Design and Implementation of an Electronic Tool to Measure Medication Adherence at the Point of Care.

Quality Improvement Success Stories are published by the American Diabetes Association in collaboration with the American College of Physicians and the National Diabetes Education Program. This series is intended to highlight best practices and strategies from programs and clinics that have successfully improved the quality of care for people with diabetes or related conditions. Each article in the series is reviewed and follows a standard format developed by the editors of Clinical Diabetes. The following article describes a project to build a point-of-care tool for assessing patients' adherence to their prescribed medications.

A pragmatic randomized clinical trial of insulin glargine 300 U/mL vs first-generation basal insulin analogues in insulin-naïve adults with type 2 diabetes: 6-month outcomes of the ACHIEVE Control study.

AIMS: To compare the safety and efficacy of insulin glargine 300 U/mL (Gla-300) versus first-generation standard-of-care basal insulin analogues (SOC-BI; insulin glargine 100 U/mL or insulin detemir) at 6 months. METHODS: In the 12-month, open-label, multicentre, randomized, pragmatic ACHIEVE Control trial, insulin-naïve adults with type 2 diabetes (T2D) and glycated haemoglobin (HbA1c) 64 to 97 mmol/mol (8.0%-11.0%) after ≥1 year of treatment with ≥2 diabetes medications were randomized to Gla-300 or SOC-BI. The composite primary endpoint, evaluated at 6 months, was the proportion of participants achieving individualized HbA1c targets per Healthcare Effectiveness Data and Information Set (HEDIS) criteria without documented symptomatic (blood glucose ≤3.9 mmol/L [≤70 mg/dL]) or severe hypoglycaemia at any time of the day at 6 months. RESULTS: Of 1651 and 1653 participants randomized to Gla-300 and SOC-BI, respectively, 31.3% and 27.9% achieved the composite primary endpoint at 6 months (odds ratio [OR] 1.19, 95% confidence interval [CI] 1.01-1.39; P = 0.03 for superiority); 78.4% and 75.3% had no documented symptomatic or severe hypoglycaemia (OR 1.19, 95% CI 1.01-1.41). Changes from baseline to month 6 in HbA1c, fasting plasma glucose, weight, and BI analogue dose were similar between groups. CONCLUSIONS: Among insulin-naïve adults with poorly controlled T2D, Gla-300 was associated with a statistically significantly higher proportion of participants achieving individualized HEDIS HbA1c targets without documented symptomatic or severe hypoglycaemia (vs SOC-BI) in a real-life population managed in a usual-care setting. The ACHIEVE Control study results add value to treatment decisions and options for patients, healthcare providers, payers and decision makers.

Making Inroads in Addressing Population Health in Underserved Communities With Type 2 Diabetes.

IN BRIEF Diabetes continues to represent a substantial individual and societal burden for those affected by the disease and its complications in the United States, and especially for racial/ethnic minorities, the socioeconomically disadvantaged, and the underinsured. Although tools and strategies are now available to manage the condition and its associated comorbidities at the patient level, we continue to struggle to gain control of this health burden at the population health level. Most patients are not achieving desired clinical goals and thus continue to be exposed to preventable risks and complications. As the U.S. health system moves toward a more value-based system of reimbursement, there are opportunities to rethink our approaches to patient and population health management and to harness the available tools and technologies to better understand the disease burden, stratify our patient populations by risk, redirect finite resources to high-impact initiatives, and facilitate better diabetes care management for patients and providers alike.

Hypoglycaemia and treatment patterns among insulin-treated patients with type 2 diabetes who switched to insulin glargine 300 units/mL versus other basal insulin in a real-world setting.

