OBJECTIVES

Blood glucose levels of the majority of Filipino patients with type 2 diabetes (T2D) remain uncontrolled. Insulin degludec/insulin aspart (IDegAsp) is a fixed‑ratio coformulation of the long‑acting basal insulin degludec and the rapid acting prandial insulin aspart. The realworld ARISE (A Ryzodeg® Initiation and Switch Effectiveness) study investigated clinical outcomes across six countries in people with T2D who initiated IDegAsp. This publication presents the clinical outcomes of the Filipino cohort from a subgroup analysis of the ARISE study.

METHODOLOGY

This 26-week, openlabel, noninterventional study examined outcomes in adults with T2D initiating or switching to IDegAsp (N=185) from other antidiabetic treatments per local clinical guidance.

RESULTS

Compared with the baseline, there was a significant improvement in glycated hemoglobin at the end of the study (EOS) (estimated difference [ED] −1.4 [95% confidence interval −1.7, −1.1]; P < 0.0001). Fasting plasma glucose (ED −46.1 mg/dL [−58.2, −34.0]; P < 0.0001) and body weight (ED −1.0 kg [−2.0, −0.1]; P = 0.028) were significantly reduced at EOS compared with baseline. IDegAsp was associated with a decrease in the incidence of selfreported healthcare resource utilization. Adverse events were reported in eight (4.3%) participants.

CONCLUSION

Initiating or switching to IDegAsp was associated with improved glycemic control, lower body weight, and lower HRU for people with T2D in the Philippines. No new, unexpected AEs were reported.

Human ; Insulin Aspart ; Insulin Degludec ; Diabetes Mellitus, Type 2

Insulin degludec/insulin aspart (IDegAsp) co-formulation provides both basal and mealtime glycaemic control in a single injection. The glucose level-lowering efficacy of IDegAsp is reported to be superior or non-inferior to that of the currently available insulin therapies with a lower rate of overall hypoglycaemia and nocturnal hypoglycaemia. An expert panel from Malaysia aims to provide insights into the utilisation of IDegAsp across a broad range of patients with type 2 diabetes mellitus (i.e. treatment-naïve or insulin-naïve patients or patients receiving treatment intensification from basal-only regimens, premixed insulin and basal–bolus insulin therapy). IDegAsp can be initiated as once-daily dosing for the main meal with the largest carbohydrate content with weekly dose adjustments based on patient response. A lower starting dose is recommended for patients with cardiac or renal comorbidities. Dose intensification with IDegAsp may warrant splitting into twice-daily dosing. IDegAsp twice-daily dosing does not need to be split at a 50:50 ratio but should be adjusted to match the carbohydrate content of meals. The treatment of patients choosing to fast during Ramadan should be switched to IDegAsp early before Ramadan, as a longer duration of titration leads to better glycated haemoglobin level reductions. The pre-Ramadan breakfast/lunch insulin dose can be reduced by 30%–50% and taken during sahur, while the pre-Ramadan dinner dose can be taken without any change during iftar. Education on the main meal concept is important, as carbohydrates are present in almost all meals. Patients should not have a misconception of consuming more carbohydrates while taking IDegAsp.
insulin degludec [Supplementary Concept] ; Insulin Aspart ; Glucose ; Hypoglycaemia ; Diabetes Mellitus, Type 2

BACKGROUND: The prevalence of type 2 diabetes mellitus (T2DM) and obesity is increasing in Korea. Clinical studies in patients with T2DM have shown that combining the glucagon-like peptide-1 receptor agonist exenatide twice daily with basal insulin is an effective glucose-lowering strategy. However, these studies were predominantly conducted in non-Asian populations. METHODS: We conducted a subgroup analysis of data from a multinational, 30-week, randomized, open-label trial to compare the effects of exenatide twice daily (n=10) or three times daily mealtime insulin lispro (n=13) among Korean patients with T2DM inadequately controlled (glycosylated hemoglobin [HbA1c] >7.0%) on metformin plus optimized insulin glargine. RESULTS: Exenatide twice daily and insulin lispro both reduced HbA1c (mean −1.5% and −1.0%, respectively; P<0.01 vs. baseline). Fasting glucose and weight numerically decreased with exenatide twice daily (−0.7 mmol/L and −0.7 kg, respectively) and numerically increased with insulin lispro (0.9 mmol/L and 1.0 kg, respectively). Minor hypoglycemia occurred in four patients receiving exenatide twice daily and three patients receiving insulin lispro. Gastrointestinal adverse events were the most common with exenatide twice daily treatment. CONCLUSION: This analysis found treatment with exenatide twice daily improved glycemic control without weight gain in Korean patients with T2DM unable to achieve glycemic control on metformin plus basal insulin.
Diabetes Mellitus, Type 2* ; Fasting ; Glucagon-Like Peptide-1 Receptor ; Glucose ; Humans ; Hypoglycemia ; Insulin Glargine ; Insulin Lispro* ; Insulin* ; Korea ; Meals ; Metformin ; Obesity ; Prevalence ; Weight Gain

