Comparison of efficacy and safety of insulin degludec/liraglutide and insulin glargine U-100/lixisenatide in individuals with type 2 diabetes mellitus using professional continuous glucose monitoring.

AIM/INTRODUCTION: Insulin glargine U100/lixisenatide and insulin degludec/liraglutide are fixed-ratio combinations containing basal insulin and a glucagon-like peptide-1 receptor agonist capable of reducing both fasting and postprandial blood glucose levels with a single formulation. This study aimed to compare the time in range (TIR) and the time below range (TBR) level 1 using professional continuous glucose monitoring and to establish criteria for the differential use of the fixed-ratio combinations. MATERIALS AND METHODS: Thirty-six outpatients with type 2 diabetes mellitus (24 men and 12 women; average age, 62.1 years) were randomly assigned to the groups. At 0 and 18 weeks, a device was worn to compare the TIR and TBR level 1. The correlation between the C-peptide index at baseline and TIR at 18 weeks was assessed. RESULTS: The TIR and TBR level 1 showed no significant differences between the two groups. Both groups showed significant positive correlations between the C-peptide index and the TIR (P = 0.002, r = 0.679; P = 0.002, r = 0.681, respectively). The changes in glycemic variability, therapeutic indices, and body mass index were not significantly different among the groups (P > 0.05). The receiver operating curve analysis revealed that the cut-off values of the C-peptide index to achieve TIR of >70% at 18 weeks were 1.258 (sensitivity, 77.8%; specificity, 100%) and 1.099 (sensitivity, 57.1%; specificity, 90.9%) in the insulin glargine U100/lixisenatide and insulin degludec/liraglutide groups, respectively. CONCLUSIONS: A TIR of >70% was achieved for both fixed-ratio combinations without significant differences.

Beneficial effects of luseogliflozin on lipid profile and liver function in patients with type 2 diabetes mellitus (BLUE trial): a single-center, single-arm, open-label prospective study.

BACKGROUND: Arteriosclerosis and non-alcoholic fatty liver disease are major complications of diabetes mellitus. Hyperglycemia, insulin resistance, obesity, and metabolic syndrome are associated with the progression of these complications. Sodium-glucose transporter 2 inhibitors such as luseogliflozin are oral hypoglycemic agents that reduce glucose levels, induce loss of weight or body fat, and improve liver function. However, the effects of these agents on lipid profiles are unclear. Therefore, this study aimed to investigate these effects and their relationship with arteriosclerosis and non-alcoholic fatty liver disease. METHODS: This single-center, single-arm, open-labeled prospective study enrolled 25 outpatients with type 2 diabetes mellitus who visited Minami Osaka Hospital. Laboratory tests and body measurements were performed at weeks 0 and 24. Luseogliflozin was started at 2.5 mg/day after breakfast, and data from weeks 0 and 24 were evaluated. There were no changes in the doses of other antidiabetic and dyslipidemia drugs a month prior to or during the study. RESULTS: The patients showed significant reductions in the levels of triglycerides, remnant-like particle cholesterol, and triglyceride/high-density lipoprotein cholesterol ratio, along with significant increases in the levels of high-density lipoprotein cholesterol and apolipoprotein A-1. Alanine aminotransferase, γ-glutamyl transpeptidase, and the fatty liver index were significantly reduced. CONCLUSIONS: Luseogliflozin-induced changes in the lipid profile were related to the suppression or improvement of arteriosclerosis and liver function, respectively. Patients who received this drug also showed improvements in the levels of liver enzymes and reductions in the fatty liver index. Earlier use of luseogliflozin might prevent diabetic complications. Trial registration This study was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000043595) on April 6th, 2021.

Polycythemia with elevated erythropoietin production in a patient with a urinary stone and unilateral hydronephrosis: a case report.

