A 52‐week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The <scp>N‐ISM</scp> study

Kitazawa, Masaru; Kubo, Takashi; Suzuki, Hiromi; Matsunaga, Satoshi; Yamada, Mayuko H.; Ikarashi, Taro; Yamamoto, Masahiko; Furukawa, Kazuo; Iwanaga, Midori; Hatta, Mariko; Fujihara, Kazuya; Yamada, Takaho; Tanaka, Shiro; Sone, Hirohito

doi:10.1111/dom.14288

Cited by 17 publications

(12 citation statements)

References 35 publications

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“…The participants in these trials were aged between 18 to 70 years old. Among all included studies, ten trials reported changes in BMI and weight [28,29,[35][36][37][38][39][40][41][42], two studies only reported BMI [43,44], and six studies only reported body weight [45][46][47][48][49][50].…”

Section: Resultsmentioning

confidence: 99%

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

et al. 2021

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Background Sitagliptin is known as an antidiabetic agent inhibiting the dipeptidyl peptidase-4. Although sitagliptin may influence weight, controversial results have been reported, and there is no general agreement on this issue. Therefore, this study assessed the effect of sitagliptin as monotherapy and add-on therapy to metformin on weight reduction in overweight or obese cases with type 2 diabetes. Methods We reviewed the following databases to identify all relevant papers published until 1st April 2021: Web of Science, MEDLINE, Embase, Scopus, Cochrane Central Register of Controlled Trials Cochrane Library, and Google Scholar. The research included all clinical trials investigating the effect of sitagliptin in obese or overweight adult patients with type 2 diabetes without any language restriction. Results In total, eighteen randomized controlled trials with 2009 participants were included in our meta-analysis. Results showed supplementation of sitagliptin has led to weight loss for sitagliptin treated (MD −0.99; 95% CI; (−1.87, −0.12); p=0.026)) and sitagliptin+metformin treated groups (MD −1.09; 95% CI; (−1.69, −0.49); p<0.001)). Also, the intervention has influenced body mass index in sitagliptin treated (MD −0.23; 95% CI; (−0.45, 0.02); p=0.033)) and sitagliptin+metformin treated groups (MD −0.52; 95% CI; (−0.96, 0.08); p=0.020)) comparing to placebo. Conclusion Our results demonstrated that sitagliptin administration with or without metformin might reduce the body weight and body mass index if these drugs are taken for more than 6 months.

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Section: Resultsmentioning

confidence: 99%

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

et al. 2021

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“…Drug therapy and dietary interventions are effective ways to treat diabetes. Metformin, sulfonylureas, insulin, and other drugs can significantly relieve T2DM with a hypoglycemic effect, but they cannot prevent islet cell failure (Kitazawa et al, 2021;Taylor et al, 2021). Research on the dietary intervention of diabetes has been increasing rapidly, with multiple natural and nutritional products thought to benefit the treatment of diabetes.…”

Section: Discussionmentioning

confidence: 99%

Vitamin B3 inhibits apoptosis and promotes autophagy of islet β cells under high glucose stress

Yu¹,

Zhou²,

ZHANG³

et al. 2023

Biocell

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Background: Hyperglycemia is a typical symptom of diabetes. High glucose induces apoptosis of islet β cells. While autophagy functions in cytoprotection and autophagic cell death. The interaction between autophagy and apoptosis is important in the modulation of the function of islet β cells. Vitamin B3 can induce autophagy and inhibit islet β apoptosis. Method: The mechanism of vitamin B3-mediated protective effect on the function of islet β cells was explored by the method of western blot, immunofluorescence and flow cytometry. Results: In the present study, high glucose stress increased the apoptosis rate, while vitamin B3 reduced the apoptosis rate. The effect of vitamin B3 on autophagy flux under normal and high glucose stress was also investigated. Vitamin B3 increased the number of autophagosomes and increased the light chain (LC)3-II/LC3-I ratio. In contrast, vitamin B3 decreased sequestosome 1 (SQSTM1)/p62 protein expression and inhibited the phosphorylation of mammalian ribosomal protein S6 kinase β-1 (p70S6K/S6K1), which was a substrate of mammalian target of rapamycin (mTOR) under normal and high glucose stress. To further verify the protective effect of vitamin B3 on apoptosis, we treated islet β cell RIN-m5F with autophagy inhibitor 3-methyladenine (3-MA). Vitamin B3 decreased the apoptosis rate under high glucose stress, while the inhibition of apoptosis by vitamin B3 was blocked after adding 3-MA. Conclusion: Our data suggested that vitamin B3 reduced the apoptosis rate of β cells, possibly through inducing autophagy under high glucose stress. Abbreviations T2DMtype II diabetes mellitus T1DM type I diabetes mellitus AMPK AMP-activated protein kinase mTORC1 mTOR complex 1 mTORC2 mTOR complex 2 IGF1 insulin-like growth factor-1 PI3K phosphoinositide 3-kinase AKT protein kinase B KD Ketogenic diet

