Reduced Glucose Variability With Glucose-Dependent Versus Glucose-Independent Therapies Despite Similar Glucose Control and Hypoglycemia Rates in a Randomized, Controlled Study of Older Patients With Type 2 Diabetes Mellitus.

BACKGROUND: Few studies have evaluated continuous glucose monitoring (CGM) in older patients with type 2 diabetes mellitus (T2DM) not using injectable therapy. CGM is useful for investigating hypoglycemia and glycemic variability, which is associated with complications in T2DM. METHODS: A CGM substudy of Individualized treatMent aPproach for oldER patIents in a randomized trial in type 2 diabetes Mellitus (IMPERIUM)) was conducted. Patients were vulnerable (moderately ill and/or frail) older (≥65 years) individuals with suboptimally controlled T2DM. Strategy A comprised glucose-dependent therapies (n = 26) with a nonsulfonylurea oral antihyperglycemic medication (OAM) and a glucagon-like peptide-1 receptor agonist as the first injectable. Strategy B comprised non-glucose-dependent therapies (n = 21) with sulfonylurea as the preferred OAM and insulin glargine as the first injectable. Primary endpoints were duration and percentage of time spent with blood glucose (BG) ≤70 mg/dL over 24 hours at week 24. RESULTS: Duration and percentage of time spent with hypoglycemia at ≤70 mg/dL were similar for Strategy A and Strategy B; glycemic control improved similarly in both arms (LSM change in HbA1c at week 24; A = -1.2%, B = -1.4%). Duration and percentage time spent with euglycemia and hyperglycemia were also similar in both arms. However, Strategy A was associated with lower within-day (21.1 ± 1.2 vs 25.1 ± 1.4, P = .046) and between-day (5.4 ± 1.0 vs 9.1 ± 1.3, P = .038) BG variability (coefficient of variance [LSM ± SE]) at week 24. CONCLUSIONS: This CGM substudy in older patients with T2DM showed lower within- and between-day BG variability with glucose-dependent therapies but similar HbA1c reductions and hypoglycemia duration with glucose-independent strategies.

Glycaemic outcomes of an Individualized treatMent aPproach for oldER vulnerable patIents: A randomized, controlled stUdy in type 2 diabetes Mellitus (IMPERIUM).

AIMS: To compare the glycaemic outcomes of 2 glucose-lowering treatment strategies in vulnerable (moderately ill and/or frail) patients aged ≥65 years with type 2 diabetes whose individual HbA1c targets were not met with diet/exercise and/or oral anti-hyperglycaemic medications (OAMs). METHODS: The primary endpoint of this study was a composite of achieving/maintaining individualized HbA1c targets without "clinically significant" hypoglycaemia (severe hypoglycaemia or repeated hypoglycaemia causing interruption of patients' activities or blood glucose <54 mg/dL). Strategy-A comprised glucose-dependent therapies (n = 99) with a non-sulphonylurea OAM and a glucagon-like peptide-1 receptor agonist as the first injectable. Strategy-B comprised non-glucose-dependent therapies (n = 93) with sulphonylurea as the preferred OAM and insulin glargine as the first injectable. RESULTS: There was no significant difference between Strategy-A and Strategy-B in percentages of patients achieving the primary endpoint (64.5% vs 54.9%; P = .190). Mean incidences (A vs B) of total (10.2% vs 53.8%), documented symptomatic (5.1% vs 36.6%), and asymptomatic (8.2% vs 32.3%) hypoglycaemia were lower for Strategy-A (P < .001 each). Proportions of patients achieving/maintaining HbA1c target (A, 63.3% vs B, 55.9%) were similar. CONCLUSION: Similar proportions of older, vulnerable aged ≥65 years patients with type 2 diabetes achieved/maintained glycaemic treatment goals without clinically significant hypoglycaemia with Strategies A or B. However, Strategy-A resulted in lower risk of total, documented symptomatic, and asymptomatic hypoglycaemia. These results identify an approach of potential clinical benefit in this age group and will inform future clinical research in older patients with type 2 diabetes.

Higher concentration insulins: an overview of clinical considerations.

