SGLT2 inhibitors provide an effective therapeutic option for diabetes complicated with insulin antibodies

Hayashi, Akinori; Takano, Koji; Kawai, Sayuki; Shichiri, Masayoshi

doi:10.1507/endocrj.ej15-0523

Cited by 11 publications

(8 citation statements)

References 9 publications

(10 reference statements)

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“…However, few studies have examined the additional effects of SGLT2 inhibitors during insulin therapy [ 1 – 3 ]. Furthermore, only two studies investigated diurnal changes using continuous glucose monitoring (CGM) [ 4 , 5 ]. SGLT2 inhibitors are effective in non-responders to conventional treatment or patients wishing to avoid weight gain because monotherapy with an SGLT2 inhibitor does not induce hypoglycemia [ 6 ] and these drugs decrease the body weight [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM)

et al. 2017

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IntroductionThe efficacy of administering a sodium–glucose cotransporter 2 inhibitor during insulin therapy has not been established. In this study, we examined its effects based on diurnal glycemic patterns using continuous glucose monitoring (CGM).MethodsThe subjects were 15 patients who had received insulin therapy for 1 year or more. A CGM device was attached to all subjects for 1 week. The administration of canagliflozin at 100 mg was started 4 days after attachment. The mean glucose concentrations, standard deviation (SD), mean amplitude of glycemic excursions (MAGE), mean of daily difference of blood glucose (MODD), and area under the curve (AUC) (≥180, <70 mg h/dL) after the start of administration were compared with the pretreatment values. In addition, we compared changes in the number of insulin units between basal and bolus insulin. Furthermore, we investigated the influence of canagliflozin on oxidative stress markers and cytokines using 8-hydroxy-2′-deoxyguanosine (8-OHdG), tumor necrosis factor-α (TNF-α), and adiponectin as parameters.ResultsThe mean glucose concentrations decreased from 161.1 to 139.1 mg/dL (P < 0.01). The SD decreased from 36.5 to 29.6 mg/dL (P = 0.05). The MAGE decreased from 89.2 to 77.4 mg/dL (P < 0.01), and the MODD decreased from 34.3 to 25.5 mg/dL (P < 0.05). All parameters showed significant improvements in diurnal changes. AUC of ≥180, i.e., the total area of blood glucose levels at or above 180 on the blood glucose curve of CGM, decreased from 339.1 to 113.6 mg/dL (P < 0.05). AUC of <70, i.e., the total area of blood glucose levels below 70 on the blood glucose curve of CGM, slightly decreased from 1.6 to 0.3 mg/dL (P = 0.08). The total number of basal insulin units decreased from 128 to 76, and that of bolus insulin decreased from 266 to 154; the dose of insulin could be markedly decreased. In addition, the mean 8-OHdG level decreased from 11.4 to 10.8 ng/mg Cre (P < 0.05), and the mean TNF-α level decreased from 2.31 to 1.79 pg/mL (P = 0.10). The mean adiponectin level increased from 5.01 to 5.53 μg/mL (P < 0.05).ConclusionCanagliflozin improved blood glucose changes in type 2 diabetes using insulin. In addition, the results suggest its antioxidant actions.Trial RegistrationUniversity Hospital Medical Information Network (UMIN no. 000019429).

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Section: Introductionmentioning

confidence: 99%

Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM)

et al. 2017

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“…In contrast to the large number of previous studies evaluating the efficacy of ipragliflozin by monitoring HbA1c or FPG levels [7][8][9][10][11] , only a limited number of studies have reported 24-h glucose profiles in the evaluation of ipragliflozin efficacy in improving glycemic control 13,14 . Likewise, as for other SGLT2 inhibitors, only a small number of clinical studies using CGM devices to investigate the effect of luseogliflozin [19][20][21] or sotagliflozin 22 on 24-h glucose profiles have been reported thus far.…”

Section: Discussionmentioning

confidence: 99%

“…Although treatment with SGLT2 inhibitors has been recommended for patients with type 2 diabetes mellitus who are relatively young and obese in daily clinical practice in Japan, the efficacy and safety of ipragliflozin for elderly or non‐obese patients are less clear, and there is a need to evaluate the drug based on patient background in a clinical setting. Furthermore, just a few studies that examined the impact of ipragliflozin as add‐on therapy to other OAM on 24‐h blood glucose profiles have been reported so far.…”

Section: Introductionmentioning

confidence: 99%

Efficacy of ipragliflozin as monotherapy or as add‐on therapy with other oral antidiabetic medications for treating type 2 diabetes in Japanese patients with inadequate glycemic control: A subgroup analysis based on patient characteristics