BACKGROUND: Absolute polycythemia can be primary or secondary. Erythropoietin-producing diseases (for example, hypoxia) are the major cause of secondary polycythemia. There are reports of polycythemia secondary to hydronephrosis. However, to our knowledge, there is no report on polycythemia secondary to hydronephrosis due to a urinary stone. Herein, we present a case of polycythemia with an elevated erythropoietin level in a patient with a urinary stone and unilateral hydronephrosis. CASE PRESENTATION: A 57-year-old Japanese man presented with polycythemia and an elevated erythropoietin level. Erythropoietin accumulation was not due to erythropoietin secretion by a tumor as no obvious lesions were detected on contrast-enhanced computed tomography. Abdominal ultrasonography revealed a stone in the left urinary tract and renal hydronephrosis, and 2 weeks later, the patient underwent transurethral ureterolithotripsy without complications. Blood tests 2 weeks after transurethral ureterolithotripsy showed that the erythropoietin level had declined. Hemoglobin concentration decreased from 20.8 mg/dL before and immediately after transurethral ureterolithotripsy to 15.8 mg/dL 3 months after transurethral ureterolithotripsy. This case was diagnosed as erythropoietin elevation due to unilateral hydronephrosis with a urinary stone, resulting in polycythemia. CONCLUSIONS: Hydronephrosis is a common disease but is not often associated with polycythemia. Further studies are required to elucidate the mechanism and implications of elevated erythropoietin production in hydronephrosis.

[Switching insulin degludec to insulin glulisine improved nocturnal hypoglycemia and ventricular arrythmia in an elderly type 1 diabetes patient with chronic heart failure: A case report].

The patient was 82-year-old man with type 1 diabetes mellitus. He had been using insulin degludec (IDeg) and insulin glulisine (IGlu) for treatment. He was admitted to our hospital due to diabetic ketoacidosis. As he started eating after recovery, we restarted intensive insulin therapy for glycemic control. Although he had eaten almost whole meals, his fasting blood glucose was extremely low, and the existence of nocturnal hypoglycemia was apparent. We reduced the dose and changed the injection time (evening→morning) of IDeg. We also stopped the evening IGlu injection; however, his nocturnal hypoglycemia did not improve. We decided to switch IDeg to insulin glargine U300 and to attach an intermittently scanned continuous glucose monitor (isCGM). His nocturnal hypoglycemia improved three days later. Since he had chronic heart failure and premature ventricular contractions, we used a Holter electrocardiogram to investigate the difference in arrythmia during hypoglycemia and non-hypoglycemia. As a result, the number of premature ventricular contractions was apparently high during hypoglycemia. In the present case, which involved an elderly patient with type 1 diabetes mellitus, chronic heart failure and nocturnal hypoglycemia, switching IDeg to insulin glargine U300 improved nocturnal hypoglycemia. IDeg differs from insulin glargine U300 in that it has a fatty acid side chain, which leads IDeg to combine with serum albumin. We thought that the increased level of free fatty acid due to hypoglycemia was competing against albumin combined IDeg, which increased free IDeg, and as a result, encouraged hypoglycemia.

Efficacy of IDegLira Versus IDegAsp Therapy in Patients with Type 2 Diabetes: A Randomized Crossover Study by isCGM.

INTRODUCTION: We aimed to compare the efficacy of insulin degludec/insulin aspart (IDegAsp) and insulin degludec/liraglutide (IDegLira) in controlling glucose fluctuation and suppressing postprandial glucose levels using intermittently scanned continuous glucose monitoring. METHODS: Twenty-four patients with type 2 diabetes mellitus were randomly allocated to receive either IDegLira or IDegAsp followed by IDegAsp or IDegLira, respectively. A crossover study was conducted with intermittently scanned continuous glucose monitoring. We compared the postprandial blood glucose level, time in range, and time below range from a 3-day intermittently scanned continuous glucose monitoring period for each treatment group. RESULTS: The time in range was significantly higher in IDegLira than in IDegAsp. Postprandial glucose levels 90 and 120 min after breakfast and 60, 90, and 120 min after lunch were significantly lower for IDegLira than for IDegAsp. However, postprandial glucose levels 90 and 120 min after supper were significantly lower for IDegAsp than for IDegLira. There was no significant difference in the time below range between IDegLira and IDegAsp. CONCLUSION: IDegLira was more effective in treating type 2 diabetes mellitus than IDegAsp, as indicated by a higher time in range and lower postprandial glucose level at breakfast and lunch. This study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000039221).

