Glycaemic control efficacy of switching from dipeptidyl peptidase-4 inhibitors to oral semaglutide in subjects with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 2 study).

AIM: To assess whether oral semaglutide provides better glycaemic control, compared with dipeptidyl peptidase-4 inhibitor (DPP-4i) continuation, in people with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-label, prospective, randomized, parallel-group comparison study, participants receiving DPP-4is were either switched to oral semaglutide (3-14 mg/day) or continued on DPP-4is. The primary endpoint was the change in glycated haemoglobin (HbA1c) over 24 weeks. Secondary endpoints included changes in metabolic parameters and biomarkers, along with the occurrence of adverse events. Factors associated with HbA1c improvement were also explored. RESULTS: In total, 174 eligible participants were enrolled; 17 dropped out of the study. Consequently, 82 participants in the DPP-4i group and 75 participants in the semaglutide group completed the study and were included in the analysis. Improvement in HbA1c at week 24 was significantly greater when switching to semaglutide compared with DPP-4i continuation [-0.65 (95% confidence interval: -0.79, -0.51) vs. +0.05 (95% confidence interval: -0.07, 0.16) (p < .001)]. Body weight, lipid profiles and liver enzymes were significantly improved in the semaglutide group than in the DPP-4i continuation group. Multiple linear regression analysis revealed that baseline HbA1c and homeostasis model assessment 2-R were independently associated with HbA1c improvement after switching to semaglutide. Seven participants in the semaglutide group discontinued medication because of gastrointestinal symptoms. CONCLUSIONS: Although the potential for gastrointestinal symptoms should be carefully considered, switching from DPP-4is to oral semaglutide may be beneficial for glycaemic control and metabolic abnormalities in people with higher HbA1c and insulin resistance.

Improvement of glycaemic control and treatment satisfaction by switching from liraglutide or dulaglutide to subcutaneous semaglutide in patients with type 2 diabetes: A multicentre, prospective, randomized, open-label, parallel-group comparison study (SWITCH-SEMA 1 study).

AIM: To investigate the effects of switching from liraglutide or dulaglutide to once-weekly semaglutide on glycaemic control and treatment satisfaction in patients with type 2 diabetes. MATERIALS AND METHODS: In this multicentre, open-labelled, prospective, randomized, parallel-group comparison study, patients treated with liraglutide 0.9-1.8 mg/day (plan A) or dulaglutide 0.75 mg/week (plan B) were either switched to semaglutide or continued current therapy. The primary endpoint was the mean change in glycated haemoglobin over 24 weeks. The secondary endpoints included the changes of Diabetes Treatment Satisfaction Questionnaire scores, body weight and metabolic indices. RESULTS: In total, 110 patients were enrolled, and 10 were excluded; therefore, 37 patients in plan A and 63 patients in plan B completed the study. Glycated haemoglobin levels were significantly reduced in the semaglutide group in both plans [plan A, 7.8% ± 1.0% to 7.8% ± 0.7% (liraglutide) vs. 7.9% ± 0.7% to 7.3% ± 0.7% (semaglutide), p < .01; plan B, 7.8% ± 1.0% to 7.9% ± 1.2% (dulaglutide) vs. 7.8% ± 0.8% to 7.1% ± 0.6% (semaglutide), p < .01]. Semaglutide also improved Diabetes Treatment Satisfaction Questionnaire scores in both groups (plan A, +0.1 vs. +8.3, p < .01; plan B, -1.2 vs. +3.5, p < .01). Switching from dulaglutide yielded greater reductions in body weight and improved metabolic parameters. CONCLUSIONS: Once-weekly semaglutide administration improved glycaemic control and treatment satisfaction after switching from liraglutide or dulaglutide. These results highlighted a useful treatment option for patients with metabolic abnormalities despite glucagon-like receptor-1 receptor agonist treatment.