INTRODUCTION: Type 2 diabetes (T2D) is characterized by worsening pancreatic ß-cell function often requiring treatment escalation with oral antidiabetic drugs (OADs), glucagon-like peptide-1 and eventually insulin. Although there is much evidence available on the initiation of basal insulins, fewer studies have investigated the effects of switching from one basal insulin to another. This study aims to evaluate treatment persistence and hypoglycaemia in adult patients with T2D on prior basal insulin who were switched to insulin glargine 300 units/mL (Gla-300) or other basal insulins in a real-world setting. MATERIALS AND METHODS: This study is a retrospective cohort analysis of patient-level data extracted from the Optum® Clinformatics™ database between 1 October 2014 and 30 June 2016. Adult patients (≥18 years) with T2D who were being treated with basal insulin during the 6-month baseline period, who switched to either Gla-300 or other basal insulins, were followed up for ≥3 months after switching. Outcomes included treatment persistence, and incidence and number of hypoglycaemic events. RESULTS: Of the included patients, 1204 switched to Gla-300 and 616 switched to other basal insulins. Adjusting for baseline confounders, patients who switched to Gla-300 were 34% less likely to discontinue their basal insulin than patients who switched to other basal insulins (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.54-0.81; P < 0.001). Patients who switched to Gla-300 were less likely to experience hypoglycaemia at 3-month follow-up (odds ratio [OR] 0.56, 95% CI 0.32-0.97; P = 0.039) and at 6-month follow-up (OR 0.58, 95% CI 0.38-0.87; P = 0.009) compared with patients who switched to other basal insulins. CONCLUSIONS: Patients with T2D on prior basal insulin in a real-world setting who switched to Gla-300 were more persistent with their basal insulin and experienced less hypoglycaemia than patients who switched to other basal insulins.

Clinical Characteristics and Glycemic Outcomes of Patients with Type 2 Diabetes Requiring Maximum Dose Insulin Glargine/Lixisenatide Fixed-Ratio Combination or Insulin Glargine in the LixiLan-L Trial.

INTRODUCTION: iGlarLixi is a titratable, fixed-ratio combination of insulin glargine (iGlar, 100 units/ml) and the glucagon-like peptide-1 receptor agonist lixisenatide for the treatment of patients with type 2 diabetes. This post hoc analysis of the phase 3 LixiLan-L trial (NCT02058160) investigated baseline characteristics, glycemic control, and safety outcomes in participants who received the study-specified maximum dose (60 units/day) of iGlarLixi or iGlar vs. those who received < 60 units/day. METHODS: Outcomes were compared for participants receiving 60 or < 60 units/day at week 30. Endpoints analyzed included change in A1C, fasting plasma glucose (FPG), 2-h postprandial glucose (2-h PPG), body weight, proportion of participants achieving A1C < 7.0%, proportion of participants receiving rescue therapy, documented symptomatic hypoglycemia, and gastrointestinal adverse event (GI AE) incidence. RESULTS: By week 30, 27% (iGlarLixi) and 31% (iGlar) of participants received the maximum dose. Participants on 60 vs. < 60 units/day were younger and had higher body weight, body mass index (BMI), FPG, and baseline insulin dose. In both dose groups, A1C change from baseline was significantly greater with iGlarLixi vs. iGlar, and more participants treated with iGlarLixi vs. iGlar achieved A1C < 7.0%. No significant differences were observed in change from baseline for A1C, FPG, 2-h PPG, or GI AE incidence between insulin dose groups, regardless of treatment. In both treatment arms, incidence of symptomatic hypoglycemia was lower in participants receiving 60 units/day vs. those receiving < 60 units/day. Participants treated with iGlarLixi (< 60 or 60 units/day) had modest weight loss over 30 weeks vs. an increase in weight compared with iGlar. CONCLUSIONS: Maximum doses of iGlarLixi were required in participants with a more insulin-resistant clinical phenotype (younger, higher BMI, FPG, and insulin doses). Benefits were observed with iGlarLixi vs. iGlar, even at 60 units/day, with more participants achieving glycemic goals, no increase in symptomatic hypoglycemia, and a modest reduction in body weight. FUNDING: Sanofi US, Inc.

A randomized trial comparing the efficacy and safety of treating patients with type 2 diabetes and highly elevated HbA1c levels with basal-bolus insulin or a glucagon-like peptide-1 receptor agonist plus basal insulin: The SIMPLE study.

