The Relationship between Increases in Morning Spot Urinary Glucose Excretion and Decreases in HbA1C in Patients with Type 2 Diabetes After Taking an SGLT2 Inhibitor: A Retrospective, Longitudinal Study

Kim, So Ra; Lee, Yong-Ho; Kang, Eun Seok; Soo, Bong; Lee, Byung Wan

doi:10.1007/s13300-017-0248-5

Cited by 7 publications

(8 citation statements)

References 14 publications

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“…We also demonstrate that while urinary glucose excretion is a direct measure of SGLT inhibitor action, FGE did not improve prediction of ΔHbA1c in this study. This finding accords with that of a retrospective Korean study that found no association between urine glucose/creatinine ratio and ΔHbA1c 12 weeks after starting either dapagliflozin or ipragliflozin 18 . It is possible that changes in medication, diet and exercise during the study hampered our ability to identify a relationship between glycosuria and ΔHbA1c.…”

Section: Discussionsupporting

confidence: 89%

Factors that predict glycaemic response to sodium‐glucose linked transporter (SGLT) inhibitors

Harding

Bediaga

Galligan

et al. 2021

Internal Medicine Journal

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Aim To determine the clinical and biochemical variables associated with change in HbA1c in patients with type 2 diabetes who start sodium‐glucose linked transporter (SGLT) inhibitor therapy. Methods We performed a prospective cohort study (ACTRN12616000833460) of 48 adults (30 male, 18 female) with type 2 diabetes who attended a tertiary hospital diabetes clinic. Fasting serum and urine samples, collected during clinic visits prior to and at 1, 12 and 24 weeks after commencing SGLT inhibitor treatment, were analysed for HbA1c, electrolytes, urea, creatinine and glucose. Results After 12 weeks, SGLT inhibitor therapy was associated with respective median (97% CI) decreases in weight, blood pressure, HbA1c and urine albumin/creatinine ratio of 3.0 (1.7–3.4) kg, 8 (2–16)/4 (3–9) mmHg, 6 (3–14) mmol/mol and 0.69 (0.18–1.8) mg/mmol. These effects persisted to 24 weeks. Urinary frequency and genitourinary infection were common adverse effects. Baseline HbA1c and eGFR independently predicted ΔHbA1c at 12 weeks whereas only baseline HbA1c independently predicted ΔHbA1c at 24 weeks. Urinary fractional glucose excretion and change in fasting glucose 1 week after starting SGLT inhibitor did not contribute to prediction of glycaemic response. Conclusions SGLT inhibitor therapy in a hospital clinic setting was associated with clinical improvements comparable to those observed in clinical trials but with higher incidence of genitourinary side‐effects. Baseline HbA1c and eGFR, but not urine fractional glucose excretion, predicted glycaemic response.

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Section: Discussionsupporting

confidence: 89%

Factors that predict glycaemic response to sodium‐glucose linked transporter (SGLT) inhibitors

Harding

Bediaga

Galligan

et al. 2021

Internal Medicine Journal

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“…We initially used ΔUGE as a PD biomarker because of its mechanism of action and we found that the maximum effect and affinity on UGE was significantly different between different SGLT2 inhibitors and between patients and healthy subjects. It was consistent with one paper which even concluded that the ΔUGE has no relationship with FPG or HbA1c, which impeded the achievement of our preset aims 27 . Therefore, we proposed a better mechanistic PD biomarker to construct this system‐dependent model.…”

Section: Discussionsupporting

confidence: 85%

A model‐based meta analysis study of sodium glucose co‐transporter‐2 inhibitors

Yao

Zhou

Lee

et al. 2023

CPT Pharmacom & Syst Pharma

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Type 2 diabetes mellitus (T2DM) agent sodium-glucose co-transporter 2 (SGLT2) inhibitors show special benefits in reducing body weight and heart failure risks.To accelerate clinical development for novel SGLT2 inhibitors, a quantitative relationship among pharmacokinetics, pharmacodynamics, and disease end points (PK/PD/end points) in healthy subjects and patients with T2DM was developed. PK/PD/end point data in published clinical studies for three globally marketed SGLT2 inhibitors (dapagliflozin, canagliflozin, and empagliflozin) were collected according to pre-set criteria. Overall, 80 papers with 880 PK, 27 PD, 848 fasting plasma glucose (FPG), and 1219 hemoglobin A1c (HbA1c) data were collected.A two-compartmental model with Hill's equation was utilized to capture PK/ PD profiles. A novel translational biomarker, the change of urine glucose excretion (UGE) from baseline normalized by FPG (ΔUGE c ) was identified to bridge healthy subjects and patients with T2DM with different disease statuses. ΔUGE c was found to have a similar maximum increase with different half-maximal effective concentration values of 56.6, 2310, and 841 mg/mL•h for dapagliflozin, canagliflozin, and empagliflozin respectively. ΔUGE c will change FPG based on linear function. HbA1c profiles were captured by indirect response model. Additional placebo effect was also considered for both end points. The PK/ΔUGE c /FPG/ HbA1c relationship was validated internally using diagnostic plots and visual assessment and further validated externally using the fourth globally approved same-in-class drug (ertugliflozin). This validated quantitative PK/PD/end point relationship offers novel insight into long-term efficacy prediction for SGLT2 inhibitors. The novelty identified ΔUGE c could make the comparison of different SGLT2 inhibitors' efficacy characteristics easier, and achieve early prediction from healthy subjects to patients.

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“…In a Japanese clinical trial, the young age group (≤ 40 years) showed a better effectiveness in glycemic control with a larger increase in urine glucose excretion [ 16 ]. However, another study reported that a larger urinary glucose excretion did not reflect a better HbA1c reduction [ 18 ]. As expected, these results suggest that the insulin-independent mechanism for the glucose-lowering effect of an SGLT2 inhibitor is not simple.…”

Section: Discussionmentioning

confidence: 99%

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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The Relationship between Increases in Morning Spot Urinary Glucose Excretion and Decreases in HbA1C in Patients with Type 2 Diabetes After Taking an SGLT2 Inhibitor: A Retrospective, Longitudinal Study

Cited by 7 publications

References 14 publications

Factors that predict glycaemic response to sodium‐glucose linked transporter (SGLT) inhibitors

Factors that predict glycaemic response to sodium‐glucose linked transporter (SGLT) inhibitors

A model‐based meta analysis study of sodium glucose co‐transporter‐2 inhibitors

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

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