Add-on imeglimin versus metformin dose escalation regarding glycemic control in patients with type 2 diabetes treated with a dipeptidyl peptidase-4 inhibitor plus low-dose metformin: study protocol for a multicenter, prospective, randomized, open-label, parallel-group comparison study (MEGMI study).

INTRODUCTION: Imeglimin is a novel anti-hyperglycemic drug that improves both insulin resistance and insulin secretion. The effects of imeglimin on glycemic control were confirmed in phase III clinical trials, but little is known about its effectiveness in daily clinical practice settings, especially compared with metformin. Therefore, we aim to clarify the efficacy of imeglimin in patients with type 2 diabetes (T2D) being treated with a dipeptidyl peptidase-4 (DPP-4) inhibitor plus low-dose metformin. RESEARCH DESIGN AND METHODS: This is a multicenter, randomized, prospective, open-label, parallel-group trial. Seventy participants with T2D treated with a DPP-4 inhibitor plus metformin (500-1000 mg/day) for more than 12 weeks and a glycated hemoglobin (HbA1c) level of 52-85 mmol/mol (7.0%-9.9%) will be randomized to receive add-on imeglimin 1000 mg two times per day or metformin dose escalation for 24 weeks. Biochemical analyses and physical assessments will be performed at baseline and at the end of the study, and adverse events will be recorded. The primary endpoint is the change in HbA1c after 24 weeks. The secondary endpoints comprise the changes in blood pressure, pulse rate, body weight, abdominal circumference, and other laboratory parameters; the relationship between improvements of biological parameters including glycemic control and patient background characteristics; and side effects. RESULTS: This study will reveal new insights into the incorporation of imeglimin into the diabetes treatment strategy. CONCLUSIONS: This will be the first randomized controlled trial to compare the efficacy of adding imeglimin versus metformin dose escalation on glycemic control in patients with T2D. TRIAL REGISTRATION NUMBER: jRCT1011220005.

Effects of pemafibrate on lipid metabolism in patients with type 2 diabetes and hypertriglyceridemia: A multi-center prospective observational study, the PARM-T2D study.

AIMS: Pemafibrate, a novel selective peroxisome proliferator-activated receptor modulator, was shown to ameliorate lipid abnormalities in a phase III clinical trial of patients with type 2 diabetes mellitus (T2DM). However, its efficacy has not been demonstrated in real-world clinical practice in patients with T2DM. METHODS: We performed a multi-center prospective observational study of the use of pemafibrate in patients with T2DM and hypertriglyceridemia versus conventional therapy, with or without a fibrate. The primary outcomes were the changes from baseline in fasting serum triglyceride (TG) and high-density lipoprotein-cholesterol (HDL-C) concentrations at week 52. RESULTS: We recruited 650 patients, and data from 504 (252 per group) were analyzed after propensity score matching. In the pemafibrate group, both TG and HDL-C showed significant improvements (p < 0.001), and several indices reflecting TG-rich lipoproteins, low-density lipoprotein-cholesterol particle size, and liver enzyme elevations were significantly ameliorated compared with the control group, but there was no difference in glycemic control markers. One of the key secondary endpoints showed that switching from conventional fibrates to pemafibrate improved eGFR but increased uric acid concentration. CONCLUSIONS: In patients with T2DM, pemafibrate has superior effects on lipid profile as well as liver and renal dysfunction to conventional fibrates.

The agreement between measured HbA1c and optimized target HbA1c based on the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8): A cross-sectional study of elderly patients with diabetes.