AIM: To compare the efficacy and safety of a glucagon-like peptide-1 receptor agonist (GLP1RA) plus basal insulin versus basal-bolus insulin treatment in patients with very uncontrolled type 2 diabetes. MATERIALS AND METHODS: The SIMPLE study was a 6-month pragmatic, randomized, open-label trial testing the effectiveness of two approaches to treat patients with type 2 diabetes and HbA1c ≥10%. We randomized patients to detemir plus liraglutide or detemir plus aspart (before each meal). The primary endpoint was change in HbA1c; changes in body weight, insulin dose, hypoglycaemia and diabetes-related quality-of-life were secondary outcomes. RESULTS: We randomized 120 participants aged 47.4 ± 9.5 years, Hispanic 40%, African American 42%, diabetes duration 10 [25th-75th percentile (6 to 15)] years, body mass index 37.2 ± 10.3 kg/m2 . HbA1c decreased more with GLP1RA plus basal insulin [12.2% (95% CI 11.8% to 12.6%) to 8.1% (95% CI 7.4% to 8.7%)] compared with basal-bolus insulin [11.8% (95% CI 11.5% to 12.2%) to 8.8% (95% CI 88.1% to 9.55%)]; estimated treatment difference (ETD) of -1.1% (95% CI -2.0% to -0.1%) (non-inferiority margin 0.4% and P = .0001, superiority P = .026). Compared with basal-bolus insulin, treatment with GLP1RA plus basal insulin led to a body weight ETD of -3.7 kg (95% CI -5.8 to -1.5; P = .001), fewer patients experiencing hypoglycaemia [66.1% vs 35.2% (P = .002)], and greater improvements in general/current health perception, treatment satisfaction, and fear of hypoglycaemia, while taking a lower total daily dose of insulin [estimated treatment ratio 0.68 (95% CI 0.55 to 0.84)]. CONCLUSIONS: In patients with HbA1c ≥10% treatment with GLP1RA plus basal insulin, compared with basal-bolus insulin, resulted in better glycaemic control and body weight, lower insulin dosage and hypoglycaemia, and improved quality of life. This treatment strategy is an effective and safe alternative to a basal-bolus insulin regimen.

The Diabetes Unmet Need with Basal Insulin Evaluation (DUNE) study in type 2 diabetes: Achieving HbA1c targets with basal insulin in a real-world setting.

AIMS: To describe in a real-world setting the achievement of physician-selected individualized HbA1c targets in individuals with type 2 diabetes, newly or recently initiated with basal insulin, and the association of hypoglycaemia with target achievement. MATERIALS AND METHODS: A 12-week, prospective, single-arm, observational study of adults with type 2 diabetes, either newly initiated with any basal insulin or start on basal insulin within the preceding 12 months. At enrollment, eligible participants from 28 countries were treated with or without oral antihyperglycaemic drugs and/or GLP-1 receptor agonists. RESULTS: Individualized targets for almost all of the 3139 evaluable participants (99.7%) had been set by their physicians, with 57% of participants having HbA1c targets between 7.0% and <7.5% (53 and <58 mmol/mol). By week 12, 28% and 27% of newly and previously initiated participants, respectively, achieved individualized HbA1c targets with modest average increases in daily insulin dose of 9 and 5 U (0.10 and 0.06 U/kg), respectively, from baseline (14 and 23 U [0.17 and 0.29 U/kg], respectively). Overall, 16% of participants experienced at least one episode of hypoglycaemia. Both the incidence and frequency of hypoglycaemia, but not the severity, were positively associated with a higher likelihood of achieving individualized HbA1c targets (P < 0.05). CONCLUSIONS: In this prospective real-world study, most participants using basal insulin did not achieve the individualized HbA1c targets set by their physicians. Participants who experienced symptomatic hypoglycaemia were more likely to achieve HbA1c targets than those who did not.

Association of Patient Profile with Glycemic Control and Hypoglycemia with Insulin Glargine 300 U/mL in Type 2 Diabetes: A Post Hoc Patient-Level Meta-Analysis.

