• Korean Journal of Clinical Pharmacy
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• v.27 no.4
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• pp.214-220
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• 2017

Background: Dapagliflozin is an oral selective inhibitor of sodium-glucose cotransporter 2(SGLT2), the kidney transporter chiefly responsible for glucose reabsorption from the glomerular filtrate. Because this mechanism does not require the action of insulin, dapagliflozin rarely causes hypoglycemia. Dapagliflozin may affect blood glucose control as well as blood pressure and the body weight which are one of the cardiovascular disease risk factors. However, dehydration and ketoacidosis are reported as the side effects of the dapagliflozin treatment and the safety issues have been occurred. The aim of this study is to analyze the effectiveness and adverse events of dapagliflozin in Korean patients. Methods: From December 2014 to August 2015, we retrospectively reviewed the electronic medical records of type 2 diabetes patients who were prescribed dapagliflozin at Severance Hospital. Results: A total of 202 Korean patients were enrolled in this study. The effectiveness in the reduction of blood glucose was statistically significant(p<0.001). Dapagliflozin decreased 0.74% of HbA1c after 24 weeks. Significantly more participants achieved the target HbA1c level(HbA1c<7%) after 24 weeks(n=42, 35.3%) than before taking dapagliflozin(n=21, 17.6%). Blood pressure decreased 5.7 mmHg systolic blood pressure(SBP), 1.9 mmHg diastolic blood pressure(DBP) after 24 weeks. More than one quarter of participants(n=35, 29.4%) experienced weight loss. Most common adverse event was genitourinary symptoms. Conclusion: In this study, the effectiveness of dapagliflozin in improving glycemic control, blood pressure control, and weight loss was statistically significant. However, elderly and female patients, who have higher incidence of adverse events, should use dapagliflozin cautiously.

• Korean Journal of Clinical Pharmacy
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• v.27 no.2
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• pp.99-104
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• 2017

Objectives: This study aimed to compare effects on glycemic control and weight loss between the metformin/dapagliflozin combination and the metformin/sitagliptin combination in type 2 diabetic patients. Methods: This study retrospectively reviewed the medical records, from January $1^{st}$ 2015 to March $31^{st}$ 2016, of type 2 diabetic patients who were older than 18 and were prescribed with dapagliflozin or sitagliptin in combination with metformin. Hemoglobin $A_{1c}$ ($HbA_{1c}$) levels and weights were measured every 3 months. Results: The dapagliflozin group showed a greater decrease in $HbA_{1c}$ levels after 3 months (-0.75% vs. 0.01%, P<0.001), 6 months (-0.36% vs. 0.08%, P=0.029), and 9 months (-0.53% vs. 0.08%, P=0.046) compared to the sitagliptin group. Also, the dapagliflozin group showed a greater significant decrease in the rate of change in $HbA_{1c}$ levels after 3 months (-0.09 vs. 0.01, P<0.001), 6 months (-0.04 vs. 0.01, P=0.031), 9 months (-0.07 vs. 0.02, P=0.029), and 12 months (-0.05 vs. 0.05, P=0.047). Furthermore, the dapagliflozin group showed a greater decrease in amount of weight change after 3 months (-2.46 kg vs. 0.37 kg, P<0.001), 6 months (-3.02 kg vs. 0.13 kg, P<0.001), and 9 months (-2.27 kg vs. 0.50 kg, P=0.002). Finally, the dapagliflozin group showed a greater decrease in the rate of change in weight after 3 months (-3.10% vs. 0.52%, P<0.001), 6 months (-3.83% vs. 0.21%, P<0.001), 9 months (-2.84% vs. 0.79%, P=0.002), and 12 months (-4.91% vs. 0.44%, P<0.001). Conclusions: It was concluded that dapagliflozin is more effective than sitagliptin for type 2 diabetic patients.