AIM: To investigate the achievement of individualized target HbA1c based on the Japanese guideline after geriatric assessment with the Dementia Assessment Sheet for Community-based Integrated Care System 8-items (DASC-8) and to evaluate patient characteristics acting as barriers to achieving the target HbA1c in elderly outpatients with diabetes. METHODS: This cross-sectional study enrolled 303 Japanese outpatients aged ≥65 years with diabetes. Their health status was measured using the DASC-8. The target HbA1c was optimized for each patient by the guideline based on the DASC-8 score and use of drugs potentially associated with severe hypoglycemia. Patient characteristics related to the agreement between measured HbA1c and target HbA1c were extracted by multivariate logistic regression analysis. RESULTS: The mean age was 73.0 years and the mean body mass index (BMI) was 24.2 kg/m2 . The agreement between measured HbA1c and target HbA1c was 43.9% (95% confidence interval: 38.4%-50.0%). In multivariate logistic regression analysis, the agreement in patients with drugs potentially associated with severe hypoglycemia was significantly lower than in those without these drugs (37.8% vs. 60.5%, P = 0.0004). In patients with these drugs, higher BMI (P = 0.0271) and higher fasting plasma glucose (P = 0.0034) were independent related factors for measured HbA1c being higher than target HbA1c. Vulnerable elderly patients (P = 0.0116) and not taking sodium glucose co-transporter-2 (SGLT2) inhibitor (P = 0.0186) were independent related factors for inappropriately lower HbA1c. CONCLUSIONS: The agreement between measured HbA1c and target HbA1c was low in elderly patients with diabetes. Geriatr Gerontol Int 2022; 22: 560-567.

The renoprotective effect of once-weekly GLP-1 receptor agonist dulaglutide on progression of nephropathy in Japanese patients with type 2 diabetes and moderate to severe chronic kidney disease (JDDM67).

AIMS/INTRODUCTION: Few studies have investigated the renoprotective effect of glucagon-like peptide-1 (GLP-1) receptor in patients with chronic kidney disease (CKD). This study evaluated the effect of dulaglutide 0.75 mg on renal function in Japanese patients with type 2 diabetes and CKD stage 3 to 4. MATERIALS AND METHODS: Dulaglutide (group A) and non-dulaglutide (group B) were compared using data collected from a computerized diabetes care database. For group B, propensity score weighting based on propensity scores was performed. Evaluation items were a change from baseline in hemoglobin A1c (HbA1c), body weight, urine albumin-to-creatinine ratio (UACR), and estimated glomerular filtration rate (eGFR), for 3 years. RESULTS: In total, the data obtained from 255 patients (125 and 130 patients for group A and B, respectively) were analyzed. Propensity score-adjusted patient background characteristics (group A vs B) were age 70.8 vs 69.4 years, body weight 70.2 vs 72.9 kg, body mass index 27.3 vs 28.1 kg/m2 , HbA1c 8.4 vs 8.5%, eGFR 47.9 vs 47.7 mL/min/1.73 m2 , and UACR 218 vs 251 mg/gCr. Although there were no statistically significant differences in the change from baseline between groups A and B at most time points in eGFR, a statistically significant eGFR decline in group B was observed in slope analysis for 3 years. This renoprotective effect was marked in patients with macro-albuminuria and/or concomitant SGLT2 inhibitor use. CONCLUSIONS: Dulaglutide slowed the eGFR decline in patients with type 2 diabetes and CKD stage 3 to 4.

Effects of switching from a dipeptidyl peptidase-4 inhibitor to oral semaglutide on glucose metabolism in patients with type 2 diabetes: protocol for a multicentre, prospective, randomised, open-label, parallel-group comparison study (the SWITCH-SEMA 2 study).

