Lars Nicklasson

An evaluation of patient preference for an alternative insulin delivery system compared to standard vial and syringe.

ABSTRACT Background: Diabetes mellitus (DM) affects over 18.2 million Americans and diabetes-related medical costs exceed 132 billion dollars per year, totaling more than 12% of the United States healthcare budget. The Diabetes Control and Complications Clinical Trial demonstrated that intensive insulin therapy and the control of plasma glucose can significantly reduce the incidence of late diabetic complications and delay the progression of existing conditions in type 1 diabetes. Optimal glycemic control often requires intensive insulin therapy to maintain a hemoglobin A1C (A1C) of less than 7% as recommended by the American Diabetes Association. It is estimated that more than half of the approximately 7 million Americans using insulin do so with suboptimal treatment and while administering one or two insulin injections per day. Non-adherence may be a contributing factor in suboptimal treatment. For a variety of reasons, many patients diagnosed with diabetes and treated with insulin are non-adherent. Scope: The primary objective of this study was to evaluate preference for an insulin delivery system comparing a disposable doser (InnoLet) to the standard vial/syringe. In a prospective, randomized, open-label, two-period, crossover study, 260 patients were enrolled (age ≥ 18 years, with type 1 or 2 diabetes, and receiving NPH or regular or 70/30 insulin for at least 6-months). A total of 162 patients completed both treatment arms. Excluded were those unable to read/write English or administer their own injections, pregnant/lactating women, those using antipsychotics, and those with a history of alcohol abuse or cognitive impairment. Patients completed the eight-item Diabetes Fear of Self-Injection Questionnaire at baseline, week 12 and week 24. Items were rated on a 4-point Likert scale (1 = almost never; 4 = almost always) with a maximum fear score of 32. At week 24, patients completed a preference survey. Findings: Of the 162 patients completing both treatment arms, 89 (55.0%) were in the vial/syringe to disposable doser treatment arm, 50% were female and mean age was 60 ± 11 years. Patients in both treatment arms displayed little significant differences in baseline characteristics. Patients reported significantly lower fear of self-injection after using the disposable doser compared to vial/syringe (mean ± SEM: 9.5 ± 0.2 vs. 11.2 ± 0.4; p < 0.0001). Most patients (71.5%) indicated a preference for the disposable doser compared to the vial/syringe method ( p < 0.0001). Conclusion: The majority of patients preferred the disposable doser, and reported significantly less fear of self-injection using this delivery system. There are some potential limitations to consider. A randomization bias may have been present, patients who enrolled in this study were those who were actively seeking medical treatment for diabetes, insulin pens and cartridges are not available for all types of insulin regimens, pre-filled pens and cartridges may not be altered and, in general, alternative insulin delivery systems tend to be more costly than insulin sold in traditional vials. However, insulin may have greater patient acceptance and less psychological distress when administered via an alternative delivery system.

Needlestick injury in acute care nurses caring for patients with diabetes mellitus: a retrospective study

ABSTRACT Objective: To quantify the incidence and assess the risk of needlestick injury (NI) in nurses caring for patients with diabetes mellitus. Methods: A total of 400 nurses caring for patients with diabetes in 381 different hospitals throughout the United States over a period of at least 1 year voluntarily completed an Internet-based data collection instrument. The nurses self-reported comprehensive data on their experience with NI, focusing on those occurring within the past year. If respondents experienced multiple NI during this period, detailed data were collected on the most recent event. Results: Of the 400 nurses, 313 (78.3%) reported experiencing at least one NI, 110 (27.5%) reported at least one NI within the last 12 months, and 44 (40% of 110) reported multiple NI. Nearly two-thirds of these injuries (n = 73/110; 66.4%) were punctures that drew blood, resulting in one case of contracted hepatitis C. The cumulative annual incidence of NI events was 448 NI per 1000 nurses. Nurses reported the injury in adherence with existing regulations and policies in only 21.8% of the cases. Disposable syringes were involved in 88 (80%) of the NI events. In half of the injuries (n = 55), the needled device was equipped with a safety feature that was ineffective, primarily because it was not fully activated (n = 47/55; 85.5%) or it malfunctioned (n = 2–5; 3.6–9.1%). NI most commonly occurred while nurses were injecting insulin (n = 33; 30%). In the 2 weeks following their NI, 60.1% of nurses noted that they were more afraid of needled devices than before the injury and 41.8% felt anxious, depressed, or stressed. As a direct result of the NI, nurses missed 77 days of work. Conclusions: This study is the first to show the relatively high risk both of NI and of NI that draws blood among nurses injecting insulin with a disposable syringe and confirms previous incidence estimates of NI among nurses. Additionally, this study reveals significant post-NI emotional distress, suggests significant under-reporting of NI to hospital officials, and demonstrates the need for a more effective needle safety device.

