inhibitors. Conclusion: SGLT2 inhibitors had glucose-lowering effects comparable to those of DPP4 inhibitors but more favorable pleiotropic effects on body weight, ALT and eGFR changes, potentially improving type 2 diabetes patients' cardiometabolic disease risks.

The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors

“…SGTL2i has been shown to reduce blood sugar levels, blood pressure, body weight, albuminuria, lipid profile, arterial stiffness, and endothelial function via an insulin-independent mechanism in T2DM patients [ 32 ]. Recent study indicated that SGLT2i had more favorable pleiotropic effects on body weight, liver function and eGFR changes when compared to DPP4i, potentially modifying the cardio-metabolic disease risks in T2DM patients [ 33 ]. Moreover, SGLT2i has been shown to have impressive cardioprotective and renoprotective effects.…”

“…We choose the DPP4i as an active comparator because it is a relatively new and widely used anti-hypoglycemic agent until now. Also, several important studies have used the DPP4i as the comparator [ 19 , 33 , 44 , 45 ]. There are several limitations to the present study.…”

The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors

“…[32] Recent study indicated that SGLT2i had more favorable pleiotropic effects on body weight, liver function and eGFR changes when compared to DPP4i, potentially modifying the cardio-metabolic disease risks in T2DM patients. [33] Moreover, SGLT2i has been shown to have impressive cardioprotective and renoprotective effects. The main mechanisms of their cardioprotective effects are improvements in cardiac cell metabolism and ventricular loading conditions, inhibition of Na + /H + exchange in myocardial cells, alterations in adipokine and cytokine production, and reductions in cardiac cell necrosis and cardiac brosis.…”

“…Also, several important studies have used the DPP4i as the comparator. [19,33,44,45] There are several limitations to the present study. First, we did not have serial ECG data to help identify whether the patients diagnosed with AF had persistent or paroxysmal AF related to acute illnesses such as hyperthyroidism or infection.…”

Comparative effectiveness of dulaglutide versus liraglutide in Asian type 2 diabetes patients: a multi-institutional cohort study and meta-analysis

“…It comprises de-identi ed individual EMRs of disease diagnoses, medical visits (outpatient, inpatient, and emergency room), pharmacy records, examination reports, and laboratory data from seven medical institutes throughout Taiwan, covering 1.3 million individuals (about 6% of Taiwan's total population) [16]. Its validity for real-world pharmacoepidemiological studies is documented elsewhere [16][17][18][19][20].…”