INTRODUCTION: Incretin-based therapies exert antihyperglycaemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent fashion. The first-in-class oral glucagon-like peptide-1 receptor agonist semaglutide has potent effects on glycaemic and weight control, but little evidence has been published for the superiority of semaglutide for glycaemic control in patients after switching from a dipeptidyl peptidase-4 (DPP-4) inhibitor. Therefore, we aim to verify the efficacy of oral semaglutide in patients with T2D being treated with a DPP-4 inhibitor. METHODS AND ANALYSIS: This study is a multicentre, prospective, randomised, open-label, parallel-group trial. In total, 172 participants with T2D who have been treated with a DPP-4 inhibitor for more than 12 weeks and who have a glycated haemoglobin (HbA1c) level of 7.0%-9.9% will be randomised to continue using their existing DPP-4 inhibitor or switch to oral semaglutide for 24 weeks. Biochemical analyses and physical assessment will be performed, and adverse events will be recorded at baseline and at the end of the study. The primary endpoint will be the effect of oral semaglutide on the change in HbA1c. The secondary endpoints will be the mean changes in body weight, abdominal circumference, systolic and diastolic blood pressure (BP), pulse rate, the relationship between improvement of metabolic parameters including HbA1c and patient background characteristics, side effects and other laboratory parameters. ETHICS AND DISSEMINATION: This will be the first study to compare the effects of switching from a DPP-4 inhibitor to oral semaglutide on glycaemic control in patients with T2D. The results will be disseminated in peer-reviewed journals and at scientific conferences. Hokkaido University Certified Review Board (CRB no.1180001) has approved the protocol (no. 020-013). TRIAL REGISTRATION NUMBER: UMIN000045270 in the University Hospital Medical Information Network; jRCT1011210032 in the Japan Registry of Clinical Trials.

Do the benefits of sodium-glucose cotransporter 2 inhibitors exceed the risks in patients with type 1 diabetes?

Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are well-established means of improving glycemia and preventing cardio-renal events in patients with type 2 diabetes. However, their efficacy and safety have yet to be fully characterized in patients with type 1 diabetes (T1D). We studied patients with T1D who regularly attended one of five diabetes centers and treated with an SGLT2i (ipragliflozin or dapagliflozin) for >52 weeks, and the changes in HbA1c, body mass, insulin dose, and laboratory data were retrospectively evaluated and adverse events (AEs) recorded during December 2018 to April 2021. A total of 216 patients with T1D were enrolled during the period. Of these, 42 were excluded owing to short treatment periods and 15 discontinued their SGLT2i. The mean changes in glycated hemoglobin (HbA1c), body mass, and insulin dose were -0.4%, -2.1 kg, and -9.0%, respectively. The change in HbA1c was closely associated with the baseline HbA1c (p < 0.001), but not with the baseline body mass or renal function. The basal and bolus insulin doses decreased by 18.2% and 12.6%, respectively, in participants with a baseline HbA1c <8%. The most frequent AE was genital infection (2.8%), followed by diabetic ketoacidosis (DKA; 1.4%). None of the participants experienced severe hypoglycemic events. In conclusion, the administration of an SGLT2i in addition to intensive insulin treatment in patients with T1D improves glycemic control and body mass, without increasing the incidence of hypoglycemia or DKA.

Association between 25 Hydroxyvitamin D Concentrations and Lipid Profiles in Japanese with Type 2 Diabetes Mellitus.

Low 25 hydroxyvitamin D (25(OH)D) levels are closely associated with the risk of cardiovascular disease. Vitamin D deficiency is more common in patients with type 2 diabetes mellitus than in the general population. In addition, vitamin D status is lower in patients with the metabolic syndrome than in those without the syndrome. Therefore, we examined the association between lipid profiles and 25(OH)D levels. In this case control study, 285 type 2 diabetic patients who attended the Manda Memorial Hospital from March to October 2017 were selected and 25(OH)D, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglyceride (TG) levels, were obtained. Multiple regression analysis revealed that the association between 25(OH)D concentrations and TG levels was statistically significant (p<0.01) after adjusting for age, sex, body mass index, estimated glomerular flow rate (eGFR), insulin use, duration of diabetes mellitus, glycosylated hemoglobin (HbA1c), alcohol consumption, current smoking, and sampling timing. The serum 25(OH)D level was inversely associated with the TG level after the adjustment for the characteristics of Japanese patients with type 2 diabetes mellitus.

Efficacy and Safety of Low-Dose Pemafibrate Therapy for Hypertriglyceridemia in Patients with Type 2 Diabetes.