AIMS: To examine the association of baseline patient characteristics with study outcomes in people with type 2 diabetes receiving insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100), over a 6-month period. METHODS: A post hoc patient-level meta-analysis using data from three multicenter, randomized, open-label, parallel-group, phase 3a studies of similar design, in people previously receiving either basal and prandial insulin, basal insulin + oral antihyperglycemic drugs, or no prior insulin (EDITION 1, 2 and 3, respectively). The endpoints, glycated hemoglobin (HbA1c), hypoglycemia, body weight change, and insulin dose were investigated by subgroups: age (< 65 and ≥ 65 years), body mass index (BMI; < 30 and ≥ 30 kg/m2), age at onset (< 40, 40-50, and > 50 years), and diabetes duration (< 10 and ≥ 10 years). RESULTS: Reduction in HbA1c was comparable between insulins, regardless of subgroup. The lower risk of ≥ 1 nocturnal (00:00-05:59 h) confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemic event with Gla-300 versus Gla-100 was also unaffected by participant characteristics. While heterogeneity of treatment effect between diabetes duration subgroups was seen for the risk of ≥ 1 confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemic event at any time (24 h), treatment effect consistently favored Gla-300; no evidence of heterogeneity was observed for the other subgroups. Annualized rates of confirmed (≤ 3.9 mmol/L [≤ 70 mg/dL]) or severe hypoglycemia and body weight change were not influenced by participant characteristics; a similar pattern was observed with insulin dose. CONCLUSIONS: Comparable glycemic control was observed with Gla-300 versus Gla-100, with less hypoglycemia, regardless of age, BMI, age at onset or diabetes duration. FUNDING: Sanofi. Plain language summary available for this article.

Association of hypoglycaemia severity with clinical, patient-reported and economic outcomes in US patients with type 2 diabetes using basal insulin.

AIMS: To evaluate the clinical and patient-reported outcomes and healthcare utilization and costs associated with patient-reported hypoglycaemia in US adults with type 2 diabetes (T2D) treated with basal insulin. MATERIALS AND METHODS: This was an observational, cross-sectional, survey-based study of adults with T2D on basal insulin ± oral antidiabetes drugs (OADs) or rapid-acting/premixed insulin, who had in the past ever experienced hypoglycaemia, using US data from the National Health and Wellness Survey. Eligible patients were categorized as having no hypoglycaemia (38.7%), non-severe hypoglycaemia (55.1%), or severe hypoglycaemia (6.2%) in the preceding 3 months. Outcomes included health-related quality of life (HRQoL), work productivity and activity impairment, healthcare resource utilization, and estimated direct and indirect costs. Multivariable regression models were performed to control for patient characteristics. RESULTS: Patients who experienced severe hypoglycaemia had significantly (P < .05) lower HRQoL scores, greater overall impairment of work productivity and activity, greater healthcare resource utilization, and higher costs compared with those who experienced non-severe or no hypoglycaemia. Patients with non-severe hypoglycaemia also reported an impact on the number of provider visits, indirect costs, and HRQoL. CONCLUSIONS: Patients with T2D using basal insulin ± OADs or rapid-acting/premixed insulin in the United States who experienced severe hypoglycaemia had greater impairment of activity and work productivity, utilized more healthcare resources, and incurred higher associated costs than those with non-severe or no hypoglycaemia. The study also demonstrated the impact that non-severe hypoglycaemic events have on economic and HRQoL outcomes. Reducing the incidence and severity of hypoglycaemia could lead to clinically meaningful improvements in HRQoL and may result in lower healthcare utilization and associated costs.

Impact of delaying treatment intensification with a glucagon-like peptide-1 receptor agonist in patients with type 2 diabetes uncontrolled on basal insulin: A longitudinal study of a US administrative claims database.