Improving life expectancy and decreasing the incidence of complications associated with type 2 diabetes: a modelling study of HbA1c targets.

To project the long‐term clinical and cost outcomes that accompany predefined improvements in glycaemic control in patients with type 2 diabetes. A peer‐reviewed, validated, non‐product‐specific Markov model of type 2 diabetes was used to project the long‐term clinical and cost outcomes associated with three HbA1c reduction scenarios (vs. no reduction): (i) decreasing mean HbA1c from 9.5% to 8.0%; (ii) from 8.0% to 7.0%; and (iii) from 7.0% to 6.5%. A typical baseline US type 2 diabetes cohort derived from National Health and Nutrition Examination Survey data was simulated over a lifetime horizon (35 years). Incidence of diabetes‐related complications and costs (2005 USD) were accounted based on published data. Discount rates (3% per annum) were applied to clinical benefits and costs. Sensitivity analyses were performed. Stepwise reductions in HbA1c as an independent variable correlated with delayed time to diabetes‐related complications and a reduced cumulative incidence of complications, including cardiovascular, renal and neurologic comorbidities. Related costs also decreased. Reductions in both poorly‐ (9.5–8.0%) and better‐controlled (7.0–6.5%) patients produced incremental gains in undiscounted life expectancy (LE) [1.06 (0.31) and 0.32 (0.34) years [mean (SD)], respectively]. Similar improvement patterns were observed in quality‐adjusted life expectancy (QALE). Benefits from sequential reduction scenarios, when aggregated, exhibited the most dramatic effect. Improved glycaemic control was associated with reductions in complication rates and costs, as well as increased LE and QALE among type 2 patients. These data illustrate the long‐term importance of reaching normoglycaemia and support intensified HbA1c control as a cornerstone of effective long‐term type 2 diabetes management.

Insulin therapy in type 2 diabetes patients failing oral agents: cost-effectiveness of biphasic insulin aspart 70/30 vs. insulin glargine in the US.

Objectives:  To project the long‐term clinical and economic outcomes of treatment with biphasic insulin aspart 30 (BIAsp 70/30, 30% soluble and 70% protaminated insulin aspart) vs. insulin glargine in insulin‐naïve type 2 diabetes patients failing to achieve glycemic control with oral antidiabetic agents alone (OADs).

Long-term clinical and cost outcomes of treatment with biphasic insulin aspart 30/70 versus insulin glargine in insulin naïve type 2 diabetes patients: cost-effectiveness analysis in the UK setting.

OBJECTIVES To evaluate the long-term clinical and cost outcomes associated with biphasic insulin aspart 30/70 (BIAsp 30/70, premixed 30% soluble and 70% protaminated insulin aspart in one injection) compared to insulin glargine treatment in insulin-naïve type 2 diabetes patients failing oral antidiabetic agents in the UK, based on findings recently reported from the INITIATE clinical trial. METHODS The CORE Diabetes Model, a published, peer-reviewed and validated model of diabetes, was used to evaluate life expectancy, quality-adjusted life expectancy, cumulative incidence of complications and direct medical costs over patient lifetimes. The model simulates the range of diabetic complications and disease progression within a series of sub-models (cardiovascular disease, neuropathy, renal and eye disease) based on published data. Baseline cohort characteristics (54.5% male, mean age 52.45 years, mean diabetes duration 9 years, mean HbA(1c) 9.77%) and treatment effects were based on INITIATE. Costs were derived from published UK sources. The analysis was run over a 35-year time horizon (patient lifetime) from a third party payer perspective. Costs and clinical benefits were discounted at 3.5% per annum. Sensitivity analyses were performed. RESULTS BIAsp 30/70 was associated with projected improvements in discounted life expectancy (0.19 +/- 0.20 years) and quality-adjusted life expectancy (0.19 +/- 0.14 quality-adjusted life years [QALYs]), as well as a reduced incidence of retinopathy and nephropathy complications, versus glargine. Total lifetime direct costs were 1319 pounds higher with BIAsp 30/70 than with glargine leading to an incremental cost-effectiveness ratio of 6951 pounds per QALY gained. CONCLUSIONS This study is the first to address the long-term health economic implications of treating type 2 diabetes patients failing oral anti-diabetics with a biphasic insulin mix versus long-acting insulin. Our projections indicate that improved HbA1c levels with BIAsp 30/70 treatment are associated with improvements in life expectancy and quality-adjusted life expectancy, and that BIAsp 30/70 represents excellent value for money compared to insulin glargine in the UK.