INTRODUCTION: Pemafibrate is a potent selective peroxisome proliferator-activated receptor α (PPARα) modulator that may be safer than conventional PPARα agonists in the treatment of dyslipidemia. This study was designed to investigate the efficacy of low-dose pemafibrate (0.1 mg/day) therapy for hypertriglyceridemia in 31 patients with type 2 diabetes and high triglyceride (TG) levels at the Manda Memorial Hospital. METHODS: TG, remnant lipoprotein cholesterol (RLP-C), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein (Apo) AI, Apo AII, Apo B, Apo CII, Apo CIII, and Apo E levels were evaluated. Liver, kidney, and muscle toxicity tests were also performed. Pemafibrate (0.1 mg) was administered once daily. RESULTS: This treatment significantly decreased TG, RLP-C, Apo CII, Apo CIII, and Apo E levels while significantly increasing HDL-C, Apo AI, and Apo AII levels. No significant changes were observed in LDL-C and Apo B levels. There were no significant liver-, kidney-, or muscle-related adverse events. CONCLUSIONS: The results of this study show that low-dose pemafibrate administration improves the lipid profile in Japanese patients with hypertriglyceridemia and type 2 diabetes.

Effects of Switching from Liraglutide or Dulaglutide to Subcutaneous Semaglutide on Glucose Metabolism and Treatment Satisfaction in Patients with Type 2 Diabetes: Protocol for a Multicenter, Prospective, Randomized, Open-Label, Blinded-Endpoint, Parallel-Group Comparison Study (The SWITCH-SEMA 1 Study).

INTRODUCTION: Glucagon-like peptide (GLP)-1 receptor agonists exert potent hypoglycemic effects in patients with type 2 diabetes (T2D) in a blood glucose concentration-dependent manner. Once-weekly subcutaneous administration of the GLP-1 receptor agonist semaglutide has beneficial effects on glycemic and body weight control, but it is currently unclear if semaglutide provides superior glycemic control compared to conventional GLP-1 receptor agonists in the Japanese population. We aim to compare the effects of once-weekly subcutaneous semaglutide with those of liraglutide or dulaglutide administration in Japanese patients with T2D. METHODS: This study is a multicenter, prospective, randomized, open-label, blinded-endpoint, parallel-group trial. In total, 100 participants with T2D who have been treated with liraglutide (0.9-1.8 mg/day in plan A) or dulaglutide (0.75 mg/week in plan B) for more than 12 weeks and have a glycated hemoglobin (HbA1c) level of 6.0-9.9% and a body mass index (BMI) of ≥ 22 kg/m2 will be randomized to either continue using their existing GLP-1 receptor agonist or switch to subcutaneous semaglutide once weekly for 24 weeks. Biochemical analysis, physical assessment, and a quality-of-life questionnaire (DTSQ) will be completed at baseline and at the end of the study. The primary endpoint is the effect of semaglutide on the change in HbA1c. The secondary endpoints are the mean changes in total DTSQ score, body mass, abdominal circumference, systolic and diastolic blood pressure, pulse rate, factors associated with improvement in HbA1c and secondary endpoints, side effects, and other laboratory parameters. PLANNED OUTCOMES: The results of the study will provide useful information regarding the effects of switching to semaglutide from other GLP-1 receptor agonists on glycemic control in patients with T2D. ETHICS AND DISSEMINATION: The Hokkaido University Certified Review Board (CRB no. 1180001) has approved the protocol (no. 018-005). The results will be disseminated in peer-reviewed journals and at scientific conferences. TRIAL REGISTRATION: UMIN000042369 in the University Hospital Medical Information Network (UMIN); jRCT1011200008 in the Japan Registry of Clinical Trials (jRCT); pre-results.

Improved time in range and postprandial hyperglycemia with canagliflozin in combination with teneligliptin: Secondary analyses of the CALMER study.