Adaptive support ventilation as an effective treatment option for central sleep apnea in an older adult with heart failure with preserved ejection fraction: a case report.

BACKGROUND: Adaptive support ventilation (ASV) is a proposed treatment option for central sleep apnea (CSA). Although the effectiveness of ASV remains unclear, some studies have reported promising results regarding the use of ASV in patients with heart failure with preserved ejection fraction (HfpEF). To illustrate the importance of suspecting and diagnosing sleep-disordered breathing (SDB) in older adults unable to recognize symptoms, we discuss a case in which ASV was effective in a patient with CSA and HfpEF, based on changes in the Holter electrocardiogram (ECG). CASE PRESENTATION: An 82-year-old man presented to our hospital with vomiting on April 19, 2021. Approximately 10 years before admission, he was diagnosed with type 1 diabetes mellitus and recently required full support from his wife for daily activities due to cognitive dysfunction. Two days before admission, his wife was unable to administer insulin due to excessively high glucose levels, which were displayed as "high" on the patient's glucose meter; therefore, we diagnosed the patient with diabetic ketoacidosis. After recovery, we initiated intensive insulin therapy for glycemic control. However, the patient exhibited excessive daytime sleepiness, and numerous premature ventricular contractions were observed on his ECG monitor despite the absence of hypoglycemia. As we suspected sleep-disordered breathing (SDB), we performed portable polysomnography (PSG), which revealed CSA. PSG revealed a central type of apnea and hypopnea due to an apnea-hypopnea index of 37.6, which was > 5. Moreover, the patient had daytime sleepiness; thus, we diagnosed him with CSA. We performed ASV and observed its effect using portable PSG and Holter ECG. His episodes of apnea and hypopnea were resolved, and an apparent improvement was confirmed through Holter ECG. CONCLUSION: Medical staff should carefully monitor adult adults for signs of or risk factors for SDB to prevent serious complications. Future studies on ASV should focus on older patients with arrhythmia, as the prevalence of CSA may be underreported in this population and determine the effectiveness of ASV in patients with HfpEF, especially in older adults.

Comparisons of efficacy and safety in insulin glargine and lixisenatide plus glulisine combination therapy with multiple daily injection therapy in Japanese patients with type 2 diabetes.

AIMS/INTRODUCTION: Multiple daily injection therapy for early glycemic control in patients with type 2 diabetes mellitus is associated with hypoglycemia and weight gain. This study aimed to compare the efficacy (time in range of glucose level 70-180 mg/dL), safety (time below range level 1 of glucose <70 mg/dL), glycemic variability changes, therapeutic indices, body mass index and titration periods between multiple daily injection and insulin glargine U100 and lixisenatide (iGlarLixi) combination (iGlarLixi + insulin glulisine; injected once daily [evenings]) therapies using intermittent continuous glucose monitoring. MATERIALS AND METHODS: A total of 40 hospitalized patients with type 2 diabetes were randomly assigned to the iGlarLixi + insulin glulisine group or the multiple daily injection group. An intermittent continuous glucose monitoring system was attached, and each injection was adjusted to achieve the target glucose level according to the respective titration algorithm. Times in and below the range were analyzed using data collected on days 11-13 of the intermittent continuous glucose monitoring. RESULTS: The time in range did not significantly differ between the groups. However, the time below range level 1 was lower in the iGlarLixi + insulin glulisine group (P = 0.047). The changes in glycemic variability, therapeutic indices and body mass index were not significantly different between the groups, although the titration period was significantly shorter in the iGlarLixi + insulin glulisine group (P = 0.033). CONCLUSIONS: iGlarLixi + insulin glulisine combination therapy is safe and equally efficacious as multiple daily injection therapy for glycemic control, while avoiding hypoglycemia risk and reducing the number of injections are required.