BACKGROUND: This is part of a prospective study carried out as a national project to secure standardized public resources for type 2 diabetes mellitus (T2DM) patients in Korea. We compared various characteristics of long-standing T2DM patients with diabetic retinopathy (DR) and macular edema (ME). METHODS: From September 2014 to July 2015, T2DM patients with disease duration of at least 15 years were recruited at a single university hospital. Clinical data and samples were collected according to the common data elements and standards of procedure developed by the Korean Diabetes Association Research Council. Each participant was assessed by ophthalmologists for DR and ME. RESULTS: Among 220 registered patients, 183 completed the ophthalmologic assessment. DR was associated with longer disease duration (odds ratio [OR], 1.071; 95% confidence interval [CI], 1.001 to 1.147 for non-proliferative diabetic retinopathy [NPDR]) (OR, 1.142; 95% CI, 1.051 to 1.242 for proliferative diabetic retinopathy [PDR]) and the use of long-acting insulin (OR, 4.559; 95% CI, 1.672 to 12.427 for NPDR) (OR, 4.783; 95% CI, 1.581 to 14.474 for PDR), but a lower prevalence of a family history of cancer (OR, 0.310; 95% CI, 0.119 to 0.809 for NPDR) (OR, 0.206; 95% CI, 0.063 to 0.673 for PDR). ME was associated with higher glycosylated hemoglobin levels (OR, 1.380; 95% CI, 1.032 to 1.845) and the use of rapid-acting insulin (OR, 5.211; 95% CI, 1.445 to 18.794). CONCLUSION: Various clinical features were associated with DR and ME. Additional epidemiological and biorepository-based studies using this cohort are being conducted to deepen our understanding of diabetic complications in Korea.
Cohort Studies ; Common Data Elements ; Diabetes Complications ; Diabetes Mellitus, Type 2* ; Diabetic Retinopathy* ; Hemoglobin A, Glycosylated ; Humans ; Insulin, Long-Acting ; Insulin, Short-Acting ; Korea ; Macular Edema ; Prevalence ; Prospective Studies

INTRODUCTION: Diabetic ketoacidosis (DKA) remains a significant complication of diabetes in the world and is associated with high rates of hospital admissions. In mild, uncomplicated cases of DKA a subcutaneous regimen of newer rapid-acting insulin analogues has been proposed as a safe and effective alternative to intravenous regular insulin in prospective, randomized trials. Our primary objective is to compare the efficacy and safety of intermittent subcutaneous (SC) rapid insulin administration with continuous intravenous (IV) regular insulin infusion in the treatment of mild to moderate DKA.

METHODOLOGY: A retrospective chart review of all adult Filipino patients admitted for mild to moderate DKA at UST Hospital private and clinical divisions from 2012 - 2015 was done. Chart cases were divided into two groups, namely:group one who received IV infusion of regular insulin and group two who received SC rapid insulin analog astreatment. The clinical and biochemical characteristics of the patients on admission were obtained. Efficacy and safety of both treatment regimens were compared as to the duration of time and amount of insulin administered from admission until resolution of DKA was achieved, occurrence of hypoglycemia and hypokalemia, mortality and length of hospitalization.

RESULTS: Twenty-one chart cases were included, twelve in the continuous IV insulin infusion group and nine in the intermittent SC rapid insulin group. The baseline characteristics of patients were almost similar. There was no significant difference between the treatment groups in the duration of time and amount of insulin administered to achieve DKA resolution, occurrence of hypoglycemia, and death. Hypokalemia occurred more frequently and hospital stay was longer in the IV insulin group.

CONCLUSION: Intermittent subcutaneous rapid insulin regimen is an effective, safe, and potentially cost-effective alternative to continuous intravenous insulin infusion for treatment of mild to moderate cases of DKA.

