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GNRS 5634
Module 2: PICO
Effects of long-acting insulin vs rapid-acting insulin on HgA1c levels in type 2 diabetics
Presented to
Vicky A. Ebone, MSN, RN, GNP-BC
By
Traci Braden
On
December 1st, 2015
THE UNIVERSITY OF TEXAS MEDICAL BRANCH AT GALVESTON
SCHOOL OF NURSING

Introduction
In todays modern world, new technology and medications are constantly changing the
different ways a provider can care for their patients. It is the responsibility of the provider to stay
up-to-date with the most recent evidenced-based practices. The first step in researching a subject
is to formulate a clear and answerable question. The acronym PICO helps the researcher
formulate a question that clearly defines the population of interest (Population), the type of
interventions being tested (Intervention), the types of groups that will be compared (Comparison
groups) and the measurable effect of the intervention (Outcome) (Hastings & Fisher, 2014). The
purpose of this paper is to formulate a PICO question and review the literature to answer that
question.
Background
Clinical Situation. Before a PICO question is formulated, there is typically a life
experience that causes uncertainty and stimulates the researcher to formulate a question. The
clinical experience that helped generate my PICO question happened during my clinical rotation
at a family practice clinic. It was one of my first days at the clinic and I noticed that many of the
diabetic patients were on long-acting insulins, like Levemir or Lantus, alone. This was surprising
to me since my past experiences as a nurse on a med-surg floor were that diabetics were typically
on regular or rapid-acting insulin three times a day without long-acting insulin. I concluded that
the different environment between a med-surg and family practice clinic may have led to the
variance in treatment methods. However, this situation left me wondering which method
controlled blood sugars better - using short-acting insulin three times a day or using long-acting
insulin once a day.

Literature Review. Diabetes is a growing problem in our nation. This disease affects
approximately 129.1 million Americans or 9.3 percent of the population and is the seventhleading cause of death (American Diabetes Association, 2013). It is estimated that type 2
diabetes cost $245 billion in 2012. That cost is even higher when adding in the money spent on
complications from type 2 diabetes, including foot complications such as neuropathy, DKA,
kidney disease, hypertension, and stroke (American Diabetes Association, 2013). An HgA1c
level is a blood tests that calculates a patients blood sugar over three months and is a very
accurate marker of how well a patient is controlling their diabetes. Moran & Burson (2015) state
that studies have shown that lowering HgA1c to seven percent or below reduces microvascular
complications of diabetes and is associated with long-term reduction in macrovascular disease.
With the prevalence of diabetes, along with its high cost and wide array of complications, it is
important to find the most effective diabetic treatment that lowers a patients HgA1c to less than
seven percent or as close as possible.
PICO question and objective
After reviewing the literature on diabetes, I formulated this PICO question that would
guide the research. In non-pregnant type 2 diabetic adults ages 18 or older, are hemoglobin A1c
(HgA1c) levels controlled better with once daily injections that use long-acting insulin, such as
Lantus, or with daily multi-injections that use rapid-acting insulin, such as Lispro or aspart. This
question identifies the population as non-pregnant, type 2 diabetic adults ages 18 and up. The
intervention being studied is insulin therapy specifically rapid-acting and long-acting insulins.
The comparison groups will be patients that use rapid-acting insulin multiple times a day vs.
patients that use long-acting insulin once daily. Finally, we will measure the different
interventions efficacy by looking at the HgA1c levels.