Comparing the Long-term Cost-effectiveness of Repaglinide Plus Metformin Versus Nateglinide Plus Metformin in Type 2 Diabetes Patients with Inadequate Glycaemic Control: An Application of the CORE Diabetes Model in Type 2 Diabetes

SUMMARY Objectives: As an example application of the CORE Diabetes Model in type 2 diabetes, we simulated the cost-effectiveness of repaglinide/metformin combination therapy versus nateglinide/metformin for treatment of individuals with type 2 diabetes with an inadequate response to sulphonylurea, metformin, or fixed dose glyburide/metformin. Methods: The CORE Diabetes Model was used to simulate long-term outcomes for a cohort of individuals with type 2 diabetes treated with either repaglinide/metformin or nateglinide/metformin. HbA1c changes for each regimen were taken from a comparative study. At the end of the study, changes in HbA1c from baseline were –1.28% points and –0.67% points for repaglinide/ metformin and nateglinide/metformin, respectively. Median final doses were 5.0 mg/day for repaglinide, 360 mg/day for nateglinide and 2000 mg/day metformin in each treatment arm. Costs were calculated as the annual costs for drugs plus costs of complications (US Medicare perspective) over a 30-year period. Life expectancy (LE) and quality-adjusted life expectancy (QALE) were calculated. Outcomes and costs were discounted at 3% annually. Results: With repaglinide/metformin, improved glycaemic control led to projected decreases in complication rates, improvement of LE and QALE by 0.15 and 0.14 years respectively, and total cost savings of

Deleterious effects of increased body weight associated with intensive insulin therapy for type 1 diabetes: increased blood pressure and worsened lipid profile partially negate improvements in life expectancy.

3,662/person over the 30-year period. Repaglinide/metformin had a 96% probability that the incremental costs per quality-adjusted life year gained would be

Short-term economic impact associated with occupational needlestick injuries among acute care nurses

20,000 or less, and a 66% probability that repaglinide/metformin would be cost-saving compared to nateglinide/metformin. Sensitivity analyses supported the validity and reliability of the results. Conclusions: In the health economic context, repaglinide/metformin combination was dominant to nateglinide/metformin. The CORE Diabetes Model is a tool to help third-party reimbursement payers identify treatments for type 2 diabetes that are good value for money.

Cost-Effectiveness of Diabetes Case Management for Low-Income Populations

SUMMARY Objective: Weight gain is an unwanted side effect of improved glycaemic control in type 1 diabetes, associated with increased blood pressure (BP) and worsening lipid profiles. While improved glycaemic control per se should improve long-term patient outcomes, increases in BP and worsening lipid profiles may counteract these benefits. The aim of this modelling study was to assess whether the increased body weight and associated worsening of lipid profile and blood pressure would negate the improvements in glycaemic control seen with intensive therapy in patients with type 1 diabetes. Methods: A validated diabetes model projected life expectancy (LE), quality-adjusted LE (QALE) and total lifetime costs of complications in type 1 diabetes cohorts with the characteristics of patients from the Diabetes Control and Complications Trial (DCCT). The following four cohorts (A–D) were created based on increased body weight under either conventional or intensive therapy: A) conventional glycaemic control in the subgroup with lowest weight-gain quartile after 6.5 years (HbA1c increased by 11% from baseline); B) conventional control in the highest weight-gain quartile (no change in HbA1c from baseline); C) intensive control in the lowest quartile of weight gain (with 16.1% decrease in HbA1c, but no increase in weight or associated BP, and improved lipid profile); D) intensive control in the highest quartile of weight gain (with 21% decrease in HbA1c, increased systolic BP of 6 mmHg, and worsened lipid profile). Data were derived from DCCT and other published sources. Results: Intensive control, even with weight gain, led to major improvements in LE and QALE, and reduction in costs of complications versus conventional therapy. Intensive therapy with no weight increase led to a higher LE (increased by 0.57 years) and higher QALE (increased by 0.28 years) and lower costs of complications (reduced by

Preference and resource utilization in elderly patients: InnoLet® versus vial/syringe

523/patient), compared to intensive therapy with the highest quartile of weight gain. Conclusions: Concerns about weight gain should not deter intensive insulin therapy. However, the value of improving glycaemic control without increasing body weight (and associated increased BP and worsening of lipid profile) has been confirmed.