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Lee, Moon, Han, Shin, Baek, Han, Cho, and Kim: The Effect and Safety of Dapagliflozin in Patients with Type 2 Diabetes: A Single-Institution Pharmacovigilance Review
Original Article

J Korean Diabetes 2017;18(4):275-283.

Published online: 10 January 2017

DOI: https://doi.org/10.4093/jkd.2017.18.4.275

The Effect and Safety of Dapagliflozin in Patients with Type 2 Diabetes: A Single-Institution Pharmacovigilance Review

Hyung Woo Lee1, Sun Joon Moon2, Hee Sim Han1, Eun Jeong Shin1, Jin Hee Baek1, Hyun-Joo Han1, Young Min Cho2, Kwi Suk Kim1

1Department of Pharmacy, Seoul National University Hospital, Seoul, Korea

2Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea

Corresponding author: Kwi Suk Kim Department of Pharmacy, Seoul National University Hospital, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea, E-mail: kimks@snuh.org

Received 8 March 2017       Revised 5 April 2017       Accepted 11 December 2017

Copyright © 2017 Korean Diabetes Association

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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).

Conclusion

Dapagliflozin significantly improved hyperglycemia in patients with type 2 diabetes without serious adverse drug events. The incidences of adverse drug events were was similar to those ofthat in the previous studies.

Keywords: Dapagliflozin, Diabetes mellitus, Risk factors, Sodium-glucose co-transporter 2 inhibitor

References

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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.

a Data are mean baseline ± standard deviation (SD) and mean change at the 2nd visit ± standard error.

b Data are mean days between 1st to 2nd visits ± SD.

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

HR, hazzard ratio; CI, confidence interval; N/A, not available.

a Age was analyzed as a categorical variable here, while it was analyzed as a continuous variable elsewhere.

b Insulin is not included in this variable.

c Because the urogenital infection group comprised only women, logistic regression data for sex was not available.

Table 3.
The adverse effects of diabetes drugs used
Combination Types No. of patient Sum of side effects Side effects
Hypoglycemia Infection Urogenital symptoms Ketonuria Dehydration Other
1 P 7 9 1 1 3 1 2 1
2 P + I 3 5 0 0 2 0 2 1
P + M 9 12 0 3 2 0 5 2
P + A 1 1 0 0 0 0 0 1
3 P + M + D 8 10 1 1 3 4 1 0
P + M + I 10 12 4 2 2 2 2 0
P + M + S 22 27 1 3 10 3 7 3
4 P + M + S + A 2 3 1 1 0 0 1 0
P + M + S + D 9 15 3 2 6 1 2 1
P + M + S + I 7 7 1 3 1 2 0 0
P + M + T + D 2 3 1 0 0 0 1 1
Sum 80 104 13 16 29 13 23 10

P, dapagliflozin; I, insulin; M, metformin; A, α-glucosidase inhibitor; D, DPP4 inhibitor; S, sulfonylurea; T, thiazolidinedione.

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