Three higher concentration insulin products (insulin lispro 200 units/mL, insulin degludec 200 units/mL, and insulin glargine 300 units/mL) received US Food and Drug Administration (FDA) approval in 2015. Although human regular insulin 500 units/mL (U-500) was approved in 1997, a pen and dedicated U-500 syringe became available in 2016. These products offer more treatment options for the increasing numbers of patients requiring insulin to achieve and maintain glycemic targets. Higher concentration insulins have some unique safety and efficacy considerations. Important considerations when transitioning patients from the 100 unit/mL concentration (U-100) to the higher concentration include bioequivalence, pen dose increments, and pen appearance. Bioequivalent insulins have similar pharmacokinetic properties and no dose adjustments are expected when transitioning from the U-100 to the higher concentration. In contrast, higher concentration insulins with different pharmacokinetic and pharmacodynamic properties compared with the U-100 formulation may require dose adjustments. In order to provide safe and effective therapy to patients with higher daily insulin dose requirements, it is important for healthcare professionals to become very familiar with the characteristics of and differences between each of the higher concentration insulins. This paper highlights differences between the U-100 and higher concentration insulins and focuses on practical aspects of use.

Insulin dosing and outcomes among commercially insured patients with type 2 diabetes in the United States.

PURPOSE: The purpose of this study was to examine costs, resource use, adherence, and hypoglycemic events among patients with type 2 diabetes mellitus (T2DM) treated with increasing doses of 100-U/mL (U-100) insulin regimens. METHODS: Data from Truven's Health Analytics Commercial Claims and Encounters database from January 1, 2008, through January 31, 2011, were used. Regressions were used to examine the associations among costs, resource use, adherence, and receipt of a hypoglycemic event and index dose of insulin. Specifically, general linear models with a γ-distribution and log link were used to examine costs, whereas logistic and negative binomial regressions were used to examine resource use and hypoglycemic events. All analyses controlled for patient characteristics, preindex comorbidities, general health, use of antidiabetic medications, and visits to an endocrinologist. FINDINGS: The study focused on 101,728 individuals with T2DM who received an outpatient prescription for U-100 insulin. In general, costs and resource use are highest among patients treated with the highest dose of insulin (>300 U/d). For example, all-cause and diabetes-related hospitalizations and office visits were highest in the highest-dose cohort. Costs generally followed the same pattern. Patients who were prescribed the lowest dose of insulin (10-100 U/d) generally had higher all-cause or diabetes-related inpatient and emergency department costs and resource use compared with those patients with an index dose >100 to 150, >150 to 200, and >200 to 300 U/d. There were generally no significant differences in rates of hypoglycemic events based on index dose. IMPLICATIONS: These results suggest significant differences in patient outcomes based on dosing of insulin. Those patients with T2DM using insulin at the highest and lowest dose ranges have the highest costs and resource use.

Dosing of U-100 insulin and associated outcomes among Medicare enrollees with type 1 or type 2 diabetes.

OBJECTIVE: To examine costs, resource utilization, adherence, and hypoglycemic events among various doses of U-100 insulin regimens among elderly patients (age ≥65 years) diagnosed with diabetes. METHODS: Truven Health Analytics Medicare databases from January 1, 2008 through December 31, 2011 were utilized. General linear models with a gamma distribution and log link were used to examine costs, while logistic and negative binomial regressions were used to examine resource utilization and hypoglycemic events. Analyses controlled for patient characteristics, pre-period comorbidities, general health, and use of antidiabetic medications as well as index dose of insulin. RESULTS: All-cause inpatient, emergency room, and outpatients costs, as well as diabetes-related inpatient costs, were highest among individuals who were treated with an index dose of 10-100 units/day followed by >300 units/day, while drug costs and total costs generally increased as index dosage increased. Resource utilization generally followed the same pattern as costs, with number of office visits increasing as the dose increased and the highest hospital length of stay, number of hospitalizations, number of emergency room visits, and number of diabetes-related hospitalizations were generally highest among those in the lowest and highest index dose cohorts. Compared to patients who initiated with an index dose of 10-100 units/day, all other patients were significantly less likely to achieve an adherence threshold of 80% based upon index dose range, and while those with an index dose of >100-150 units/day were significantly more likely to experience a hypoglycemic event. CONCLUSION: These results suggest that, for elderly individuals with diabetes, there is a higher patient burden among those who receive the lowest and highest insulin doses.