Human ; Male ; Female ; Adult ; Insulin, Short-acting ; Diabetic Ketoacidosis ; Insulin ; Hypokalemia ; Hypoglycemia ; Hospitalization ; Infusions, Intravenous ; Safety

INTRODUCTION: In the management of type 2 diabetes, insulin is often started late, when there is failure to achieve good control on maximum oral agents. Clinical inertia to insulin initiation and intensification is widely prevalent in our local setting resulting in poor control of diabetes. This study looked into a stepwise insulin combinations treatment algorithm used in an Endocrinology referral clinic at the University of Santo Tomas Hospital (USTH). It aimed to demonstrate the clinical course of the patients , determine the degree of HbA1c reduction, and show the associated extent of hypoglycemia and weight gain.

METHODS: This is a retrospective chart review of 104 patients that used the following stepwise treatment: Oral regimen; Regimen A: basal+oral; Regimen B: basal+premeal bolus TID±oral; Regimen C: premixed aspart 70/30 or lispro 75/25 TID or BID with prelunch bolus, ± oral; Regimen D: premixed 70/30 BID+premeal bolus TID ± oral; Regimen E: premixed 70/30 BI +premeal bolus TID+basal ±oral. All received automatic snacking two hours after main meals to prevent hypoglycemia. Patients were educated on proper diet and exercise. Data was analyzed using paired t-test, frequencies and percentages.

RESULTS: Most ended on the intensive insulin regimens D 57(55%), and E 18 (17%). Significant HbA1c reduction was demonstrated as follows: Regimen A (n=8):1.376±0.919 (p=0.000), Regimen B (n=18):2.320±2.177 (p=0.000), Regimen D (n=57):2.197±2.158 (p=0.000), Regimen E (n=18):2.684±1.689 (p =0.000). Overall mean weight gain was 1.070 ± 11.435 kg (p=0.335). Ten, nonsevere hypoglycemia events were reported.

CONCLUSION: The use of this stepwise insulin combinations treatment algorithm exerted significant HbA1c reduction, with minimal events of hypoglycemia, and statistically insignificant weight gain. Hence, this is a feasible tool that may be used as a guide for intensification of insulin treatment.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Insulin Lispro ; Insulin ; Diabetes Mellitus, Type 2 ; Regimen B ; Weight Gain ; Hypoglycemia ; Antineoplastic Combined Chemotherapy Protocols ; Diet ; Algorithms

Increased plasma insulin levels are often observed in exogenous insulin overdose patients. However, plasma insulin level may decrease with time. We report a case of low plasma insulin level hypoglycemia after insulin lispro overdose. The patient was a 37-year-old man with no previous medical history who suspected insulin lispro overdose. Upon arrival, his Glasgow coma scale was 3 points and his blood sugar level (BSL) was 24 mg/dl. We found five humalog-quick-pen (insulin lispro) in his bag. There was no elevation of glucose level, despite an initial 50 ml bolus of 50% glucose and 150 cc/hr of 10% dextrose continuous intravenous infusion. He also suffered from generalized tonic-clonic seizure, which was treated with lorazepam and phenytoin. We conducted endotracheal intubation, after which he was admitted to the intensive care unit (ICU). There were recurrent events of hypoglycemia below BSL<50 mg/dl after admission. We repeatedly infused 50 ml 50% glucose 10 times and administered 1 mg of glucagon two times. The plasma insulin level was 0.2 uU/ml on initial blood sampling and 0.2 uU/ml after 5 hours. After 13 hours, his BSL stabilized but his mental status had not recovered. Diffuse brain injury was observed upon magnetic resonance imaging (MRI) and severe diffuse cerebral dysfunction was found on electroencephalography (EEG). Despite 35 days of ICU care, he died from ventilator associated pneumonia.
Adult ; Blood Glucose ; Brain Injuries ; Electroencephalography ; Glasgow Coma Scale ; Glucagon ; Glucose ; Humans ; Hypoglycemia* ; Infusions, Intravenous ; Insulin Lispro* ; Insulin* ; Intensive Care Units ; Intubation, Intratracheal ; Lorazepam ; Magnetic Resonance Imaging ; Phenytoin ; Plasma* ; Pneumonia, Ventilator-Associated ; Seizures

