Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI

IntroductionInhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI.MethodsPET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls.ResultsMTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; p<0.001). The higher the GRP value in kidneys of T2DMSGLT2i, the lower was the glycated hemoglobin level 3 months after therapy initiation.ConclusionMTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2 weeks after therapy with SGLT2i begins. GRP in T2DMSGLT2i was associated with better long-term glycemic response 3 months after initiation of therapy.Trial registration numberNCT03557138.

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Safety and effectiveness of ipragliflozin in Japanese patients with type 2 diabetes mellitus and impaired renal function: subgroup analysis of a 3-year post-marketing surveillance study (STELLA-LONG TERM)

Diabetology International ◽

10.1007/s13340-020-00470-6 ◽

2020 ◽

Author(s):

Kazuyuki Tobe ◽

Hiroshi Maegawa ◽

Ichiro Nakamura ◽

Satoshi Uno

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Function ◽

Impaired Renal Function ◽

Japanese Patients ◽

Post Marketing Surveillance ◽

Post Marketing

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Long-term evolution of renal function in patients with type 2 diabetes mellitus: a registry-based retrospective cohort study

BMJ Open ◽

10.1136/bmjopen-2013-004029 ◽

2013 ◽

Vol 3 (12) ◽

pp. e004029 ◽

Cited By ~ 14

Author(s):

Geert Goderis ◽

Gijs Van Pottelbergh ◽

Carla Truyers ◽

Viviane Van Casteren ◽

Etienne De Clercq ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Function ◽

Cohort Study ◽

Retrospective Cohort Study ◽

Retrospective Cohort ◽

Term Evolution

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The Value of Ketone Bodies in the Evaluation of Kidney Function in Patients with Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2021/5596125 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Yimei Li ◽

Yongze Zhang ◽

Ximei Shen ◽

Fengying Zhao ◽

Sunjie Yan

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Function ◽

Kidney Function ◽

Ketone Bodies ◽

Normal Group ◽

Renal Tubules ◽

Circulating Levels

Objectives. Recent studies have shown that the slightly elevated circulating levels of ketone bodies (KBs) played a significant role in the treatment of various diseases. This study is aimed at investigating the association between different levels of KBs and kidney function in patients with type 2 diabetes mellitus (T2DM). Methods. A retrospective study of 955 patients with T2DM (426 women and 529 men) admitted to our hospital from December 2017 to September 2019 was conducted. Patients were divided into different groups in line with the levels of KBs (low-normal group: 0.02-0.04 mmol/L, middle-normal group: 0.05-0.08 mmol/L, high-normal group: 0.09-0.27 mmol/L, and slightly elevated group: >0.27 and <3.0 mmol/L). Results. In the present study, individuals with high-normal levels of KBs had the lowest risk of diabetic kidney disease (DKD) and increased peak systolic velocity (PSV); those with middle-normal levels of KBs had the lowest risk of increased renal arterial resistive index (RI), with a positive correlation between increased α1-microglobulin and KB concentration. In addition, the indicators of glomerulus, renal tubules, and renal arteries were all poor with slightly elevated circulating levels of KBs, and KB concentration lower than 0.09 mmol/L can be applied as the threshold for low risk of renal function damage. Conclusions. In summary, slightly elevated circulating levels of ketone bodies are not of benefit for renal function in patients with type 2 diabetes mellitus.

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PO426 EFFICACY AND SAFETY OF LUSEOGLIFLOZIN IN VARIOUS LEVELS OF RENAL FUNCTION IN JAPANESE PATIENTS WITH TYPE 2 DIABETES MELLITUS: ANALYSIS OF POOLED DATA FROM LONG-TERM PHASE 3 TRIALS

Diabetes Research and Clinical Practice ◽

10.1016/s0168-8227(14)70720-x ◽

2014 ◽

Vol 106 ◽

pp. S263-S264

Author(s):

M. Ubukata ◽

Y. Samukawa ◽

S. Sakai ◽

T. Sasaki ◽

M. Haneda ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Function ◽

Japanese Patients ◽

Efficacy And Safety ◽

Phase 3 ◽

Pooled Data

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Long-Term Effectiveness and Safety of SGLT-2 Inhibitors in an Italian Cohort of Patients with Type 2 Diabetes Mellitus

Journal of Diabetes Research ◽

10.1155/2019/3971060 ◽

2019 ◽

Vol 2019 ◽

pp. 1-8 ◽

Cited By ~ 8

Author(s):

Maria Mirabelli ◽

Eusebio Chiefari ◽

Patrizia Caroleo ◽

Raffaella Vero ◽

Francesco Saverio Brunetti ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Renal Function ◽

Hypoglycemic Agents ◽

Rapid Decline ◽

Diabetic Patients ◽

Tract Infections

Background. SGLT-2 (sodium-glucose cotransporter-2) inhibitors are a novel class of oral hypoglycemic agents for the management of type 2 diabetes mellitus (T2DM). Herein, we aimed to assess the long-term effectiveness and safety of SGLT-2 inhibitors in a Southern Italy population of subjects affected by T2DM. Patients and Methods. 408 diabetic patients treated with one of the three SGLT-2 inhibitors currently available in Italy (dapagliflozin, empagliflozin, and canagliflozin), either alone or in combination with other antidiabetic drugs, were retrospectively assessed at baseline, during, and after 18 months of continuous therapy. Results. Treatment with SGLT-2 inhibitors resulted in a median decrease in HbA1c of 0.9%, with a percentage of decrement of 12 in relation to the baseline value, followed by a significant reduction (P<0.001) in fasting plasma glucose. Variations in HbA1c occurred independently of the baseline clinical or biochemical characteristics. In addition, treatment with SGLT-2 inhibitors reduced body weight (P<0.008) and decreased diastolic blood pressure (P=0.004). With regard to safety outcomes, 66 patients out of 91 stopped SGLT-2 inhibitors during follow-up because of chronic or recurring genital infections, while the rest experienced other adverse events, such as urinary tract infections, polyuria, nausea, hypotension, dizziness, acute coronary event, worsening of glycemic control status, and rapid deterioration of renal function. Conclusion. In our patients’ population, the glycometabolic effects of SGLT-2 inhibitors were durable and comparable to those observed in multicenter randomized controlled trials. This notwithstanding safety concerns must be raised regarding the frequent occurrence of genitourinary infections and the risk of a rapid decline of renal function in patients with evidence of volume depletion and/or receiving other medications which can adversely affect kidney function.

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