Insulin Use in Long-Term Care Settings for Patients with Type 2 Diabetes Mellitus: a Systematic

Review Article

Insulin Use in Long-Term Care Settings for Patients with Type 2 Diabetes Mellitus: A Systematic Review of the Literature

Kate Van Brunta, Bradley Curtis, PhDb, Keyla Brooks, PharmDb, Alexandra Heinloth, MDc, Rita de Cassia Castro, MDb,*

aEli Lilly and Company, Windlesham, Surrey, UK

bEli Lilly and Company, Indianapolis, IN

cinVentiv Health Clinical, LLC, Ann Arbor, MI

This systematic review was funded by Eli Lilly and Company.

KVB, BC, and RdCC are full-time employees and stockholders of Eli Lilly and Company. AH is a full-time employee of inVentiv Health Clinical, LLC. Eli Lilly and Company contracted inVentiv Health Clinical, LLC, for writing and editorial services.

*Address correspondence to Rita de Cassia Castro, MD, 900 Ridgebury Road, AOB 3B170, Ridgefield, CT 06877.

E-mail: (R. de Cassia Castro).

Insulin Use in Long-Term Care Settings for Patients with Type 2 Diabetes Mellitus: A Systematic Review of the Literature

Key Words: insulin; nursing homes; geriatrics;

Running title: Insulin use in long-term care settings

Abstract

Objective: To summarize currently available data about insulin therapy in patients with diabetes mellitus (DM), focusing on patients with type 2 diabetes mellitusDM (T2DM), in long -term care (LTC) settings.

Data Sources: Ovid Medline, EMBASE, Cochrane Library databases, and United Kingdom National Health Service (NHS) Economic Evaluation Database, last accessed on November 12, 2012.

Study Eligibility Criteria: We included studies that reported insulin use in patients with T2DM, and studies with combined samples of patients with type 1 DM or T2DM, that were conducted in LTC settings. Excluded were review articles and studies published before 2000.

Results: We identified 11 articles that met all inclusion and exclusion criteria. Insulin use in patients with DM in LTC settings varied widely, from 2.7% to 58.0%. It is difficult to draw conclusions from these proportions, asince many studies did not define whether their populations were exclusively patients with T2DM. Despite recommendations against its use by the American Diabetes Association, the American Geriatrics Society, and the American Medical Directors Association, treatment with sliding-scale insulin (insulin injections adjusted to current blood glucose levels) was very prevalent in the LTC setting. Although the recommended target hemoglobin A1c (A1C) for this patient population varies from ≤6.5% to ≤8.0%, higher A1C values (8.0%–8.9%) were associated with better patient outcomes in a study examining insulin treatment in community-dwelling elderly patients enrolled in an outpatient LTC setting. Insulin pen-devices seemed associated with a high incidence of needle-stick injuries in workers in LTC settings but, compared with insulin vials, showed cost -advantages for use in very short-term (≤30 days) patients with DM in LTC settings.

Limitations: Paucity of available data; only published studies for which full-text articles could be retrieved and which were identified by our search strategy were included; insufficient detail about patient samples were available in many included studies; and potential biases across studies might be introduced by funding sources or study designs.

Conclusions: Available data about insulin therapy in patients with DM in LTC settings are very scarce and great treatment variability of this patient population seems to prevail in the current clinical practice. Additional, randomized, prospective clinical trials are needed to expand our knowledge and allow clinicians to make informed treatment decisions for patients with DM in LTC settings.

Keywords:

Insulin

nursing homes

geriatrics

Introduction

Diabetes mellitus (DM) is prevalent, estimated at 25% to 30% of all patients in long -term care (LTC) settings, according to studies conducted in the United States.1, 2 The LTC setting consists of a variety of services and includes medical and nonmedical care for people who have a chronic illness or disability.3 These LTC services can be provided at home, in the community, in assisted living facilities, or in nursing homes. Several types of LTC facilities exist: home health, independent living, intermediate care, assisted living, skilled nursing, and sub-acute care. There are 2 distinct LTC resident populations: lLong-term stay (more than 100 days)4 residents and short-term stay (less than 100 days) residents. During the first 100 days of a patient’s stay, LTC facilities are financially at risk for the pharmaceutical utilization of residents who are admitted from hospitals. This financial risk is often a driving factor for medication reductions.5 The financial problems of LTC facilities associated with short-term stay residents has have increased in recent years because more admissions to these facilities are coming from acute care facilities discharging very sick patients with extensive medication needs,5 which frequently includinge long periods of intravenous antibiotics.6

