TABLE 1.
Effects of ertugliflozin on biomarkers that may mediate the effects of ertugliflozin on hospitalization for heart failure or composite kidney outcomes
| Mean (SD) at baseline | Placebo-adjusted change from baseline (least squares mean [95% CI]) | |||
|---|---|---|---|---|
| Placebo (n = 2747) |
Ertugliflozin (n = 5499) |
Early | Average | |
| Glycaemia | ||||
| HbA1c, % | 8.2 (0.9) | 8.2 (1.0) | −0.46 (−0.49, −0.42) | −0.44 (−0.48. −0.40) |
| Fasting plasma glucose, mmol/L | 9.6 (2.7) | 9.7 (2.9) | −1.31 (−1.43, −1.19) | −1.07 (−1.16, −0.99) |
| Vascular | ||||
| SBP, mmHg | 133.1 (13.9) | 133.5 (13.7) | −2.85 (−3.47, −2.23) | −2.60 (−3.03, −2.16) |
| DBP, mmHg | 76.4 (8.7) | 76.8 (8.3) | −0.94 (−1.31, −0.56) | −0.86 (−1.13, −0.59) |
| Heart rate, bpm | 70.6 (10.1) | 70.8 (10.1) | −0.07 (−0.45, 0.31) | −0.38 (−0.67, −0.10) |
| Lipids | ||||
| LDL-C, mmol/L | 2.3 (1.0) | 2.3 (1.0) | 0.06 (0.02, 0.10) | 0.07 (0.03, 0.10) |
| HDL-C, mmol/L | 1.1 (0.3) | 1.1 (0.3) | 0.03 (0.02, 0.04) | 0.04 (0.03, 0.05) |
| LDL/HDL ratio | 2.1 (1.0) | 2.1 (1.0) | −0.01 (−0.05, 0.03) | −0.01 (−0.04, 0.02) |
| Triglycerides, mg/dL | 178.9 (104.7) | 181.4 (119.2) | −1.98 (−6.98, 3.03) | 0.51 (−3.30, 4.32) |
| Renal | ||||
| UACR, mg/g (median [IQR])† | 19.0 (6.0–66.5) | 18.0 (6.0–69.0) | −0.08 (−0.10, −0.05) | −0.09 (−0.11, −0.07) |
| eGFR, mL/min/1.73 m2 (MDRD) | 75.7 (20.8) | 76.1 (20.9) | −2.77 (−3.33, −2.21) | −1.32 (−1.79, −0.86) |
| Adiposity | ||||
| Weight, kg | 91.9 (18.3) | 91.7 (18.5) | −1.10 (−1.21, −1.00) | −2.07 (−2.25, −1.89) |
| Volume status and haematopoiesis | ||||
| Haematocrit, % | 42.9 (4.1) | 43.1 (4.1) | 1.70 (1.57, 1.83) | 2.14 (2.03, 2.26) |
| Haemoglobin, g/dL | 14.0 (1.4) | 14.0 (1.4) | 0.45 (0.41, 0.49) | 0.58 (0.54, 0.61) |
| Serum albumin, g/dL | 4.4 (0.3) | 4.4 (0.3) | 0.06 (0.05, 0.07) | 0.05 (0.04, 0.06) |
| Red blood cell count (106/μL) | 4.7 (0.5) | 4.8 (0.5) | 0.17 (0.15, 0.18) | 0.23 (0.21, 0.24) |
| Indicators of acidosis/alkalosis | ||||
| Serum bicarbonate, mEq/L | 24.4 (2.6) | 24.5 (2.5) | −0.59 (−0.71, −0.47) | −0.38 (−0.46, −0.30) |
| Other | ||||
| Urate, mg/dL | 5.7 (1.6) | 5.6 (1.6) | −0.34 (−0.39, −0.29) | −0.37 (−0.41, −0.32) |
| Sodium, mEq/L | 141.2 (2.7) | 141.1 (2.7) | 0.43 (0.31, 0.55) | 0.39 (0.31, 0.47) |
| Chloride, mmol/L | 100.4 (3.0) | 100.3 (3.0) | 0.57 (0.43, 0.71) | 0.40 (0.31, 0.49) |
| Magnesium, mEq/L | 1.5 (0.2) | 1.5 (0.2) | 0.15 (0.15, 0.16) | 0.15 (0.14, 0.15) |
| Phosphate, mg/dL | 3.5 (0.5) | 3.5 (0.5) | 0.18 (0.15, 0.20) | 0.14 (0.12, 0.15) |
| Protein, g/dL | 7.1 (0.4) | 7.1 (0.5) | 0.09 (0.08, 0.11) | 0.08 (0.06, 0.09) |
| BUN, mg/dL | 18.4 (6.7) | 18.2 (6.4) | 1.19 (0.93, 1.45) | 1.11 (0.93, 1.29) |
| ALT, IU/L | 25.1 (18.6) | 25.2 (17.5) | −0.64 (−1.28, 0.00) | −1.22 (−1.65, −0.79) |
| AST, IU/L | 21.4 (11.1) | 21.5 (19.9) | 0.09 (−0.46, 0.64) | −0.62 (−171.61, 170.38) |
Values in bold indicate a significant treatment effect (P < .05). Early change model adjusted by treatment, baseline value of outcome variable, baseline UACR, baseline eGFR, baseline BMI, and baseline SBP. Average change model is a mixed-model repeated-measures analysis using all available data from patients who had baseline and follow-up measurement for the respective outcome. The model adjusted for baseline of outcome variable, baseline UACR, baseline eGFR, baseline BMI, and baseline SBP.
The placebo-adjusted changes from baseline values are based on log-transformed data.
ALT, alanine aminotransferase; AST, aspartate aminotransferase; BMI, body mass index; BUN, blood urea nitrogen; DBP, diastolic blood pressure; eGFR, estimated glomerular filtration rate; HbA1c, glycated haemoglobin; HDL-C, high-density lipoprotein cholesterol; IQR, inter-quartile range; LDL-C, low-density lipoprotein cholesterol; MDRD, Modification of Diet in Renal Disease; SBP, systolic blood pressure, UACR, urine albumin-to-creatinine ratio.