AIM: To evaluate the effect of delaying treatment intensification with a glucagon-like peptide-1 receptor agonist (GLP-1 RA) on clinical and economic outcomes in patients with type 2 diabetes (T2D). METHODS: We conducted a retrospective observational claims study using IMPACT (Impact National Managed Care Benchmark Database) in adult patients with T2D who initiated basal insulin between January 1, 2005 and December 31, 2012, with or without OADs, who remained uncontrolled (glycated haemoglobin [HbA1c] ≥7.0%). Patients were categorized into 3 groups: early, delayed, and no intensification with a GLP-1 RA. We evaluated changes from baseline to follow-up at 12 months for HbA1c level, rate of hypoglycaemic events, and healthcare costs, and we assessed the association between baseline patient characteristics and subsequent treatment intensification. RESULTS: A total of 139 patients (9.0% of 1552 eligible patients) met criteria for inclusion in the early intensification group, 588 patients (37.9%) met criteria for inclusion in the delayed intensification group, and 825 patients (53.2%) met criteria for inclusion in the no intensification group. Mean baseline HbA1c values were 9.16%, 9.07%, and 9.34%, respectively. At follow-up, delayed intensification was associated with significantly smaller decreases in HbA1c from baseline (-0.68%) compared with early intensification (-1.01%). Rates of overall hypoglycaemia were numerically greater in the delayed intensification group than in the early intensification group (0.26 vs 0.06 events/patient-years of exposure, respectively). Change in semi-annual total healthcare costs was greater in the no intensification group (+5266 USD) compared with the early intensification group (-560 USD) and the delayed intensification group (+1943 USD). CONCLUSIONS: Timely addition of a GLP-1 RA to therapy for patients with T2D who were not adequately controlled with basal insulin is associated with better clinical and economic outcomes.

Efficacy and Safety of Insulin Glargine 300 U/mL Versus Insulin Glargine 100 U/mL in High-Risk and Low-Risk Patients with Type 2 Diabetes Stratified Using Common Clinical Performance Measures.

BACKGROUND: To determine whether previously reported reductions in hypoglycemia associated with insulin glargine 300 U/mL (Gla-300) compared with insulin glargine 100 U/mL (Gla-100) are impacted by patient risk category in type 2 diabetes (T2D), clinical performance measures based on the Healthcare Effectiveness Data and Information Set (HEDIS) were applied to patient-level data from the EDITION 2 and EDITION 3 clinical trials that compared Gla-300 and Gla-100. METHODS: In this post hoc analysis, patients were stratified as low risk (LR) if patients were <65 years old with no comorbidities derived from HEDIS (HbA1c target <7.0% [53 mmol/mol]), or as high risk (HR) if patients were either ≥65 years old or had one or more HEDIS-defined comorbidities (HbA1c target <8.0% [64 mmol/mol]). Primary endpoint was a composite of patients achieving HbA1c target without confirmed or severe hypoglycemia over 6 months in the different treatment groups in each of the EDITION trials. RESULTS: There was a statistically nonsignificant trend of more patients treated with Gla-300 achieving the composite endpoint compared with Gla-100 in both the LR and HR patient cohorts, regardless of prior insulin experience. A similar trend was observed for the composite endpoint of HbA1c target without nocturnal hypoglycemia. CONCLUSIONS: There is a consistent, nonsignificant trend suggesting that Gla-300 might reduce the burden of hypoglycemia compared with Gla-100 in patients with T2D irrespective of whether they are classed as LR or HR based on age- and National Committee for Quality Assurance Healthcare Effectiveness Data and Information Set-derived comorbidities.

Achieve control: a pragmatic clinical trial of insulin glargine 300 U/mL versus other basal insulins in insulin-naïve patients with type 2 diabetes.

OBJECTIVE: This study aims to compare the effectiveness of insulin glargine 300 U/mL (Gla-300) with its accompanying patient support program with that of other basal insulin and available patient support programs in patients with type 2 diabetes (T2D) in a real-world setting in terms of achieving HEDIS (Healthcare Effectiveness Data and Information Set) individualized glycemic targets without documented symptomatic hypoglycemia. METHODS: Achieve Control is a US-based, multicenter, randomized, open-label, active-controlled, parallel group pragmatic Phase IV trial in insulin-naïve patients with T2D uncontrolled on ≥2 oral antidiabetes drugs (OAD) and/or glucagon-like peptide-1 receptor antagonists (GLP-1 RA). Inclusion criteria include a diagnosis of T2D, age ≥18 years, and glycated hemoglobin (HbA1c) between 8.0% and 11.0%. Patients will be assigned to either the Gla-300 or other basal insulin group. The primary end point is the proportion of patients achieving HEDIS HbA1c targets (<8.0% [64 mmol/mol] in patients with comorbidities or aged ≥65 years; <7.0% [58 mmol/mol] in all other patients) without occurrence of symptomatic hypoglycemia (blood glucose ≤70 mg/dL) from baseline to 6 months. Secondary end points include rates of documented symptomatic nocturnal hypoglycemia and severe hypoglycemia; change from baseline in HbA1c, fasting glucose, and body weight; treatment persistence; patient-reported outcomes; and healthcare resource utilization. Planned enrollment is 3270 patients across approximately 400 clinical sites. CONCLUSION: Pragmatic clinical trials offer the potential to assess comparative effectiveness in broadly based patient populations receiving care (with or without a corresponding educational support program) in real-world clinical settings. The results of Achieve Control should elucidate the benefits of management of T2D with Gla-300 versus other basal insulins in terms of patient outcomes, experiences, and perceptions, and its impact on healthcare resource utilization and cost. CLINICAL TRIAL REGISTRATION: www.clinicaltrials.gov identifier is NCT02451137.