The incidence of type 1 diabetes is increasing worldwide, and the greatest increase has been observed in very young children under 4 years of age. A case of infantile diabetic ketoacidosis in a 10-month-old male infant was encountered by these authors. The infant's fasting glucose level was 490 mg/dL, his PH was 7.13, his pCO₂ was 15 mmHg, and his bicarbonate level was 5.0 mmol/L. The glycosylated hemoglobin level had increased to 9.4%. Ketonuria and glucosuria were detected in the urinalysis. The fasting C-peptide and insulin levels had decreased. The infant was positive for anti-insulin and antiglutamic acid decarboxylase antibodies. Immediately after the infant's admission, fluid therapy and intravenous insulin infusion therapy were started. On the second day of the infant's hospitalization and after fluid therapy, he recovered from his lethargic condition, and his general condition improved. Feeding was started on the third day, and he was fed a formula 5 to 7 times a day and ate rice, vegetables, and lean meat. Due to the frequent feeding, the frequency of rapid-acting insulin injection was increased from 3 times before feeding to 5 times, adjusted according to the feeding frequency. The total dose of insulin that was injected was 0.8-1.1 IU/kg/day, and the infant was discharged on the 12th day of his hospitalization. The case is presented herein with a brief review of the relevant literature.
Antibodies ; C-Peptide ; Child ; Diabetes Mellitus, Type 1* ; Diabetic Ketoacidosis* ; Fasting ; Fluid Therapy ; Glucose ; Hemoglobin A, Glycosylated ; Hospitalization ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Infant* ; Insulin* ; Insulin, Short-Acting ; Ketosis ; Male ; Meat ; Urinalysis ; Vegetables

The incidence of type 1 diabetes is increasing worldwide, and the greatest increase has been observed in very young children under 4 years of age. A case of infantile diabetic ketoacidosis in a 10-month-old male infant was encountered by these authors. The infant's fasting glucose level was 490 mg/dL, his PH was 7.13, his pCO₂ was 15 mmHg, and his bicarbonate level was 5.0 mmol/L. The glycosylated hemoglobin level had increased to 9.4%. Ketonuria and glucosuria were detected in the urinalysis. The fasting C-peptide and insulin levels had decreased. The infant was positive for anti-insulin and antiglutamic acid decarboxylase antibodies. Immediately after the infant's admission, fluid therapy and intravenous insulin infusion therapy were started. On the second day of the infant's hospitalization and after fluid therapy, he recovered from his lethargic condition, and his general condition improved. Feeding was started on the third day, and he was fed a formula 5 to 7 times a day and ate rice, vegetables, and lean meat. Due to the frequent feeding, the frequency of rapid-acting insulin injection was increased from 3 times before feeding to 5 times, adjusted according to the feeding frequency. The total dose of insulin that was injected was 0.8-1.1 IU/kg/day, and the infant was discharged on the 12th day of his hospitalization. The case is presented herein with a brief review of the relevant literature.
Antibodies ; C-Peptide ; Child ; Diabetes Mellitus, Type 1* ; Diabetic Ketoacidosis* ; Fasting ; Fluid Therapy ; Glucose ; Hemoglobin A, Glycosylated ; Hospitalization ; Humans ; Hydrogen-Ion Concentration ; Incidence ; Infant* ; Insulin* ; Insulin, Short-Acting ; Ketosis ; Male ; Meat ; Urinalysis ; Vegetables

BACKGROUND: Diabetes mellitus (DM) is a major cause of morbidity and mortality in the Philippines. Improvement in hemoglobin A1c (HbA1c) remains below recommended targets for Filipino patients. Safe and effective therapies are needed for this population.
OBJECTIVE: To investigate treatment-emergent adverse events (TEAEs) and change in HbA1c among Filipino patients with DM treated with insulin lispro mix 25/75 in a real-world setting.
MATERIALS AND METHODS: This was a prospective, non-interventional, post-marketing surveillance study among 459 Filipinos aged 18 years or older with type 1 or 2 DM. Patients were treated with insulin lispro mix 25/75 according to the approved label, as prescribed by the investigators, and observed for 12 weeks. Occurrence of all TEAEs and change in HbA1c from baseline to final visit were reported.
RESULTS: Mean (SD) treatment duration was 12.93 (5.7) weeks, and mean total daily dose was 0.62 (0.29) units/kg. Eighteen patients (3.9%) experienced 23 TEAEs, the majority of which were mild. None were reported to be related to treatment. No serious TEAEs or hypoglycemic episodes were reported. Mean (95% confidence interval) HbA1c was significantly reduced by -2.03% (-2.19%, -1.87%), and 36.3% of patients achieved HbA1c <7.0% at 12 weeks.
CONCLUSION: In this observational study, no treatmentrelated safety signals using insulin lispro mix 25/75 were detected among Filipino diabetic patients. HbA1c was significantly reduced in Filipino patients with DM at 12 weeks.

Human ; Male ; Female ; Middle Aged ; Adult ; Insulin Lispro ; Hemoglobin A, Glycosylated ; Hypoglycemia ; Diabetes Mellitus ; Hypoglycemic Agents