BACKGROUND: We aimed to investigate the effectiveness and safety of adding basal insulin to initiating dipeptidyl peptidase-4 (DPP-4) inhibitor and metformin and/or sulfonylurea (SU) in achieving the target glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). METHODS: This was a single-arm, multicenter, 24-week, open-label, phase 4 study in patients with inadequately controlled (HbA1c ≥7.5%) T2DM despite the use of DPP-4 inhibitor and metformin. A total of 108 patients received insulin glargine while continuing oral antidiabetic drugs (OADs). The primary efficacy endpoint was the percentage of subjects achieving HbA1c ≤7.0%. Other glycemic profiles were also evaluated, and the safety endpoints were adverse events (AEs) and hypoglycemia. RESULTS: The median HbA1c at baseline (8.9%; range, 7.5% to 11.1%) decreased to 7.6% (5.5% to 11.7%) at 24 weeks. Overall, 31.7% subjects (n=33) achieved the target HbA1c level of ≤7.0%. The mean differences in body weight and fasting plasma glucose were 1.2±3.4 kg and 56.0±49.8 mg/dL, respectively. Hypoglycemia was reported in 36 subjects (33.3%, 112 episodes), all of which were fully recovered. There was no serious AE attributed to insulin glargine. Body weight change was significantly different between SU users and nonusers (1.5±2.5 kg vs. −0.9±6.0 kg, P=0.011). CONCLUSION: The combination add-on therapy of insulin glargine, on metformin and DPP-4 inhibitors with or without SU was safe and efficient in reducing HbA1c levels and thus, is a preferable option in managing T2DM patients exhibiting dysglycemia despite the use of OADs.
Blood Glucose ; Body Weight ; Body Weight Changes ; Diabetes Mellitus, Type 2 ; Fasting ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Hypoglycemic Agents ; Insulin Glargine ; Insulin ; Metformin ; Morinda

Background: The high prevalence of type 2 diabetes mellitus (T2DM) in the Philippines has burdened the health care system. Therefore, we compared the standard of care Insulin 30/70 + Insulin Glulisine (Arm B) to a traditional insulin regimen NPH Insulin + Regular Insulin (Arm A) to test the concept that both insulin regimens provide comparable effectiveness and safety in real-world practice. Methods : This is a ‘proof-of-concept,’ prospective, randomized, open label pragmatic study of 40 consecutive Filipino T2DM patients from October 2015 to June 2016. The primary endpoint was a reduction in HbA1c at 12 weeks. The secondary endpoints were changes in Fasting Plasma Glucose (FPG), Post Prandial Glucose (PPG), Capillary Blood Sugar (CBS), weight and insulin dose at 12 weeks. ANCOVA and Fisher’s exact tests were used. Results : Patients in treatment arm A showed comparable glycemic control to arm B as measured by reductions in HbA1c (2.89% vs. 2.67%; P = 0.657), FPG (65.94 vs. 46.71 mg/dl; P = 0.57), PPG (76.49 vs. 86.96 mg/dl; P = 0.271) and CBS (115.15 vs. 145.95 mg/dl; P = 0.420). Both treatment arms reported similar weight gain (1.92 vs. 1.22 kg), experienced similar incidence of hypoglycemia (7 vs. 6 patients) and adverse events (AE) (8 vs. 8 patients). Conclusion The traditional combination of NPH Insulin + Regular Insulin offers comparable glycemic control and tolerance as the standard of care without any new safety signals in the Filipino T2DM population. With a lower price, it can be one of the strategies to reduce the fi nancial burden of antidiabetic treatment.
Insulin, Isophane ; Insulin ; Diabetes Mellitus, Type 2