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“…Improvements in blood pressure, excessive bodyweight and lipid abnormalities are important for type 2 diabetes mellitus management to prevent and manage diabetes‐related complications, including CVD 5,6 . Two previous Japanese studies reported no significant differences in improvements in glycemic and coronary risk factors between SGLT2i and DPP4i treatments 25,26 . However, a recent Italian multicenter, retrospective, real‐world study reported that the proportion of patients achieving simultaneous reduction of HbA1c ≥0.5%, bodyweight ≥2 kg and SBP ≥2 mmHg was greater in patients newly starting dapagliflozin than those newly starting a DPP4i (17.6% vs 11.7%, relative risk 1.50, 95% CI 1.21, 1.86, P < 0.001) 15 .…”

Section: Discussionmentioning

confidence: 99%

Cardiometabolic risk reductions in patients with type 2 diabetes mellitus newly treated with a sodium–glucose cotransporter 2 inhibitor versus a dipeptidyl peptidase‐4 inhibitor: A real‐world administrative database study in Japan

Kashiwagi

Shoji

Kosakai

et al. 2022

J of Diabetes Invest

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Aims/Introduction Sodium–glucose cotransporter 2 inhibitors (SGLT2i) have shown beneficial effects on cardiometabolic risk factors (hemoglobin A1c, body mass index, systolic blood pressure) in patients with type 2 diabetes mellitus. We compared combined cardiometabolic effects of SGLT2i on hemoglobin A1c, body mass index and systolic blood pressure versus dipeptidyl peptidase‐4 inhibitors (DPP4i) in Japanese patients with type 2 diabetes mellitus. Materials and Methods This Japanese retrospective cohort study used the JMDC claims database. Patients newly treated with an SGLT2i (n = 18,936) or DPP4i (n = 55,484) were enrolled (January 2015–March 2020) and matched 1:1 using the propensity score. The primary end‐point was the proportion of patients achieving a composite outcome (i.e., simultaneous absolute/percent reduction in hemoglobin A1c ≥0.5%, body mass index ≥3% and systolic blood pressure ≥2 mmHg) 1 year after first SGLT2i or DPP4i prescription; Mantel–Haenszel common risk difference and its 95% confidence interval were estimated. Other end‐points included treatment persistence, with the associated hazard ratio calculated using the Cox proportional hazards model. Results After matching, patient characteristics were balanced (7,302 patients each). The proportion of patients achieving the composite outcome was significantly greater in patients receiving an SGLT2i than those receiving a DPP4i (31.0% [1,279/4,120] vs 12.9% [524/4,070], risk difference 18.6%, 95% confidence interval 16.3, 20.9, P < 0.001). Risk of treatment discontinuation was significantly lower in the SGLT2i group than in the DPP4i group (hazard ratio 0.85, 95% confidence interval 0.81, 0.90, P < 0.001). Conclusions In the present study, SGLT2i showed favorable cardiometabolic risk reduction and longer treatment persistence than DPP4i in Japanese patients with type 2 diabetes mellitus.

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A 52‐week randomized controlled trial of ipragliflozin or sitagliptin in type 2 diabetes combined with metformin: The N‐ISM study

Cited by 17 publications

References 35 publications

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Effects of Sitagliptin as Monotherapy and Add-On to Metformin on Weight Loss among Overweight and Obese Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis

Vitamin B3 inhibits apoptosis and promotes autophagy of islet β cells under high glucose stress

Cardiometabolic risk reductions in patients with type 2 diabetes mellitus newly treated with a sodium–glucose cotransporter 2 inhibitor versus a dipeptidyl peptidase‐4 inhibitor: A real‐world administrative database study in Japan

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