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Abstract
BackgroundSodium 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.MethodWe 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.ResultsWe 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 m2; P < 0.001) when compared to DPP4 inhibitors.ConclusionSGLT2 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’ cardio-metabolic disease risks.
Highlights
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 pleio‐ tropic effects of SGLT2 inhibitors
We identified a total of 19,148 patients who initiated SGLT2 inhibitors or DPP4 inhibitors based on study inclusion and exclusion criteria (Fig. 1)
We found the effects on body weight, systolic blood pressure (SBP), alanine aminotransferase (ALT) and estimated glomerular filtration rate (eGFR) values were better in SGLT2 inhibitors than DPP4 inhibitors throughout a series of subgroup analyses with hemoglobin A1c (HbA1c) > 7 or ≤ 7%, ALT > 1× or ≤ 1× upper limit of normal (ULN), with or without a history of treatment failures of > 1 anti-diabetes medications, and with body mass index (BMI) ≥ 27 kg/ m2 or < 27 kg/m2
Summary
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 pleio‐ tropic effects of SGLT2 inhibitors. Several new drugs of different therapeutic classes have been introduced into diabetes treatment, but the use of sodium glucose cotransporter 2 (SGLT2) inhibitors and dipeptidyl peptidase-4 (DPP4) inhibitors has increased substantially [6], possibly because of their favorable side effect profiles. Meta-analyses of clinical trials have found SGLT2 inhibitors bring similar improvement in HbA1c, but better reductions of body weight and systolic blood pressure (SBP) compared to DPP4 inhibitors [11, 12]. Several individual clinical trials have indicated SGLT2 inhibitors show better improvements in alanine aminotransferase (ALT) values and delayed declines of estimated glomerular filtration rate (eGFR) values when compared to DPP4 inhibitors [13, 14]
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