Regulation of serum uric acid with canagliflozin monotherapy in type 2 diabetes: A potential link between uric acid and pancreatic β-cell function

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

doi:10.5414/cp203513

Cited by 9 publications

(12 citation statements)

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“…Furthermore significant negative correlations were seen between the A1c index and the change of (∆) UA in this group. This may support our previous hypothesis that elevated serum UA may enhance beta-cell functions, thereby resulting in better glycemic efficacy [14].…”

Section: Glycemic Efficacies and Safety Of Sitagliptinsupporting

confidence: 90%

“…DPP-4 inhibitors including sitagliptin increases the active forms of GLP-1 and glucose-dependent insulinotropic polypeptide (GIP). These peptide hormones are known to enhance firstphase insulin secretion through cAMP and subsequent activation of Epac2A/Rap1 pathway in the pancreas [14][15][16]. Thus, those with high postprandial glucose levels may benefit from DPP-4 inhibitor therapy.…”

Section: Glycemic Efficacies and Safety Of Sitagliptinmentioning

confidence: 99%

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Sitagliptin as an Initial Therapy and Differential Regulations of Metabolic Parameters Depending on its Glycemic Response in Subjects with Type 2 Diabetes

Kutoh¹,

Kuto²,

Wada³

et al. 2020

Drug Res (Stuttg)

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The aim of this study is to investigate whether sitagliptin can be used as an initial drug for T2DM and to evaluate its effects on metabolic parameters in relation to its glycemic efficacies. The subjects received 25−50 mg/day sitagliptin monotherapy (n=69). At 3 months, they were divided into three groups (n=23 each) according to the novel parameter called “A1c index” which is designed to assess glycemic efficacy. The metabolic parameters were compared between good-responders and poor-responders. These two groups acted as a control each other. In the overall subjects, efficient reductions of HbA1c (10.16–8.22%) were observed with few adverse events. Significant correlations were seen between the A1c index and changes of (∆)nonHDL-C (R=0.250) or ∆LDL-C (R=0.368). At baseline, T-C, nonHDL-C and BMI levels were significantly lower in good-responders than poor-responders. At 3 months, in good-responders, HbA1c levels effectively decreased (11.03–7.00%). Indexes for insulin sensitivity/resistance [HOMA-R and 20/(C-peptide x FBG)] and beta-cell function (HOMA-B and CPR-index) ameliorated. T-C, nonHDL-C and LDL-C significantly decreased, while BMI increased. However, in poor-responders, no changes in these parameters were noted. Collectively, these results suggest that 1) Sitagliptin can be used as a first-line drug for T2DM and its glycemic efficacy is linked to some atherogenic lipids. 2) Those with lower T-C, nonHDL-C and BMI appear to respond better with this drug. 3) Good glycemic efficacy of sitagliptin is medicated through reduced insulin resistance as well as enhanced beta-cell functions. Body weight increased, while some atherogenic cholesterol decreased in good-responders.

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Section: Glycemic Efficacies and Safety Of Sitagliptinsupporting

confidence: 90%

Section: Glycemic Efficacies and Safety Of Sitagliptinmentioning

confidence: 99%

Sitagliptin as an Initial Therapy and Differential Regulations of Metabolic Parameters Depending on its Glycemic Response in Subjects with Type 2 Diabetes

Kutoh¹,

Kuto²,

Wada³

et al. 2020

Drug Res (Stuttg)

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“…Currently, the relationship between SUA and insulin resistance and beta-cell function has been established in several studies in patients with diabetes. [15][16][17][18] However, a large-scale study investigating this relationship in nondiabetic population is still lacking. In the present study, we explored the association of SUA with glucose homeostasis in nondiabetic individuals as assessed by HOMA models, which may help to define the role of SUA in the early natural history of type 2 diabetes.…”

Section: Introductionmentioning

confidence: 99%

The Association of Serum Uric Acid with Beta-Cell Function and Insulin Resistance in Nondiabetic Individuals: A Cross-Sectional Study

