Link between body weight changes and metabolic parameters in drugs naïve subjects with type 2 diabetes treated with canagliflozin monotherapy

Kutoh, Eiji; Wada, Asuka; Kuto, Alexandra N.; Hayashi, Jyunka; Kurihara, Rumi

doi:10.1080/21548331.2020.1732098

Cited by 3 publications

(6 citation statements)

References 26 publications

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“…Antiglutamic acid decarboxylase (GAD) antibody was measured in some patients to exclude those with T1DM (Mitsubishi LSI or BML, Tokyo, Japan). HOMA-R, HOMA-B, QUICKI, CPR-index or adipo-IR were calculated as previously described [18,20,21]. HOMA-R = insulin x FBG/405, HOMA-B = insulin x 360/(FBG-63), QUICKI = 1/[log(insulin) + log(FBG)], CPR-index = c-peptide/FBG x100 and adipo-IR = insulin x FFA.…”

Section: Laboratory Measurementsmentioning

confidence: 99%

“…The protocol of this project is basically described previously [18]. The subjects were recruited from the outpatient's divisions of the affiliated hospitals of the first author (EK).…”

Section: Subjectsmentioning

confidence: 99%

“…As a matter of fact, we previously reported that certain populations treated with SGLT-2 inhibitors including ipragliflozin and canagliflozin do no lose weight or even have increased weight. Nevertheless no differences in glycemic efficacies were observed irrespective of weight changes with these drugs [17,18]. Surprisingly, those who had weight gain with canagliflozin were shown to have similar glucose lowering and/or insulin sensitizing properties in comparison to others who had efficient weight loss [18].…”

Section: Introductionmentioning

confidence: 97%

“…Nevertheless no differences in glycemic efficacies were observed irrespective of weight changes with these drugs [17,18]. Surprisingly, those who had weight gain with canagliflozin were shown to have similar glucose lowering and/or insulin sensitizing properties in comparison to others who had efficient weight loss [18]. As reviewed by other researchers, the link between the degrees of weight loss and reductions of blood glucose levels with SGLT2-inhibitors are still unclear [19].…”

Section: Introductionmentioning

confidence: 99%

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Regulation of Adipose Tissue Insulin Resistance and Diabetic Parameters in Drug Naïve Subjects with Type 2 Diabetes Treated with Canagliflozin Monotherapy

Kutoh

Kuto²,

Ozawa

et al. 2023

Drug Res (Stuttg)

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The objective of this study is to investigate the link between the baseline/changes of body weight and those of diabetic parameters during treatment with an SGLT-2 inhibitor. Drug naïve subjects with T2DM received canagliflozin monotherapy for 3 months. Adipo-IR was selected as the significant factor responsible for the changes of (Δ)BMI with this drug. While no correlations were noted between ΔBMI and ΔFBG, ΔHbA1c, ΔHOMA-R or ΔQUICKI, significant negative correlations were observed between ΔBMI and Δadipo-IR (R=−0.308). The subjects were divided into two groups with baseline BMI<25 (n=31, group alpha) or≥25 (n=39, group beta). Baseline levels of FBG, HbA1c, T-C, TG, non-HDL-C, LDL-C showed no differences between group alpha and beta. The subjects were also divided into two equal numbers of subjects (n=35 each) based on the changes of weight: the lower half (−3.6%, p<0.00001, group A) and the upper half (0.1%, n.s., group B) of ∆BMI. FBG, HbA1c or HOMA-R significantly, similarly decreased, while QUICKI increased in group A and B. TG significantly decreased, while HDL-C increased in group A. HOMA-B significantly increased, while adipo-IR insignificantly decreased in group B. Collectively, these results suggest that 1) adipose tissue insulin resistance is responsible for the weight changes with canagliflozin. 2) baseline levels of glycemic and some lipid parameters were similar between obese and non-obese populations. 3) weight changes with canagliflozin were not associated with its glycemic or insulin sensitizing efficacies but were linked to adipose-tissue insulin resistance, some lipids, and beta-cell function.

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Section: Laboratory Measurementsmentioning

confidence: 99%

“…The protocol of this project is basically described previously [18]. The subjects were recruited from the outpatient's divisions of the affiliated hospitals of the first author (EK).…”

Section: Subjectsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of Adipose Tissue Insulin Resistance and Diabetic Parameters in Drug Naïve Subjects with Type 2 Diabetes Treated with Canagliflozin Monotherapy

Kutoh

Kuto²,

Ozawa

et al. 2023

Drug Res (Stuttg)

Self Cite

View full text Add to dashboard Cite

show abstract

“…Recent clinical trials have demonstrated the effect of SGLT2i in improving insulin sensitivity. Kutoh et al found that SGLT2i administration in patients with T2DM lowered body mass index and HOMA-R [ 88 ]. SGLT2i and other DM medications, such as the GLP-1 agonist, were also used in patients with hereditary disease, such as Prader–Willi syndrome [ 89 ].…”

Section: Metabolic Factors Influenced By Sglt2imentioning

confidence: 99%

Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

Hou

Zheng

Yen

et al. 2020

IJMS

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The development of sodium-glucose transporter 2 inhibitor (SGLT2i) broadens the therapeutic strategies in treating diabetes mellitus. By inhibiting sodium and glucose reabsorption from the proximal tubules, the improvement in insulin resistance and natriuresis improved the cardiovascular mortality in diabetes mellitus (DM) patients. It has been known that SGLT2i also provided renoprotection by lowering the intraglomerular hypertension by modulating the pre- and post- glomerular vascular tone. The application of SGLT2i also provided metabolic and hemodynamic benefits in molecular aspects. The recent DAPA-CKD trial and EMPEROR-Reduced trial provided clinical evidence of renal and cardiac protection, even in non-DM patients. Therefore, the aim of the review is to clarify the hemodynamic and metabolic modulation of SGLT2i from the molecular mechanism.

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Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience

et al. 2022

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We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive patients were retrospectively analyzed. Only those with a full assessment at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment with SGLT2i or GLP1RA were included in the study (n = 167). At baseline, patients had a high mean body weight (BW), abdominal circumference (AC), body mass index (BMI), and HOMA index. Despite normal C-peptide values, 39 patients were being treated with insulin (up to 120 IU/day). During therapy, a progressive improvement in BW, BMI, and AC was observed with both the molecules. Fasting glucose and glycated Hb decrease was already significant at T3 in all patients, while the HOMA index selectively improved with SGLT2i therapy. Renal function parameters remained stable regardless of the drug used. Finally, SGLT2i reduced serum uric acid and improved the lipid profile, while GLP1RA reduced serum levels of liver enzymes. Both the therapeutic regimens allowed a significant reduction or complete suspension of unnecessary insulin therapies. Our real life data confirm the results obtained from randomized clinical trials and should be taken as a warning against inappropriate use of insulin in patients with preserved β-cell function.

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Link between body weight changes and metabolic parameters in drugs naïve subjects with type 2 diabetes treated with canagliflozin monotherapy

Cited by 3 publications

References 26 publications

Regulation of Adipose Tissue Insulin Resistance and Diabetic Parameters in Drug Naïve Subjects with Type 2 Diabetes Treated with Canagliflozin Monotherapy

Regulation of Adipose Tissue Insulin Resistance and Diabetic Parameters in Drug Naïve Subjects with Type 2 Diabetes Treated with Canagliflozin Monotherapy

Molecular Mechanisms of SGLT2 Inhibitor on Cardiorenal Protection

Effectiveness and clinical benefits of new anti-diabetic drugs: A real life experience

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