AIMS/INTRODUCTION: We recently reported the beneficial effect of the combination of sodium-glucose cotransporter 2 inhibitor and dipeptidyl peptidase-4 inhibitor on daily glycemic variability in patients with type 2 diabetes mellitus. Additional favorable effects of combination therapy were explored in this secondary analysis. MATERIALS AND METHODS: The CALMER study was a multicenter, open-label, prospective, randomized, parallel-group comparison trial for type 2 diabetes mellitus involving continuous glucose monitoring under meal tolerance tests. Patients were randomly assigned to switch from teneligliptin to canagliflozin (SWITCH group) or to add canagliflozin to teneligliptin (COMB group). The continuous glucose monitoring metrics, including time in target range, were investigated. RESULTS: All 99 participants (mean age 62.3 years; mean glycated hemoglobin 7.4%) completed the trial. The time in target range was increased in the COMB group (71.2-82.7%, P < 0.001). The extent of the reduction in time above target range was significantly larger in the COMB group compared with the SWITCH group (-14.8% vs -7.5%, P < 0.01). Area under the curve values for glucose at 120 min after all meal tolerance tests were significantly decreased in the COMB group compared with the SWITCH group (P < 0.05). CONCLUSIONS: Sodium-glucose cotransporter 2 inhibitor combined with dipeptidyl peptidase-4 inhibitor improved the quality of glycemic variability and reduced postprandial hyperglycemia compared with each monotherapy.

Favorable effect of sodium-glucose cotransporter 2 inhibitor, dapagliflozin, on non-alcoholic fatty liver disease compared with pioglitazone.

AIMS/INTRODUCTION: Sodium-glucose cotransporter 2 inhibitors, as well as thiazolidines, suppress nonalcoholic fatty liver disease (NAFLD); however, few comparative studies have been reported. Dapagliflozin has shown non-inferiority compared with pioglitazone for glycemic control, and superiority regarding weight reduction in patients with type 2 diabetes. We carried out a secondary analysis for the favorable effects of sodium-glucose cotransporter inhibitors for NAFLD. MATERIALS AND METHODS: In this multicenter, open-label, prospective, randomized, parallel-group comparison trial, patients taking pioglitazone for ≥12 weeks were randomly switched to dapagliflozin or continued pioglitazone for a further 24 weeks. The fatty liver index (FLI), consisting of body mass index, triglycerides, waist circumference and γ-glutamyl transpeptidase, was used for the evaluation of NAFLD. RESULTS: A total of 53 participants with NAFLD (27 dapagliflozin; 26 pioglitazone) were included in this analysis. FLI decreased significantly in the dapagliflozin group (48.7 ± 23.4 to 42.1 ± 23.9) compared with the pioglitazone group (49.0 ± 26.1 to 51.1 ± 25.8; P < 0.01). Multiple linear regression analysis showed that the changes in FLI had a significantly positive correlation with changes in glycated hemoglobin (P = 0.03) and insulin level (P < 0.01) in the dapagliflozin group. CONCLUSION: Dapagliflozin might be more beneficial than pioglitazone in patients with NAFLD. Improvements in FLI would be closely related to glycemic control.

Impact of endogenous insulin secretion on the improvement of glucose variability in Japanese patients with type 2 diabetes treated with canagliflozin plus teneligliptin.

AIMS/INTRODUCTION: To identify the effect of combination therapy with a dipeptidyl peptidase-4 inhibitor and a sodium-glucose cotransporter 2 inhibitor compared with switching from a dipeptidyl peptidase-4 inhibitor to a sodium-glucose cotransporter 2 inhibitor on improving the glucose variability in patients with or without impaired endogenous insulin secretion. MATERIALS AND METHODS: A secondary analysis regarding the relationship between endogenous insulin secretion and the change in mean amplitude of glycemic excursions (ΔMAGE) was carried out in a multicenter, prospective, randomized, parallel-group comparison trial that enrolled patients with type 2 diabetes who had been taking teneligliptin and were treated by switching to canagliflozin (SWITCH) or adding canagliflozin (COMB). Participants were categorized into the following four subgroups: SWITCH or COMB and high or low fasting C-peptide (CPR) divided at baseline by the median. RESULTS: ΔMAGE in the COMB group was greatly improved independent of a high or low CPR (-29.2 ± 28.3 vs -20.0 ± 24.6, respectively; P = 0.60). However, ΔMAGE was not ameliorated in the low CPR SWITCH group, and the ΔMAGE was significantly smaller than that in the high CPR COMB group (P < 0.01). CONCLUSIONS: COMB would be a better protocol rather than switching teneligliptin to canagliflozin to improve daily glucose variability in patients with impaired endogenous insulin secretion.