Osonoi

Nakamoto

Saito

et al. 2017

J of Diabetes Invest

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Aims/IntroductionThe aim of the present study was to evaluate the efficacy and safety of ipragliflozin in treating Japanese type 2 diabetes patients with inadequate glycemic control by investigating diurnal variations of blood glucose and body composition.Materials and MethodsThis was an investigator‐initiated, multicenter, prospective study with a 6‐month treatment period. The primary outcome investigated was change in hemoglobin A1c levels from baseline. Secondary outcomes included changes in fasting plasma glucose, insulin resistance, variations in 24‐h glucose levels detected by continuous glucose monitoring, bodyweight, body composition, waist circumference and serum lipids. Adverse events were evaluated throughout the study.ResultsA total of 98 patients completed the study. Over the 6‐month period, ipragliflozin‐treated patients showed reduction in hemoglobin A1c levels by 0.3%, fasting plasma glucose levels by 13.0 mg/dL, bodyweight by 2.1 kg, body fat mass by 1.5 kg and extracellular water by 0.3 kg, as well as a decrease in systolic/diastolic blood pressures. Significant reductions from baseline in mean amplitude of glucose excursions and standard deviation, and the reduced frequency of hyperglycemia were confirmed. High‐density lipoprotein cholesterol was also significantly improved. Notably, the subgroup analysis of hemoglobin A1c levels, bodyweight, waist circumference, and body composition based on age, sex and body mass index showed similar reductions within each subgroup. The incidences of adverse events and adverse drug reactions were 20.0% and 1.0%, respectively, over the 6‐month period.ConclusionsIpragliflozin is a useful oral antidiabetic medication for patients with a wide range of background characteristics.

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“…Pioglitazone and metformin have some beneficial effects on NAFLD, but their efficacy and safety have not been confirmed. Sodium–glucose cotransporter 2 inhibitors (SGLT2i) are a novel class of drug that reduces renal glucose reabsorption, lowers plasma glucose independent of insulin action and has some positive metabolic benefits. Empagliflozin and canagliflozin have been shown to reduce the incidence of cardiovascular events and delay the progression of kidney disease in patients with type 2 diabetes mellitus.…”

Section: Introductionmentioning

confidence: 99%

Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non‐alcoholic fatty liver disease

Inoue

Hayashi

Taguchi

et al. 2019

J of Diabetes Invest

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Aims/Introduction Non‐alcoholic fatty liver disease is frequently associated with type 2 diabetes, and constitutes an important risk factor for the development of hepatic fibrosis and hepatocellular carcinoma. Because there remains no effective drug therapy for non‐alcoholic fatty liver disease associated with type 2 diabetes, we evaluated the efficacy of sodium–glucose cotransporter 2 inhibitor. Methods and Materials In the present pilot, prospective, non‐randomized, open‐label, single‐arm study, we evaluated the effect of 100 mg canagliflozin administered once daily for 12 months on serological markers, body composition measured by bioelectrical impedance analysis method and hepatic fat fraction measured by magnetic resonance imaging in type 2 diabetes patients with non‐alcoholic fatty liver disease . Results Canagliflozin significantly reduced body and fat mass, and induced a slight decrease in lean body or muscle mass that did not reach significance at 6 and 12 months. Reductions in fat mass in each body segment (trunk, arms and legs) were evident, whereas those in lean body mass were not. The hepatic fat fraction was reduced from a baseline of 17.6 ± 7.5% to 12.0 ± 4.6% after 6 months and 12.1 ± 6.1% after 12 months ( P < 0.0005 and P < 0.005), whereas serum liver enzymes and type IV collagen concentrations improved. From a mean baseline hemoglobin A1c of 8.7 ± 1.4%, canagliflozin significantly reduced hemoglobin A1c after 6 and 12 months to 7.3 ± 0.6% and 7.7 ± 0.7% ( P < 0.0005 and P < 0.01). Conclusions Canagliflozin reduced body mass, fat mass and hepatic fat content without significantly reducing muscle mass.

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SGLT2 inhibitors provide an effective therapeutic option for diabetes complicated with insulin antibodies

Cited by 11 publications

References 9 publications

Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM)

Efficacy of Additional Canagliflozin Administration to Type 2 Diabetes Patients Receiving Insulin Therapy: Examination of Diurnal Glycemic Patterns Using Continuous Glucose Monitoring (CGM)

Efficacy of ipragliflozin as monotherapy or as add‐on therapy with other oral antidiabetic medications for treating type 2 diabetes in Japanese patients with inadequate glycemic control: A subgroup analysis based on patient characteristics

Effects of canagliflozin on body composition and hepatic fat content in type 2 diabetes patients with non‐alcoholic fatty liver disease

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