Treatment of Type 2 Diabetes Mellitus in the Long-term CareTC Setting

While tThe American Medical Directors Association (AMDA) released target treatment recommendations specifically for the population of elderly patients with type 2 diabetes mellitus (T2DM) in an LTC setting.,1 However, implementing treatment strategies for patients in the LTC setting is often more complex than implementing treatment strategies for the general T2DM population (while acknowledging the need for an individualized treatment approaches for outpatients with T2DM who also face treatment challenges). Patients in LTC settings are likely to have compromised functional and cognitive status along with significant comorbidities that will affect the therapeutic strategy.7 A tailored approach is recommended for LTC patients, with hemoglobin A1c (A1C) goals adapted to each patient based on life expectancy, frailty, presence of comorbidities, cognitive impairment, functional disability, resources, and support system.8, 9 In a Consensus Development Conference on Diabetes and Older Adults in 2012, the American Diabetes Association (ADA) developed the following guideline for A1C goals in this patient population: Ffor Rrelatively healthy patients (few coexisting conditions, intact cognitive and functional status) with a longer remaining life expectancy, an A1C goal of lower than <7.5% is recommended; for more complex patients with an intermediate health status (multiple coexisting conditions or mild to moderate cognitive impairment) the A1C goal should be adjusted to lower than <8.0%; and for very complex patients with poor health status (long-term careLTC or end-stage chronic illnesses or moderate to severe cognitive impairment) and limited remaining life expectancy, an A1C goal of lower than <8.5% can be acceptable.9 Recommended A1C goals range from ≤6.5% (American Association of Clinical Endocrinologists [AACE]) to <7.0% (American Diabetes Association [ADA]) for nonpregnant adults, but both organizations state that less stringent A1C goals may be appropriate in patients with limited life expectancies. Additionally, the ADA recommends the following capillary plasma glucose goals: preprandial 90-130 mg/dL (5.0-7.2 mmol/L); peak postprandial <180 mg/dL (<10.0 mmol/L). Similarly, the AACE recommends fasting plasma glucose levels of <110 mg/dL and 2-hour postprandial plasma glucose levels of <140 mg/dL. The position statement on DM management in older people (not focused on patients in LTC settings) by the International Association of Gerontology and Geriatrics (IAGG), the European Diabetes Working Party for Older People (EDWPOP), and the International Task Force of Experts in Diabetes recommends an A1C target range of 7.0% to 7.5%, which may be adjusted to reduce the risk of hypoglycemia in patients with functional dependence, care home residency, dementia, or those who receive end-of-life care.10

While currentIt is recommended ations for blood glucose monitoring recommend at least three finger-sticks per day, the guidelines also recognize that monitoring should be to individualize blood glucose monitoringd based on patient needs and goals.1 Dietary restrictions for patients in LTC settings generally are not recommended, so that adverse outcomes associated with malnutrition can be avoided.1, 11 Recently published guidelines of the ADA, in conjunction with the American Geriatrics Society (AGS), highlight the importance of monitoring and encouraging fluid intake to diminish the risk of volume depletion and hyperglycemic crises.9 An additional issue in LTC facilities is frequent staff turnover, which leads to unfamiliarity with vulnerable patient management. Implementing evidence-based policies for glycemic control, use of insulin, and treatment of hypoglycemia can alleviate risks caused by frequent staff turnover.9

Given such complexity, it is no surprise that data from several studies suggest that a significant number of residents in LTC settings receive suboptimal diabetes care.12 Reviews of glycemic targets and treatment strategies for T2DM in LTC settings have identified gaps in both the knowledge of treatment strategies and understanding of how providers modify target goals for A1C.13 Noted are the need for future research to improve understanding of “optimal glycemic control” and the best way to implement treatment regimens in these challenging treatment environments.14