Insulin stacking versus therapeutic accumulation: understanding the differences.

OBJECTIVE: The build-up in insulin levels following repeated injection of prandial insulin at close intervals--referred to as insulin stacking--can increase the risk of hypoglycemia. With the development of basal insulins with a half-life > 24 hours and a duration of action > 40 hours, clinicians may be concerned about stacking when these long-acting formulations are administered once daily. The objective of this review is to clarify the difference between inappropriate insulin stacking when shorter-acting insulin formulations are repeatedly used to correct hyperglycemia and the appropriate accumulation of long-acting insulin formulations dosed to steady-state pharmacokinetic (PK) profiles. METHODS: Relevant literature on insulin stacking, glucose-clamp studies, and clinical studies of insulin, in conjunction with the clinical experience of the authors, were used to present an overview of insulin PK properties and the effects of appropriate and inappropriate dosing intervals on steady-state conditions and likely clinical outcomes. RESULTS: Clinical studies confirm theoretical PK principles showing that unwanted insulin stacking (excessive concentrations) for basal insulin can be avoided by following recommended dosing and titration algorithms. Long-acting basal insulins need more time to reach steady state than shorter-acting basal insulins but then show reduced peak-trough fluctuations, translating into more consistent biologic action over a 24-hour period. CONCLUSION: The unwanted stacking and consequent hypoglycemia that can occur when correctional doses of rapid-acting insulin are administered at close intervals does not occur when long-acting basal insulins are dosed in appropriate amounts and adjusted at appropriate time intervals (e.g., insulin stacking, insulin administration, diabetes, ultralong duration of action, hypoglycemia every three or more days), allowing for pharmacologic steady-state accumulation.

Intensifying insulin therapy: what options are available to patients with type 2 diabetes?

The progressive nature of type 2 diabetes (T2D) requires practitioners to periodically evaluate patients and intensify therapy when glycemic targets become unattainable with their current treatment regimen. Traditional first- and second-line antidiabetic agents such as metformin and the sulfonylureas do not prevent the characteristic decline in beta-cell function associated with T2D; insulin replacement therapy can therefore quickly become a necessity in some patients. Basal insulin initiation provides an excellent platform to which rapid-acting prandial insulin doses can easily be added, potentially in a stepwise manner, as disease progresses. Premix insulin regimens are another effective intensification option following basal insulin initiation, but are most effective in insulin-naïve patients. The use of insulin in combination with modern T2D agents, such as the incretin-based therapies, has the potential to improve glycemic control while limiting insulin-associated weight gain and hypoglycemia. Further clinical data and approval are required before practitioners can fully endorse this novel approach.

Screening, evaluation and management of depression in people with diabetes in primary care.

Family physicians are responsible for diagnosing and treating the majority of people with type 2 diabetes mellitus and co-morbid depression. As a result of the impact of co-morbid depression on patient self-care and treatment outcomes, screening for depression in the context of a structured approach to case management and patient follow up is recommended in people with diabetes and cardiovascular disease. This review summarizes the need for improved recognition and treatment of depression in diabetes; and makes expert recommendations with regard to integrating screening tools and therapies into a busy family or general medical practice setting.

Effect of baseline glycosylated hemoglobin A1c on glycemic control and diabetes management following initiation of once-daily insulin detemir in real-life clinical practice.