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

BACKGROUND: Many Muslim type 2 diabetes mellitus (T2DM) patients choose to fast the month of Ramadan despite the possible adverse health effects brought about by the change in dietary habits, among other things. Clinical data regarding the safety of multi-drug regimens during fasting are particularly scarce. The aim of the study was to evaluate the safety of a drug protocol devised by the authors to accommodate Ramadan's dietary changes, involving dose adjustments of four anti-diabetic drug regimens in T2DM patients fasting Ramadan. METHODS: In this prospective, observational, open-label study, 301 T2DM patients who wished to fast Ramadan were followed during Ramadan and the preceding month. The incidence of hypoglycemia, diabetic ketoacidosis (DKA) and non-ketotic hyperosmolar state (NKHS) was monitored. Patients were classified into four groups: A group (those taking metformin, sulfonylurea and insulin [n=33]); B group (metformin and sulfonylurea [n=89]); C group (metformin and insulin [n=96]); and D group (premixed 70/30, glargine or regular insulin [n=82]). During Ramadan, drug doses were adjusted as percentages of their pre-Ramadan values: 75% for sulfonylureas, 75% for glargine, 75% for premixed insulin 70/30 in two doses, and 75% for regular insulin. Metformin was adjusted to a twice-daily regimen. RESULTS: No cases of DKA or NKHS were reported. Hypoglycemia occurred at a lower rate than pre-Ramadan values in groups C, and D; and a similar rate in groups A, and B. CONCLUSION: The data suggested that using the above protocol to adjust the doses of anti-diabetic drugs is safe in T2DM patients in regards to hypoglycemia, DKA, and NKHS.
Diabetes Mellitus, Type 2 ; Diabetic Ketoacidosis ; Fasting* ; Food Habits ; Humans ; Hypoglycemia ; Incidence ; Insulin ; Insulin Glargine ; Islam ; Metformin ; Observational Study* ; Prospective Studies

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: The aim of this study was to evaluate the safety and effectiveness of insulin glargine in a large population from a variety of clinical care in Iranian people with type 2 diabetes mellitus (T2DM) and to measure the percentage of patients achieving glycosylated hemoglobin (HbA1c) <7% by the end of 24 weeks of treatment in routine clinical practice. METHODS: This study was a 24 week, observational study of patients with T2DM, for whom the physician had decided to initiate or to switch to insulin glargine. The safety and efficacy of glargine were assessed at baseline and at week 24. RESULTS: Seven hundred and twenty-five people with T2DM (63% female) including both insulin naïve and prior insulin users were recruited in this study. The mean age of the participants was 54.2±11.2 years, and the mean HbA1c level was 8.88%±0.93% at baseline. By the end of the study, 27% of the entire participants reached to HbA1c target of less than 7% and 52% had HbA1c ≤7.5%. No serious adverse event was reported in this study. Furthermore, overall hypoglycemia did not increase in prior insulin users and the entire cohort. In addition, body weight did not change in participants while lipid profile improved significantly. CONCLUSION: Treatment with insulin glargine could improve glycemic control without increasing the risk of hypoglycemic events in people with T2DM. In addition, a significant clinical improvement was observed in lipid profile.
Body Weight ; Cohort Studies ; Consensus* ; Diabetes Mellitus, Type 2* ; Hemoglobin A, Glycosylated ; Humans ; Hypoglycemia ; Insulin Glargine ; Insulin* ; Observational Study

BACKGROUND: There were a limited number of studies about β-cell function after insulin initiation in patients exposed to long durations of sulfonylurea treatment. In this study, we aimed to evaluate the recovery of β-cell function and the efficacy of concurrent sulfonylurea use after the start of long-acting insulin. METHODS: In this randomized controlled study, patients with type 2 diabetes mellitus (T2DM), receiving sulfonylurea for at least 2 years with glycosylated hemoglobin (HbA1c) >7%, were randomly assigned to two groups: sulfonylurea maintenance (SM) and sulfonylurea reduction (SR). Following a 75-g oral glucose tolerance test (OGTT), we administered long-acting basal insulin to the two groups. After a 6-month follow-up, we repeated the OGTT. RESULTS: Among 69 enrolled patients, 57 completed the study and were analyzed: 31 in the SM and 26 in the SR group. At baseline, there was no significant difference except for the longer duration of diabetes and lower triglycerides in the SR group. After 6 months, the HbA1c was similarly reduced in both groups, but there was little difference in the insulin dose. In addition, insulin secretion during OGTT was significantly increased by 20% to 30% in both groups. A significant weight gain was observed in the SM group only. The insulinogenic index was more significantly improved in the SR group. CONCLUSION: Long-acting basal insulin replacement could improve the glycemic status and restore β-cell function in the T2DM patients undergoing sulfonylurea-based treatment, irrespective of the sulfonylurea dose reduction. The dose reduction of the concurrent sulfonylurea might be beneficial with regard to weight grain.
Diabetes Mellitus, Type 2* ; Follow-Up Studies ; Glucose Tolerance Test ; Hemoglobin A, Glycosylated ; Humans ; Insulin* ; Insulin, Long-Acting ; Triglycerides ; Weight Gain