Use of Insulin in the Long-term CareTC Setting

While Although recent reviews have examined the use of insulin to treat elderly patients with DM,15 little focus has been given to analyzing the existing evidence on the use of insulin in the LTC setting. Many elderly patients with T2DM require, or will eventually require, insulin to achieve or maintain their glycemic goals.16 However, insulin therapy is often under-ustilized in elderly patients.14

The AMDA recommends a three3-tiered approach to diabetes management in residents of LTC facilities. If possible, metformin therapy should be initiated with lifestyle modification as a first tier.16 If metformin is contraindicated and fasting glucose levels are significantly elevated, initiation of basal insulin should be considered. In medically unstable residents with blood glucose levels that are consistently higher than 180 mg/dL, more intensive insulin regimens may be indicated as first-line therapy. If metformin and lifestyle modifications fail to achieve adequate blood glucose control, use of additional oral agents or initiation of insulin therapy should be the second tier in the approach to diabetes management. Finally, the third tier should be initiation of intensification of insulin therapy if diet, exercise, and oral agents do not achieve adequate blood glucose control or if oral agents are contraindicated.16

Sliding-scale insulin (SSI) treatment is not recommended due tobecause of the retrospective treatment of hyperglycemia (patients receive an insulin injection after an elevated blood glucose value has been determined) and lack of efficacy evidence.1 Despite numerous criticism of the SSI approach, recent research has found the procedure continues to be used.14 The ADA/AGS guidelines discourage the use of SSI alone for chronic glycemic management in LTC facilities.9

While Although AMDA does not recommend prolonged use of SSI, the organization does acknowledge that SSI treatment may be useful in residents of LTC settings newly diagnosed with diabetes or in transition phases when new therapies are initiated.16 However, SSI treatment should be re-evaluated within 1 week of initiation and converted to fixed daily insulin doses.16

Objective of this Review Article

Although many publications examined the use of insulin and the treatment of diabetes in the elderly, little focus has been given to synthesize the existing evidence around the use of insulin in the LTC population specifically. As such, the purpose of this structured review is to summarize the currently available literature about the use of insulin in the treatment of patients with DM, specifically focusing on patients with T2DM in the LTC setting. The intention of this literature review is to inform future research and serve as a foundation for possible study designs.

Methods

This review follows guidelines proposed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Group.17 No review protocol was registered for this study. Included were original articles reporting insulin treatment in elderly LTC residents diagnosed with DM, with a focus on T2DM. To find eligible studies, abstracts were screened and selected from accepted scientific databases based on the following inclusion and exclusion criteria.:

Inclusion Criteria

1.Study involved the use of insulin (mealtime, basal, or other).

2.Study involved sample of patients with T2DM, or diabetes not otherwise specified (assumed to be combined sample of patients with T1DM and T2DM).

3.Study conducted in an LTC setting (subcategories within this setting including skilled nursing, assisted living, sub-acute care, nursing home, nursing care, and home health).

Exclusion Criteria

1.Articles were reviews, case studies, editorials, comments, books, dissertations, opinions papers, and letters. Relevant review articles (Supplemental Table 1)2, 14, 15, 18–-24 were searched for primary references so that empirical data from the primary references could be captured in our review if available.

2.Articles were published before 2000.

Literature was retrieved from Ovid Medline, EMBASE, and Cochrane Library databases, and United Kingdom National Health Service (NHS) Economic Evaluation Database on November 12, 2012, with the following search terms: non insulin dependent diabetes mellitus, insulin, Long term care or Residential Facilities. Titles, abstracts, and keywords were searched for the following exact synonyms: LTC or Long term care or nursing home or residential home, insulin, type 2 diabetes or non insulin dependent diabetes or type 2 diabetes. Detailed search strategies are provided in the Supplemental Text 1.

All retrieved abstracts were initially screened and studies that clearly met the exclusion criteria were excluded by one of the authors (KB). The remaining studies were re-screened by another author (KVB) to ensure residents of LTC facilities diagnosed with DM who received treatment with insulin were included. In cases in which the abstract did not include enough detail, full-text references were retrieved and screened. Only articles meeting the above inclusion/exclusion criteria published from 2000 to present were included. The final list of included studies was determined in discussions among the authors.

