Renoprotective effect of additional sodium-glucose cotransporter 2 inhibitor therapy in type 2 diabetes patients with rapid decline and preserved renal function.

AIMS/INTRODUCTION: The slope of estimated glomerular filtration rate (eGFR) decline (eGFR slope) in early-stage type 2 diabetes patients might predict the future risk of end-stage renal disease. Type 2 diabetes patients who show rapid progressive eGFR decline are termed rapid decliners. Several studies of rapid decliners have investigated the efficacy of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in patients with advanced renal dysfunction; however, no studies, to our knowledge, have focused on patients with preserved renal function. Therefore, we investigated the efficacy of SGLT2i in rapid decliners with preserved renal function. MATERIALS AND METHODS: This study enrolled type 2 diabetes patients with baseline eGFR ≥60 mL/min/1.73 m2 who had been treated with SGLT2i for ≥3 years. Among these individuals, we defined those with annual eGFR declines ≥5 mL/min/1.73 m2 per year before SGLT2i administration as rapid decliners. The primary end-point was the change in eGFR slope after SGLT2i administration. RESULTS: Among 165 patients treated with SGLT2i for ≥3 years, 21 patients were rapid decliners with preserved renal function. The mean age and eGFR at SGLT2i administration were 58.6 years and 87.1 mL/min/1.73 m2 , respectively. The mean annual eGFR slope improved significantly in those administered SGLT2i compared with the control group (-1.00 and -4.36 mL/min/1.73 m2 per year, respectively; P < 0.001). Notably, the steeper the eGFR slope before starting SGLT2i administration, the larger the improvement of eGFR slope, which was independent of the reduction of albuminuria. CONCLUSIONS: Early intervention with SGLT2i may have renoprotective effects in type 2 diabetes patients with rapid decline and preserved renal function.

COPD biomarkers as tools for decision making in early clinical drug development.

In this perspective article, we discuss, from a statistician's perspective, how biomarkers can be useful in decision making in drug development with emphasis on early clinical development (Phase I and II) in chronic obstructive pulmonary disease. We illustrate with examples of how biomarkers can affect the very choice of treatment strategy: for example, targeting patients in early versus late phases of the disease or patients with particular extrapulmonary manifestations of chronic obstructive pulmonary disease. We also illustrate the use of biomarkers for establishing proof of mechanism in Phase I trials and how surrogate biomarkers can be used as end points in Phase II leading to shorter and more efficient proof-of-principle and dose-finding trials.