Switching from Neutral Protamine Hagedorn (NPH) Insulin to Insulin Glargine 300 U/mL in Older and Younger Patients with Type 2 Diabetes: A Post Hoc Analysis of a Multicenter, Prospective, Observational Study.

INTRODUCTION: Older age and longer disease duration are key risk factors for hypoglycemia in patients with type 2 diabetes (T2D) who receive insulin. Previous studies have shown that insulin glargine 300 U/mL (Gla-300) improves glycemic control and reduces the risk of hypoglycemia, but whether this effect is observed in older patients switching from neutral protamine Hagedorn (NPH) insulin is unclear. METHODS: In this multicenter, observational study involving patients with T2D aged ≥ 18 years with glycated hemoglobin (HbA1c) ≥ 8%, we compared the safety and effectiveness of switching from NPH insulin to Gla-300 in subgroups of patients differing by age (< 65 vs. ≥ 65 years) and duration of diabetes (≤ 13 vs. > 13 years). RESULTS: A total of 469 participants were included in the study. From baseline to 6 months after switching to Gla-300, mean HbA1c decreased from 9.23% to 8.13% (p < 0.001) among patients aged ≤ 65 years (224 patients), and from 9.15% to 8.20% (p < 0.001) among those aged > 65 years (245 patients). The proportion of patients with ≥ 1 episodes of hypoglycemia decreased from 19.1% to 13.6% (p = 0.11) among those aged ≤ 65 years, and from 26.9% to 13.0% (p < 0.001) among those aged > 65 years; the reduction was significantly greater in those aged > 65 years (p = 0.001). The reduction in HbA1c was greater in those with a disease duration ≤ 13 years (p = 0.007), but the reduction in hypoglycemia was greater in those with a disease duration > 13 years (p < 0.0003). CONCLUSION: The switch from NPH insulin to Gla-300 improved glycemic control in older patients with T2D and in those with a longer disease duration. Older patients with T2D and those with a longer disease duration benefited even more from the switch to Gla-300 than younger patients and those with a shorter disease duration, with significantly greater reductions in the risk of hypoglycemia.

Switching from Neutral Protamine Hagedorn Insulin to Insulin Glargine 300 U/mL Improves Glycaemic Control and Reduces Hypoglycaemia Risk: Results of a Multicentre, Prospective, Observational Study.

Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality worldwide and is an important public health issue. A significant proportion of insulin-treated patients with T2DM do not reach target glycated haemoglobin (HbA1c) values, which ultimately increases their risk of long-term microvascular and macrovascular complications. One potential option to improve diabetes control in these patients may be the use of new insulin formulations including second-generation basal insulin analogues such as insulin glargine 300 U/mL (Gla-300). Several published randomised controlled trials have assessed the clinical effectiveness of Gla-300, mostly versus insulin glargine 100 U/mL as well as insulin degludec. However, there is limited information about the real-world effectiveness of Gla-300 when patients are transitioned directly from neutral protamine Hagedorn (NPH) human basal insulin. The primary objective of this study was to evaluate the effectiveness of Gla-300, defined as the percentage of participants with an HbA1c reduction of ≥0.5%, 6 months after switching from NPH insulin, in participants with T2DM. Secondary objectives included the safety assessment based on the percentage of patients experiencing ≥1 episodes and the number of hypoglycaemic episodes by category: severe, symptomatic, symptomatic confirmed, diurnal or nocturnal, change in body weight, and insulin dose. A total of 469 participants completed the 6-month observation period. Mean baseline HbA1c was 9.19%. The percentage of participants with a ≥0.5% improvement in HbA1c from baseline was 71.7% at 6 months. Mean HbA1c decreased at 3 and 6 months by 0.77% (±0.98) and 1.01% (±1.12), respectively (p < 0.00001 versus baseline), while fasting glycaemia decreased by 32 mg/dL and 37 mg/dL, respectively (p < 0.00001 versus baseline). There were moderate increases in the doses of both Gla-300 and, if used, short-acting insulins during the 6 months of observation. The percentage of participants with ≥1 hypoglycaemia event during the preceding 4 weeks decreased significantly from baseline to 3 and 6 months, as did the proportion with symptomatic hypoglycaemia at night (p < 0.00001 versus baseline). No participants had severe hypoglycaemia after a switch to Gla-300. Body mass, waist and hip circumferences, and waist : hip ratio did not change significantly. In conclusion, this large, prospective, observational study demonstrated that switching from NPH insulin to Gla-300 resulted in a significant improvement in HbA1c, with only a moderate increase in insulin dose, a decreased risk of hypoglycaemia, and no increase in body weight.

