Clinical parameters affecting dapagliflozin response in patients with type 2 diabetes

Lee, Jun-Yeop; Kim, Gi Hong; Kim, S.R.; Lee, Young-Ho; Lee, B.-W.; Soo, Bong; Kang, Eun Seok

doi:10.1016/j.diabet.2016.11.005

Cited by 9 publications

(17 citation statements)

References 12 publications

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“…Similar to previous studies [ 14 , 15 , 17 ], a significant association between body weight change and glucose reduction was not observed in our study. Because SGLT2 inhibitors impede glucose reabsorption from the proximal renal tubules, dapagliflozin induces a complimentary increase in urinary glucose excretion [ 17 ].…”

Section: Discussionsupporting

confidence: 89%

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Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea

et al. 2018

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IntroductionSodium glucose co-transporter 2 (SGLT2) inhibitors, such as dapagliflozin, have demonstrated favorable effects in patients with type 2 diabetes (T2D). However, there are limited reports in the literature regarding the glucose-lowering effects of SGLT2 inhibitors in actual clinical settings.MethodsThe post-marketing surveillance data from a longitudinal prospective study of 2007 patients with T2D who were prescribed dapagliflozin (10 mg/day) were analyzed (ClinicalTrials.gov, NCT02252224).ResultsAfter 12 weeks of dapagliflozin treatment, glycated hemoglobin (HbA1c) and body mass index were significantly decreased (P < 0.001) from 8.1 ± 1.3% to 7.5 ± 1.2% and from 28.1 ± 4.4 to 27.6 ± 4.2 kg/m2, respectively. Both body weight and HbA1c were reduced in 67.7% of patients, and HbA1c was lowered in 75.1%. Younger age, male sex, shorter diabetes duration, higher baseline HbA1c and estimated glomerular filtration rate (eGFR), and having dapagliflozin as add-on therapy were associated with stronger HbA1c reductions after dapagliflozin use (all P < 0.05). Moreover, subgroup analysis of eGFR of subjects with renal hyperfiltration (eGFR ≥ 120 ml/min/1.73 m2) showed the largest reduction in glucose level (% change, − 9.5; 95% CI − 6.8 to − 12.3 for HbA1c; P < 0.001). Multivariable logistic regression analysis showed that recent T2D diagnosis and higher HbA1c at baseline in patients who received an add-on regimen of dapagliflozin were statistically significantly associated with a dapagliflozin response (all P < 0.05).ConclusionsDapagliflozin provides benefits for glycemic control and body weight. Patients in a relatively early stage of the course of diabetes with renal hyperfiltration might be more suitable for and gain maximal benefit from dapagliflozin treatment.Trial RegistrationClinicalTrials.gov identifier, NCT02252224.FundingAstraZeneca.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0470-9) contains supplementary material, which is available to authorized users.

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Section: Discussionsupporting

confidence: 89%

“…These characteristics have been noted in previous studies. A retrospective report showed that only higher baseline HbA1c and preserved eGFR (> 90 ml/min/1.73 m 2 ) had positive correlations with glucose-lowering effectiveness [ 14 ]. Moreover, in a pooled analysis report, the HbA1c-lowering effect was decreased as eGFR declined [ 15 ].…”

Section: Discussionmentioning

confidence: 99%

Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea

et al. 2018

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“…Considering these results, an SGLT2i was frequently added to the regimens of obese patients in our study. Additionally, it has been reported that the efficacy of SGLT2is is greater in patients with preserved renal function than in those without preserved renal function [22,23]. In our study, the SGLT2i add-on group demonstrated higher eGFR than the other two groups.…”