Ultrasonography Improves Glycemic Control by Detecting Insulin-Derived Localized Amyloidosis.

We examined the feasibility of ultrasound diagnosis of insulin-derived localized amyloidosis (IDLA). In addition to ultrasound detectability and findings, the insulin absorption rate, insulin dosage and hemoglobin A1c (HbA1c) levels before and after shifting the insulin injection site were investigated for 22 cases of IDLA. The detectability of IDLA on ultrasound was 100%; 59.1% was palpable lumps and 40.9% was not palpable. The palpable type had lower echo intensity and were harder than the non-palpable type. Blood flow decreased in IDLA, especially in the palpable type. IDLA, especially the palpable type, had a low insulin absorption rate. HbA1c level and insulin dosage decreased after shifting the injection site. The palpable type had more insulin reduction than the non-palpable type. Characteristic ultrasound images of IDLA were acquired. As the non-palpable type could be identified by ultrasound, its diagnosis encourages changing the insulin injection site; hence, ultrasound diagnosis of IDLA can enhance insulin treatment.

Insulin degludec/insulin aspart versus biphasic insulin aspart 30 twice daily in insulin-experienced Japanese subjects with uncontrolled type 2 diabetes: Subgroup analysis of a Pan-Asian, treat-to-target Phase 3 Trial.

BACKGROUND: The present study was a subgroup analysis of a Pan-Asian Phase 3 open-label randomized treat-to-target trial evaluating insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) in Japanese subjects with type 2 diabetes inadequately controlled on insulin. METHODS: Eligible subjects (n = 178) were randomized (2: 1) to twice-daily (b.i.d.) IDegAsp or BIAsp 30 with or without metformin for 26 weeks, titrated to a blood glucose target of between 3.9 and <5.0 mmol/L. Changes in HbA1c , the proportion of responders reaching the HbA1c target, and changes in fasting plasma glucose, nine-point self-monitored plasma glucose profiles, and body weight were assessed. RESULTS: At 26 weeks, the decrease in HbA1c was similar in both groups. Fasting plasma glucose was lower with IDegAsp than BIAsp 30 (estimated treatment difference -1.50 mmol/L; 95 % confidence interval [CI] -1.98, -1.01). Overall confirmed hypoglycemia rates were similar; the nocturnal confirmed hypoglycemia rate was lower with IDegAsp than BIAsp 30 (estimated rate ratio 0.44; 95 % CI 0.20, 0.99). No severe hypoglycemic episodes were reported. CONCLUSIONS: The results indicate that IDegAsp b.i.d. improves glycemic control and, compared with BIAsp 30, lowers the rate of nocturnal confirmed hypoglycemia.

Localized Subcutaneous Insulin-Derived Amyloidosis Excised after Evaluation Using Ultrasonography in a Patient with Type 2 Diabetes Mellitus.

A 62-year-old man with type 2 diabetes mellitus, who had been on insulin therapy for the past 20 years, was found to have subcutaneous mass formation in the abdomen during a workup of worsened glycemic control. Because of suspected amyloid deposition, he was advised to avoid injections to the mass, which led to improvement of glycemic control. However, he strongly requested mass excision and was hospitalized. After evaluation using ultrasonography and computed tomography, a total mass excision was performed, and a diagnosis of insulin-derived amyloidosis was made. Comparison of the ultrasonographic and histopathological findings demonstrated that the location of the amyloid deposition nearly corresponded to the hypoechoic region. This case highlights that ultrasonography, which is a noninvasive imaging modality, can be useful for detection of insulin-derived amyloidosis.