Huang

Wang

et al. 2021

DMSO

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Purpose Higher serum levels of uric acid (SUA) are associated with an increased risk of developing type 2 diabetes. Meanwhile, insulin resistance and beta-cell dysfunction are critical factors that mediate the progression from normal glucose tolerance to impaired fasting glucose (IFG) and type 2 diabetes. We aimed to investigate the association between SUA levels and insulin resistance and beta-cell dysfunction in individuals without diabetes, thus explicating the role of uric acid in the early stage of the natural history of type 2 diabetes. Patients and Methods We used cross-sectional data from the China Health and Nutrition Survey to examine the association. Insulin resistance and beta-cell dysfunction were estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index and homeostasis model assessment of beta-cell function (HOMA-beta) index, respectively. The associations were analyzed by using partial correlation analysis and multivariate logistic regressionl analysis. Results SUA levels were positively associated with fasting glucose, fasting insulin, HOMA-IR in the total population. After adjustment for age, drinking, smoking, living area, daily dietary nutrient intake, body mass index (BMI), estimated glomerular filtration rate (eGFR), hypertension, and dyslipidemia, compared with participants in the lowest quartile of SUA, the adjusted odds ratios for the fourth quartiles were 1.56(1.09-2.24) for IFG, 1.51(1.27-1.78) for insulin resistance, and 1.06(0.88-1.27) for beta-cell dysfunction. In the subgroup analysis, no interactions were found between serum uric acid and age, drinking status, smoking status, BMI, hypertension, or dyslipidemia (all p for interaction>0.05). Conclusion In nondiabetic individuals, SUA levels are independently associated with IFG and insulin resistance, while no significant association exists between SUA and beta-cell dysfunction.

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“…UA/Cr ratio: Serum uric acid-to creatinine ratio, eGFR: Estimated glomerular filtration rate calculated using CKD-EPI formula, WHtR: waist-to height ratio a link between pancreatic beta-cell function and antihyperglycemic efficacy [24]. Other studies report that canagliflozin had dual effects on the serum levels of uric acid and this effect depended on the baseline serum uric acid level [25]. Canagliflozin improves the serum uric acid if the baseline value is low and vice versa [25,26].…”

Section: Discussionmentioning

confidence: 99%

“…Other studies report that canagliflozin had dual effects on the serum levels of uric acid and this effect depended on the baseline serum uric acid level [25]. Canagliflozin improves the serum uric acid if the baseline value is low and vice versa [25,26]. Therefore, the effect of antidiabetic agents on the serum uric acid is variable, despite the fact that there is a link between serum uric acid level and the function of the pancreatic beta-cell.…”

Section: Discussionmentioning

confidence: 99%

Harmful versus beneficial effects of using short-term combined oral antidiabetic therapy: ‎An open label comparative clinical trial ‎

Baito

Alhassani

Al-Nimer

2021

Clinical Diabetology

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Background. Although oral antidiabetic drugs have many beneficial pleiotropic effects, they are not free from adverse reactions which may interfere with glucose homeostasis. This study aimed to assess the effects of oral antidiabetic drugs as add-on-therapy to metformin, on the metabolic, cardiac and renal determinants. Material and methods. A total number of seventy-eight type 2 diabetes (T2D) patients who were treated with metformin were allocated to add-on-therapy for 12 weeks, with glimepiride (4 mg/day, n = 26), sitagliptin (100 mg/day, n = 28), and canagliflozin (300 mg/day, n = 24). Anthropometric measurements, glycemic indices, and lipid and renal markers, were determined before and after the treatment. Results. All of the three treatments significantly decreased the glycemic indices, triglyceride-to-glucose index, and non-significantly altered the serum uric acidto creatinine ratio. Glimepiride significantly increased the waist-to-height ratio (0.630 ± 0.057 vs. 0.640 ± 0.057, P = 0.040), while sitaglipitin and canagliflozin significantly decreased it (0.650 ± 0.058 versus 0.640 ± 0.054, p = 0.009, and 0.650 ± 0.041 versus 0.630 ± 0.044, P < 0.001). Estimated glomerular filtration rate calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (mL/min/1.73 m 2 ) sig-nificantly declined in patients using glimepiride (109.0 ± 10.4 vs. 103.6 ± 10.9, P = 0.001), and sitagliptin (106.1 ± 12.4 vs. 103.3 ± 15.0, P = 0.013). Conclusion. Careful selection oral antidiabetic agents can protect T2D patients from harmful events, particularly those related to cardiovascular events and renal function. (Clin Diabetol 2021; 10

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Regulation of serum uric acid with canagliflozin monotherapy in type 2 diabetes: A potential link between uric acid and pancreatic β-cell function

Cited by 9 publications

References 0 publications

Sitagliptin as an Initial Therapy and Differential Regulations of Metabolic Parameters Depending on its Glycemic Response in Subjects with Type 2 Diabetes

Sitagliptin as an Initial Therapy and Differential Regulations of Metabolic Parameters Depending on its Glycemic Response in Subjects with Type 2 Diabetes

The Association of Serum Uric Acid with Beta-Cell Function and Insulin Resistance in Nondiabetic Individuals: A Cross-Sectional Study

Harmful versus beneficial effects of using short-term combined oral antidiabetic therapy: ‎An open label comparative clinical trial ‎

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