Section: Discussionsupporting

confidence: 55%

Clinical Efficacy of Quadruple Oral Therapy for Type 2 Diabetes in Real-World Practice: A Retrospective Observational Study

et al. 2020

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Introduction: We aimed to evaluate the effectiveness of quadruple oral therapy in patients with inadequately controlled type 2 diabetes (T2D) with the use of three types of oral hypoglycemic agents. Methods: Medical records of 318 patients with T2D who were prescribed quadruple therapy in the Asan Medical Center were reviewed. Changes in glycated hemoglobin (HbA1c) and fasting plasma glucose (FPG) levels from baseline were assessed. The regimens of quadruple oral therapy included the following: (1) thiazolidinedione (TZD) add-on to metformin (MET) ? sulfonylurea (SU) ? dipeptidyl peptidase 4 inhibitor (DPP4i), (2) sodium-glucose cotransporter 2 inhibitor (SGLT2i) add-on to MET ? SU ? DPP4i, and (3) DPP4i add-on to MET ? SU ? TZD. Results: The TZD add-on significantly reduced HbA1c levels by 1.1% (from 9.0 ± 1.1 to 7.9 ± 1.1%, P \ 0.001) and FPG levels by 41.4 mg/dL (from 188.9 ± 45.9 to 147.4 ± 51.3 mg/dL, P \ 0.001). The SGLT2i add-on changed the mean HbA1c level from 8.9 ± 1.0 to 7.8 ± 1.0%, a reduction of 1.1% (P \ 0.001) and changed the mean FPG level from 193.4 ± 46.2 to 152.6 ± 37.0 mg/dL, a reduction of 40.8 mg/ dL (P \ 0.001). Finally, the DPP4i add-on reduced HbA1c levels by 1.3% (from 9.1 ± 1.3 to 7.8 ± 1.4%, P \ 0.001) and FPG levels by 39.3 mg/dL (from 190.7 ± 45.3 to 151.4 ± 41.6 mg/dL, P \ 0.001). Patients with higher baseline HbA1c levels (C 9.0%) showed a better response to quadruple therapy than those with baseline HbA1c levels lower than 9.0% for all three regimens. Conclusion: Quadruple oral hypoglycemic therapy can be a feasible option in patients with T2D.

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“…In previous studies that evaluated the clinical characteristics of glycaemic response to SGLT2is, baseline BMI was not associated with the glucose-lowering effect of SGLT2i treatment 90,91 . In the three cardiovascular outcome trials (EMPA-REG OUTCOME, CANVAS and DECLARE-TIMI 58), no statistically significant interaction was observed regarding the primary cardiovascular composite end point when comparing patients with BMI <30 kg/m² versus ≥30 kg/m 2 (refs 39,92,93 ), a finding also confirmed in the renal outcome trial CREDENCE 94 and in DAPA-HF 95 .…”

Section: Sglt2is In Different Populations Obesitymentioning

confidence: 81%

Sodium–glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus

2020

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The management of type 2 diabetes mellitus (T2DM) is becoming increasingly complex. Sodium-glucose cotransporter type 2 inhibitors (SGLT2is) are the newest antidiabetic agents for T2DM. By targeting the kidney, they have a unique mechanism of action, which results in enhanced glucosuria, osmotic diuresis and natriuresis, thereby improving glucose control with a limited risk of hypoglycaemia and exerting additional positive effects such as weight loss and the lowering of blood pressure. Several outcome studies with canagliflozin, dapagliflozin or empagliflozin reported a statistically significant reduction in major cardiovascular events, hospitalization for heart failure and progression to advanced renal disease in patients with T2DM who have established atherosclerotic cardiovascular disease, several cardiovascular risk factors, albuminuric mild to moderate chronic kidney disease or heart failure. Current guidelines proposed a new paradigm in the management of T2DM, with a preferential place for SGLT2is, after metformin, in patients with atherosclerotic cardiovascular disease, heart failure and progressive kidney disease. Ongoing trials might extend the therapeutic potential of SGLT2is in patients with, but also without, T2DM. This Review provides an update of the current knowledge on SGLT2is, moving from their use as glucose-lowering medications to their new positioning as cardiovascular and renal protective agents.

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Clinical parameters affecting dapagliflozin response in patients with type 2 diabetes

Cited by 9 publications

References 12 publications

Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea

Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea

Clinical Efficacy of Quadruple Oral Therapy for Type 2 Diabetes in Real-World Practice: A Retrospective Observational Study

Sodium–glucose cotransporter type 2 inhibitors for the treatment of type 2 diabetes mellitus

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