The phenomenon of HbA1c stability and the risk of hypoglycemia in long-standing type 1 diabetes.

AIMS: Hyperglycemia is the major factor underlying vascular complications of diabetes. Unfortunately, improved glycemia control is frequently accompanied by an increased risk of hypoglycemia. The aim of the study was to assess the relationship between hemoglobin A1c (HbA1c) and 1-week Continuous Glucose Monitoring (CGM) data in long-standing type 1 diabetes (T1DM). METHODS: We recruited 58 subjects with long-standing T1DM consecutively enrolled to the study. Each patient underwent a 1-week CGM and laboratory profile at baseline. Subjects were divided into three subgroups according to baseline HbA1c tertiles: T1 < 7.1%, T2 = 7.1-8.0%, and T3 > 8.0%. RESULTS: T1 patients were characterized by the longest time in range (66% of a week), whereas T3 patients experienced hyperglycemia in >50% time of the week. T1 patients were noted to have 25% of nighttime with glycemia <3.9 mmol/L (8% with glycemia <2.8 mmol/L). Most recent HbA1c closely reflected 10-years mean HbA1c values (R = 0.83; P < 0.0001). CONCLUSIONS: (1) Long-term diabetes control (10 years HbA1c mean) is a strong predictor of the current HbA1c levels. (2) Current and historical HbA1c levels are closely linked to CGM-derived glycemia. (3) Risk of clinically significant hypoglycemia negatively correlates with HbA1c. (4) HbA1c > 8.0% is associated with unsatisfactorily low (44%) time in range.

Intensive glucose therapy and clinical implications of recent data: a consensus statement from the Global Task Force on Glycaemic Control.

BACKGROUND: There is compelling evidence showing that achieving good glycaemic control reduces the risk of microvascular complications in people with type 1 and type 2 diabetes. Likewise, there is clear evidence to show that achieving good glycaemic control reduces the risk of macrovascular complications in type 1 diabetes. The UKPDS 10-year follow up suggests that good glycaemic control also reduces the risk of macrovascular complications in type 2 diabetes. Despite this, recent results from ACCORD, ADVANCE and VADT present conflicting results and data from the ACCORD trial appear to suggest that very low HbA(1c) targets (<6.0%) may, in fact, be dangerous in certain patient populations. AIM: To review recent results from ACCORD, ADVANCE and VADT and provide clear guidance on the clinical significance of the new data and their implications for the practising physician treating patients with type 2 diabetes. METHODS: A Pubmed search was used to identify major randomised clinical trials examining the association between glycaemic control and diabetes-associated complications. The data was reviewed and discussed by the GTF through a consensus meeting. The recommendations for clinical practice in this statement are the conclusions of these analyses and discussions. RESULTS: Evidence from ACCORD, ADVANCE, VADT and UKPDS suggests that certain patient populations, such as those with moderate diabetes duration and/or no pre-existing CVD, may benefit from intensive blood glucose control. These trials highlight the benefit of a multifactorial treatment approach to diabetes. However, ACCORD results indicate that aggressive HbA(1c) targets (<6.0%) may not be beneficial in patients with existing CVD and a longer duration of diabetes. CONCLUSIONS: Glycaemic control remains a very important component of treatment for type 2 diabetes and contrasting results from the ACCORD, ADVANCE and VADT should not discourage physicians from controlling blood glucose levels.