Insulin detemir is a long-acting basal insulin analogue recently introduced in veterinary medicine for treatment of canine diabetes mellitus. As there are only limited studies in dogs, long-term evaluation of insulin detemir in veterinary medicine is required. In this study, we investigated trends in12-hour blood glucose concentration during hospitalization and evaluated initial and following doses of insulin detemir for several months in six diabetic dogs. The mean levels of blood glucose over 12-hour periods were between 113.5 to 327.2 mg/dL, and the average glucose nadir was 103 mg/dL in the six dogs. The dogs were treated with a mean dosage of 0.24 U/kg of insulin detemir, but hypoglycemia was observed in four of the dogs at the first monthly follow-up. Thus, insulin doses were adjusted according to the nadir levels of glucose observed during the follow-up periods (range, 1 to 16 months). The total range of insulin doses throughout the study period was between 0.1 and 0.4 U/kg. Changes in insulin doses in each dog during the follow-up period were not variable. We suggest that insulin detemir might be not only an alternative choice against traditional insulin for patients with insulin resistance or concurrent disease but also an effective home therapy medication in canine patients with DM. This study could help inform veterinary practitioners regarding the use of insulin detemir for canine insulin-dependent DM.
Adrenocortical Hyperfunction ; Animals ; Blood Glucose ; Diabetes Mellitus* ; Diabetic Ketoacidosis ; Dogs* ; Follow-Up Studies ; Glucose ; Hospitalization ; Humans ; Hypoglycemia ; Insulin Resistance ; Insulin* ; Insulin Detemir ; Veterinary Medicine

Insulin plays an important role in the treatment of diabetes. Since it was discovered in the early 1920s, major advances have been made in the medical use of insulin. However, certain insulin associated challenges remain, such as hypoglycemia, weight gain, complex management, and injection site pain. Novel insulins and delivery systems are being developed that can address these limitations. Insulin degludec is a novel basal insulin with a long half-life (25 hours) and action duration (> 42 hours). Glargine U300 is a concentrated formulation of insulin glargine. For improvement in postprandial glucose control, ultrarapid-acting insulins are being investigated. New insulin delivery systems including inhaled insulin and insulin patches are also being developed to overcome the inconvenience associated with subcutaneous injection. In this review, clinical studies of new insulins and new insulin delivery systems are summarized.
Diabetes Mellitus ; Glucose ; Half-Life ; Hypoglycemia ; Injections, Subcutaneous ; Insulin* ; Insulins* ; Weight Gain ; Insulin Glargine

BACKGROUNDThe effectiveness and safety of initiating biphasic insulin aspart 30 in patients who were poorly controlled on oral glucose-lowering drugs were studied in randomized controlled trials, while results from clinical practice remain limited. This subgroup analysis was to provide such findings from a large-scale non-interventional study.

METHODSA1chieve was a multinational, prospective, open-label, non-interventional, 24-week study in patients with type 2 diabetes initiating insulin analogues in 28 countries across Asia, Africa, Europe, and Latin America. After physician had taken the decision to use this insulin, any patient with type 2 diabetes who was not treated with or who had started the study insulin within 4 weeks before inclusion was eligible. Patients were treated with study insulin alone or in combination with oral glucose-lowering drugs. Data on adverse drug reactions, hypoglycemia and glycemic control were collected at baseline, week 12 and 24. This is a report of a Chinese subgroup analysis from the A1chieve study.

RESULTSTotally, 4 100 patients constituted this subgroup. No serious adverse drug reactions were reported. Rates of total, major, nocturnal hypoglycemic events (events/patient per year) were 1.47, 0.10, 0.31 at baseline and 1.35, 0.00, 0.22 at week 24, respectively. Glycemic control was improved as measured by hemoglobin A1c (mean 9.3% to 7.0%, reduction -2.3%), fasting plasma glucose (mean 10.2 to 6.8 mmol/L, reduction -3.5 mmol/L) and postprandial plasma glucose (mean 14.4 to 8.8 mmol/L, reduction -5.6 mmol/L), all P < 0.001. Change in mean body weight was +0.3 kg (P < 0.001).

CONCLUSIONIn this subgroup analysis of the A1chieve study, biphasic insulin aspart 30 improved glycemic control with low risk of hypoglycemia.

Administration, Oral ; Adult ; Aged ; Biphasic Insulins ; administration & dosage ; adverse effects ; therapeutic use ; Blood Glucose ; drug effects ; Diabetes Mellitus, Type 2 ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; metabolism ; Humans ; Hypoglycemic Agents ; therapeutic use ; Insulin Aspart ; administration & dosage ; adverse effects ; therapeutic use ; Insulin, Isophane ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Prospective Studies