From the selected articles, patient characteristics, diabetes treatment regimens, diabetes-related health outcomes, patterns of care, and economics outcomes were retrieved. No assessment of risk of bias in individual studies or across studies was undertaken.

Results

A total of 541 unique potentially relevant articles were retrieved with the search strategies described abovepreviously. Of those, 10 articles were included in the current review. Additionally, one 1 article was identified for inclusion by screening the references of the retrieved review articles (Supplemental Table 1). A total of 530 retrieved references were excluded for the following reasons: reference type— - review, editorial, case study, comment, book, dissertation, opinion, letter (n=44); study not specific to the LTC setting (n=187); study not conducted in patients with diabetes (n=54); study did not involve the use of insulin (n=67); duplicate references (required manual removal, n=2); and published prior tobefore 2000 (n=176) (Figure 1).

Data Extraction

Study outcomes relevant to this review were are summarized in Table 113, 25-–34 for all included articles. However, outcome measures and study designs were very different among studies, which limited our ability to synthesize clear summary results.

Studies Reporting Patient Outcomes

With our search criteria, we identified a total of four 4 publications reporting patient-related outcome measures for insulin therapy in LTC settings (Table 1). In a longitudinal cohort study, elderly patients diagnosed with DM were followed for 2 years.34 Although this study did not clearly specify whether the sample included patients with T1DM, T2DM, or both, it is assumed to be a sample of patients with T1DM or T2DM, with a majority ofmost patients having T2DM, given the relative prevalence of T2DM in elderly populations, and the high proportion of patients in this study reported as taking oral-only regimens. The patients were nursing home eligible but continued to live in community settings while participating in On Lok Lifeways® (On Lok, Inc., San Francisco, CA ), a comprehensive health plan that provides LTC in an outpatient setting. Almost one-third of patients were taking only oral antihyperglycemic medications at baseline, and one-half were taking insulin. While Although it was noted that the patients received medication management by Lok Lifeways, no further details about potential medication self-administration were provided. The investigators grouped the study population by baseline A1C values (<7.0%, 7.0%–7.9%, 8.0%–8.9%, and ≥9.0%) and stratified their analyses by diabetes treatment (any insulin versus oral antihyperglycemic medication only). In patients treated with insulin, higher A1C values (8.0%–8.9%) were associated with better patient outcomes after 2 years of follow-up (lower percentages of death [21% versus 35%] and functional decline [46% versus 51%]) than A1C values of 7.0% to –7.9%. The investigators concluded that a target A1C of ≤8.0% or lower as recommended by the AGS for older adults with limited life expectancy might be lower than necessary to maintain function.34 The ADA generally recommends a target A1C of lower than <7.0% for nonpregnant adults, but qualifies this recommendation with the statement that less stringent A1C goals may be appropriate in patients with limited life expectancies.35 Similarly, the American Association of Clinical EEndocrinologists recommends a target A1C of ≤6.5% or lower for nonpregnant adults but states that less stringent A1C goals (7%–8%) may be considered in patients with limited life expectancy.36 Interestingly, the study by Yau and coworkers34 cited above previously showed the A1C range of 8.0% to –8.9% was associated with the best 2-year patient outcomes.

Based on data from a large sample of patients with T2DM patients living in LTC facilities, two 2 retrospective chart reviews examining details of the patients’ insulin therapy were published. The first report examined the use of SSI in this patient population and concluded that the majority ofmost patients received SSI therapy (alone or supplemental).31 While Although the patients showed good glycemic control (mean [standard deviationSD]: A1C = 7.2% [1.3]; fasting blood glucose = 146.4 [43.6] mg/dL), the investigators questioned the high finger-stick burden necessitated by SSI therapy, with 62.8% of finger-sticks not leading to subsequent insulin administration.32 The second report focused on the use of basal insulin in patients with T2DM in LTC facilities and compared outcomes between patients receiving insulin glargine (IGlar) or insulin detemir (IDet).26 The majority ofMost patients treated with basal insulin received IGlar (942/1142). Patients treated with IGlar had significantly lower A1C levels (7.31% versus 7.72%, P = .02) and fewer urinary infections (9.3% versus 17%, P .01) compared with patients receiving IDet. No significant between-group differences were observed for the frequency of hypoglycemic events or other clinical events.26