• The Korean Journal of Physiology and Pharmacology
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• v.23 no.1
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• pp.55-62
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• 2019

HM41322 is a novel oral sodium-glucose cotransporter (SGLT) 1/2 dual inhibitor. In this study, the in vitro and in vivo pharmacokinetic and pharmacologic profiles of HM41322 were compared to those of dapagliflozin. HM41322 showed a 10-fold selectivity for SGLT2 over SGLT1. HM41322 showed an inhibitory effect on SGLT2 similar to dapagliflozin, but showed a more potent inhibitory effect on SGLT1 than dapagliflozin. The maximum plasma HM41322 level after single oral doses at 0.1, 1, and 3 mg/kg were 142, 439, and 1830 ng/ml, respectively, and the $T_{1/2}$ was 3.1 h. HM41322 was rapidly absorbed and reached the circulation within 15 min. HM41322 maximized urinary glucose excretion by inhibiting both SGLT1 and SGLT2 in the kidney. HM41322 3 mg/kg caused the maximum urinary glucose excretion in normoglycemic mice ($19.32{\pm}1.16mg/g$) at 24 h. In normal and diabetic mice, HM41322 significantly reduced glucose excursion. Four-week administration of HM41322 in db/db mice reduced HbA1c in a dose dependent manner. Taken together, HM41322 showed a favorable preclinical profile of postprandial glucose control through dual inhibitory activities against SGLT1 and SGLT2.

• Korean Journal of Clinical Pharmacy
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• v.28 no.3
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• pp.243-249
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• 2018

Background: The new type of diabetes treatment, SGLT2 inhibitors, has been approved for monotherapy and combination therapy, but medical insurance is only allowed in combination therapy with metformin, which is the first choice for type 2 diabetes treatment. Methods: The SGLT2 inhibitors prescribed in Korea are dapagliflozin, empagliflozin and ipragliflozin. A review was conducted using Pubmed to evaluate efficacy and safety for these medications with metformin combination therapy. 10 studies were selected by searching for keywords and related references and were reviewed in full. The mechanism of action, pharmacokinetics, and the economics of treatment with SGLT2 inhibitors were examined. Results: SGLT2 inhibitors had moderate glycemic control when added to the treatment of patients with type 2 diabetes who were not being regulated by metformin monotherapy. They also showed positive effects such as weight loss, as well as the lowering of blood pressure. Hypotension and serious side effects were relatively low. However, the risk of genital infection was increased. Conclusion: The SGLT2 inhibitors are a new class of drugs that promote glucose excretion in the urine. They are a good choice for combination therapy with metformin for the treatment of type 2 diabetes, with weight loss and very low risk of serious side effects.

• Journal of Medicine and Life Science
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• v.20 no.3
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• pp.126-130
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• 2023

Sodium-glucose cotransporter-2 (SGLT2) inhibitors have become increasingly prescribed because of their proven protective effects on the heart and kidneys, and carbohydrate-restricted diets are popular therapeutic approaches for patients with obesity and diabetes. A 28-year-old obese woman with recently diagnosed diabetes developed euglycemic diabetic ketoacidosis (DKA) while on dapagliflozin, an SGLT2 inhibitor, and following a carbohydrate-restricted diet. She presented with nausea, vomiting, and epigastric pain. Hospital tests showed a blood glucose of 172 mg/dL, metabolic acidosis, and increased ketone levels, confirming euglycemic DKA. Treatment involved discontinuing dapagliflozin and administering fluids, glucose, and insulin. She recovered and was discharged on the fourth day. This is considered a case of euglycemic DKA induced by SGLT2 inhibitors and triggered by a carbohydrate-restricted diet. This case highlights the importance of physicians in confirming the symptoms and laboratory results of DKA, even in patients with normal blood glucose levels taking SGLT2 inhibitors and following carbohydrate-restricted diets. It is also crucial to advise patients to maintain an adequate carbohydrate intake.

• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.2938-2940
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• 2011

Novel C-aryl glucoside SGLT2 inhibitors containing triazine motif were designed and synthesized for biological evaluation. Among the compounds assayed, triazine containing methoxy moiety 18 demonstrated the best in vitro inhibitory activity against hSGLT2 in this series to date ($IC_{50}$ = 24.9 nM).