Insulin degludec/insulin aspart versus biphasic insulin aspart 30 in Asian patients with type 2 diabetes inadequately controlled on basal or pre-/self-mixed insulin: a 26-week, randomised, treat-to-target trial.

AIMS: Insulin degludec/insulin aspart (IDegAsp) is a soluble co-formulation of IDeg and IAsp. This pan-Asian, 26-week trial investigated efficacy and safety of IDegAsp vs biphasic insulin aspart 30 (BIAsp 30) in Asian adults with type 2 diabetes (T2DM), inadequately controlled on once- or twice-daily (BID) basal, premixed or self-mixed insulin. METHODS: Participants (mean age 59.8 years, HbA1c 8.4%, FPG 7.9 mmol/L, BMI 25.4 kg/m(2)) were randomised 2:1 to BID IDegAsp (n=282) or BIAsp 30 (n=142) and continued existing metformin treatment. Insulins were administered with breakfast and main evening meal, titrated to a pre-breakfast and pre-main evening meal self-measured plasma glucose target of 4-5 mmol/L. RESULTS: IDegAsp achieved the primary endpoint of non-inferiority to BIAsp 30 for mean change in HbA1c (estimated treatment difference [ETD] IDegAsp-BIAsp 30: 0.05% points [95% CI -0.10; 0.20]). IDegAsp was superior in lowering fasting plasma glucose (FPG) (ETD -1.06 mmol/L, 95% CI -1.43; -0.70, p<0.001), and resulted in a lower final mean daily insulin dose (0.79 U/kg vs 0.99 U/kg, estimated rate ratio [RR] 0.79, 95% CI 0.73; 0.85, p<0.0001). Rates of overall confirmed and severe hypoglycaemia were similar between treatments, while rate of nocturnal confirmed hypoglycaemia was numerically (p=ns) lower with IDegAsp. During the maintenance period there was a trend (p=ns) towards lower hypoglycaemia rates for IDegAsp. CONCLUSION: In Asian adults with T2DM, IDegAsp BID effectively improves long-term glycaemic control, and compared to BIAsp 30, provides superior reductions in FPG with a lower dose, and numerically less nocturnal hypoglycaemia.

Effect of nanoparticle-rich diesel exhaust on testicular and hippocampus steroidogenesis in male rats.

BACKGROUND: Nanoparticle-rich diesel exhaust (NR-DE) has potentially adverse effects on testicular steroidogenesis. However, it is unclear whether NR-DE influences steroidogenic systems in the brain. OBJECTIVE: To investigate the effect of NR-DE on hippocampal steroidogenesis of adult male rats in comparison with its effect on the testis. METHODS: F344 male rats (8-week-old) were randomly divided into four groups (n = 8 or 9 per group) and exposed to clean air with 4.6 ± 3.2 µg/m(3) in mass concentration, NR-DE with 38 ± 3 µg/m(3) (a level nearly equivalent to the environmental standard in Japan (low NR-DE)), NR-DE with 149 ± 8 µg/m(3) (high NR-DE), or filtered diesel exhaust with 3.1 ± 1.9 µg/m(3) (F-DE), for 5 hours/day, 5 days/week, for 1, 2 or 3 months. F-DE was prepared by removing only particulate matters from high NR-DE with an HEPA filter. RESULTS: Exposures to the high NR-DE for 1 month, and low NR-DE for 2 months, significantly increased or tended to increase plasma and testicular testosterone levels compared to clean air exposure, which might have resulted from the increased expression of mRNA of steroidogenic acute regulatory protein and its protein in the testes of rats. In the hippocampus, high NR-DE exposure for 1 month significantly increased the androstendione level compared to the clean air exposure, while no significant difference was observed in the steroidogenesis between fresh air exposure and any exposure to NR-DE or F-DE. CONCLUSION: NR-DE may influence steroidogenic enzymes in the testis, but not those in the hippocampus.