OBJECTIVE: The SOLVE study investigated the initiation of basal insulin in patients with type 2 diabetes on oral antidiabetic (OAD) treatment and outcomes in patients with varying levels of glycemic control at baseline. METHODS: This was an observational cohort study conducted in 10 countries using insulin detemir. Data were collected at 3 clinic visits (baseline, 12-week interim, and 24-week final visit). RESULTS: A total of 13,526 (77.9%) patients were included in the glycosylated hemoglobin A1c (HbA1c) subset analysis. Patients were grouped according to pre-insulin HbA1c values as follows: HbA1c <7.6% (n = 2,797); HbA1c 7.6-9% (n = 5,366), and HbA1c >9% (n = 5,363). A total of 27 patients experienced serious adverse drug reactions (SADRs) and/or severe hypoglycemia (3, 10, and 11 patients with pre-insulin HbA1c <7.6%, 7.6-9.0%, and >9.0%, respectively). All patient subgroups realized improvements in HbA1c, with the pre-insulin HbA1c >9% subgroup having the largest HbA1c reduction (-2.4% versus -0.9% and -0.2% for HbA1c subgroups 7.6-9% and <7.6%, respectively). In the total cohort (n = 17,374), the incidence of severe hypoglycemia decreased from 4 events per 100 person years to <1 event per 100 person years by final visit; the incidence of minor hypoglycemia increased from 1.6 to 1.8 events per person year. CONCLUSIONS: In this study, insulin initiation was delayed until late in disease course, and overall concordance with internationally recognized guidelines was low. The initiation of once-daily insulin detemir was associated with substantial improvements in glycemic control and was not associated with an increase in severe hypoglycemia or weight gain.

Insulin therapy for type 2 diabetes.

Insulin therapy provides effective glycemic control in patients with diabetes who have deficient beta-cell function and insulin secretion. Subjects with type 2 diabetes not adequately controlled on oral agents or incretin therapies can initiate basal insulin replacement to correct fasting hyperglycemia. While all basal insulin preparations have similar efficacy in lowering fasting plasma glucose and improving A1C, the newer basal insulin analogs are associated with a lower risk of hypoglycemia than NPH insulin. Patients whose A1C levels remain above goal despite adequate basal insulin replacement need to evaluate and correct post-prandial hyperglycemia. With progressive beta-cell deficiency, rapid-acting insulin preparations can be introduced before one or more meals and titrated to achieve post-prandial glycemic control. For many patients requiring full basal/bolus insulin replacement, a strategy of fixed prandial insulin doses can yield acceptable glycemic control when compared to a more sophisticated approach utilizing carbohydrate counting and matching to insulin. Concentrated insulin preparations such as U-500 have also been of value in patients with resistant type 2 diabetes. Regardless of the type of insulin replacement used, the blood glucose lowering effects of insulin need to be carefully balanced with the increasing risk of hypoglycemia, and the weight gain associated with insulin intensification.

Insulin degludec: a novel ultra-long-acting basal insulin for use in Type 1 and 2 diabetes.

The prevalence of diabetes, a chronic disease that currently poses a significant health burden in both developed and developing countries, is expected to increase significantly over the foreseeable future. In Type 1 diabetes, insulin replacement is absolutely imperative; in Type 2 diabetes, many patients will eventually require insulin replacement therapy to compensate for progressive ß-cell failure and maintain blood glucose control. Even though currently available insulin analog preparations more closely mimic physiologic insulin needs when compared with neutral protamine Hagedorn insulin, many patients with diabetes still experience unacceptable glycemic control, in part owing to limitations in insulin therapy, such as hypoglycemia risk, weight gain and the need for patients to adjust their lifestyle to their insulin therapy. Insulin degludec, appropriately labeled as an ultra-long-acting basal insulin, promises to achieve similar blood glucose control to currently available preparations (glargine and detemir insulin), with a reduced risk of hypoglycemia and greater flexibility in the day-to-day timing of insulin administration. Greater flexibility in basal insulin administration and/or reducing hypoglycemia risk in insulin-requiring patients with Type 1 or 2 diabetes may facilitate insulin management for patients and physicians.