Abstract
Background
Dapagliflozin, a selective sodium-glucose co-transporter 2 (SGLT2) inhibitor, lowers blood glucose by reducing glucose reabsorption at the proximal renal tubule in an insulin-independent manner. We aimed to evaluate the efficacy and safety of dapagliflozin and to identify the risk factors of adverse drug events in patients with type 2 diabetes.
Methods
As an institutional pharmacovigilance review activity, we reviewed data from medical records of 455 patients with type 2 diabetes who received dapagliflozin therapy from July 2014 to August 2015 in Seoul National University Hospital. We analyzed the changes in laboratory data and examined the characteristics of dapagliflozin users who showed adverse effects.
Results
Mean changes in HbA1c and fasting serum glucose level from baseline to second visit were –0.42% (8.07 ± 1.51% to 7.65 ± 1.31%, P < 0.001) and –22.9 mg/dL (167.8 ± 48.5 mg/dL to 144.9 ± 37.6 mg/dL, P < 0.001), respectively. Adverse drug events observed during this study were lower urinary tract symptoms (7.7%), dehydration-related symptoms (6.1%), ketonuria (3.4%), hypoglycemia (3.4%), and urogenital infection (4.2%). Thiazide use, age, insulin use, number of anti-diabetic drugs, gender and history of urogenital infection were the risk factors for adverse drug events (P < 0.05).
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Table 1.
Changes in variables from baseline to the second visit
Variable | N | Baselinea | Mean change at 2nd visita | Mean days to 2nd visitb | P-value |
---|---|---|---|---|---|
HbA1C (%) | 301 | 8.07 ± 1.51 | –0.42 ± 0.05 | 64.6 ± 29.9 | < 0.001 |
FBS (mg/dL) | 197 | 167.75 ± 48.46 | –22.90 ± 3.70 | 63.2 ± 29.2 | < 0.001 |
SBP (mmHg) | 284 | 129.10 ± 15.05 | –2.94 ± 0.82 | 64.3 ± 32.2 | < 0.001 |
DBP (mmHg) | 284 | 77.09 ± 9.56 | –1.31 ± 0.54 | 64.3 ± 32.2 | 0.016 |
Uric acid (mg/dL) | 155 | 6.60 ± 12.35 | –0.12 ± 0.10 | 64.8 ± 31.2 | 0.196 |
Triglycerides (mg/dL) | 117 | 165.12 ± 95.77 | –6.02 ± 8.76 | 70.6 ± 30.8 | 0.493 |
Total cholesterol (mg/dL) | 170 | 159.31 ± 35.22 | –0.23 ± 2.13 | 65.7 ± 31.0 | 0.915 |
HDL-C (mg/dL) | 117 | 48.27 ± 11.80 | 1.03 ± 0.60 | 70.6 ± 30.8 | 0.089 |
LDL-C (mg/dL) | 111 | 88.57 ± 28.44 | –2.45 ± 2.56 | 69.7 ± 29.2 | 0.340 |
Creatinine (mg/dL) | 150 | 0.92 ± 0.26 | 0 ± 0.01 | 64.1 ± 31.3 | 0.994 |
GFR (mL/min/1.73 m2) | 150 | 81.29 ± 19.92 | 0.49 ± 0.91 | 64.1 ± 31.3 | 0.592 |
AST (IU/L) | 158 | 31.42 ± 22.26 | –2.67 ± 1.20 | 64.9 ± 31.3 | 0.028 |
ALT (IU/L) | 158 | 37.38 ± 25.93 | –5.58 ± 1.24 | 64.9 ± 31.3 | < 0.001 |
Total bilirubin (mg/dL) | 152 | 0.78 ± 0.35 | 0 ± 0.02 | 64.3 ± 31.1 | 0.841 |
FBS, fasting blood sugar; SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL-C, high density lipoprotein cholesterol; LDL-C, low density lipoprotein cholesterol; GFR, glomerular filtration rate; AST, aspartate aminotransferase; ALT, alanine aminotransferase.
Table 2.
Multivariable logistic regression analysis of the risk for adverse effects in patients with diabetes under treatment with dapagliflozin
Risk for adverse effects | HR (95% CI) | P-value |
---|---|---|
Dehydration-related symptoms | ||
Gender (male/female) | 1.019 (0.417∼2.493) | 0.967 |
Age (< 65 years)a | 3.394 (1.102∼10.459) | 0.033 |
Number of anti-diabetic drugs | 0.885 (0.561∼1.397) | 0.601 |
Thiazide use | 2.452 (0.953∼6.311) | 0.063 |
Hypoglycemia | ||
Gender (male/female) | 1.045 (0.318∼3.432) | 0.942 |
Age | 0.983 (0.936∼1.033) | 0.507 |
Number of anti-diabetic drugs | 2.086 (1.027∼4.236) | 0.042 |
Thiazide use | 1.499 (0.387∼5.816) | 0.558 |
Ketonuria | ||
Gender (male/female) | 1.125 (0.344∼3.678) | 0.845 |
Age | 0.982 (0.934∼1.033) | 0.482 |
Number of anti-diabetic drugsb | 1.152 (0.590∼2.248) | 0.679 |
Thiazide use | 0.378 (0.047∼3.053) | 0.362 |
Insulin use | 4.408 (1.218∼15.958) | 0.024 |
Lower urinary tract symptoms | ||
Gender (male/female) | 1.364 (0.597∼3.118) | 0.461 |
Age | 0.978 (0.946∼1.012) | 0.208 |
Number of anti-diabetic drugs | 1.192 (0.778∼1.826) | 0.420 |
Thiazide use | 2.539 (1.080∼5.968) | 0.033 |
Urogenital infection | ||
Gender (male/female) | N/Ac | N/Ac |
Age | 1.108 (0.959∼1.280) | 0.165 |
Number of anti-diabetic drugs | 1.963 (0.480∼8.029) | 0.348 |
History of urogenital infection | 743.288 (12.137∼45,521.745) | 0.002 |
Thiazide use | 6.715 (0.539∼83.719) | 0.139 |
Table 3.
The adverse effects of diabetes drugs used