As an adult and geriatric nurse practitioner, I will unavoidably be treating patients with
diabetes. Not only do I intend to learn the efficacy of rapid-acting insulin vs. long-acting insulin,
but I hope the research will expand to show me the best way to manage the care for newly
diagnosed diabetics and those whose blood sugars are not controlled on oral diabetic medications
alone. I also hope to find out which therapies pose the lowest risk for hypoglycemia.
Research
Methods In order to find appropriate evidence to answer the PICO question, extensive
research was conducted. We researched material from up-to-date, from Summon Search, and
PubMed which were all found on the UTMB library website. Google was also used with
attention to only pick scholarly works. Key words searched include glycemic efficacy, insulin
therapies, insulin efficacy, blood sugar testing, diabetes prevalence, diabetic complications, and
diabetes economic costs. Three main articles were found and used to answer the PICO question.
Article 1. A study by Bretzel, Nuber, Landgraf, Owens, Bradley & Linn (2010) looked
specifically at the effectiveness of insulin glargine once daily vs. insulin Lispro three times daily
with meals. The study looked at male and female type 2 diabetic patients aged 18-75 years. All of
the patients had HgA1c levels between 7.5 percent and 10.5 percent and were on oral diabetic
medications. The 418 patients were randomly placed in either the insulin glargine group taken
once or the insulin Lispro group three times daily before breakfast, lunch and dinner. Insulin was
titrated every week in both groups until blood sugar goals were reached. After 44 weeks, the
decrease in HgA1c levels were similar and neither were considered significantly superior to the
other. While there were no significant differences in HgA1c levels between the two groups, the
study did show that patients in the insulin glargine group had a lower incidence of hypoglycemic
episodes and were generally more satisfied with the treatment regimen.

Article 2. A second study by Raz et al. (2011), looked at HgA1c levels in diabetic
patients on insulin Lispro and patients on insulin glargine. However, it differed from the first
article in that it focused more on the different types of insulin and their effects on cardiovascular
risk factors in patients with acute myocardial infarctions. In this study 1,115 patients were
randomly assigned to either the prandial group which used insulin Lispro thrice daily with meals
or the basal group which used insulin glargine once daily. The study found that HgA1c levels did
not differ significantly between the two groups. The study also found that neither group saw a
significant difference in the reduction of cardiovascular risk factors or a difference in the rate of
hypoglycemia episodes.
Article 3. A final article by Holman, Farmer, Davies, Levy, Darbyshire, Keenan & Paul
(2010) looked also at HgA1c levels in patients on insulin aspart administered three times daily
with meals and insulin detemir administered once daily. However, the study added a third
comparison group; insulin NPH a biphasic insulin therapy given twice daily with meals. The
study also looked at weight changes and rate of hypoglycemic episodes. The study consisted of
708 type 2 diabetic adults. Each adult was required to have been diagnosed with diabetes for at
least 12 months and current oral anti-diabetic agents were failing. The patients were randomly
assigned to the biphasic/NPH insulin group, the thrice daily prandial/aspart insulin group or the
once daily insulin glargine group. After 3 years, all three groups saw a reduction in HgA1c levels
but none of the values differed significantly. Weight gain was seen in all 3 groups but a greater
significant weight increase was seen in the prandial and biphasic groups than in the basal.
Finally, the study found that the prandial group had the most amount of hypoglycemic episodes
while the basal group had the least.

Discussion
Once relevant articles are found, the next step in research is to evaluate the evidence in
each article to determine whether the article is of value. Evidence from each article is placed
into a level category and the highest level of evidence articles are used to answer the PICO
question. Different organizations have different levels of criteria and different hierarchy of
levels. According to Hastings, C. & Fisher, C. (2014), the NHMRC evidence hierarchy contains
six levels that evidence can fall into. The NHMRC also recognizes five different types of
research each with different level criteria. These include intervention, diagnostic accuracy,
prognosis, aetiology, and screening intervention. Since our PICO question specifically deals with
the efficacy of an intervention, we will focus on those levels and their criteria.
Level I includes evidence from a systematic review of relevant randomized controlled
trials (RCT). Level II is evidence obtained from at least one well-designed RCT. Level III(a)
includes evidence from a well-designed study but does not have randomization. Level III(b) is
evidence from at least one other type of well-designed quasi-experimental study. The next level,
Level III(c) is evidence obtained from well-designed non-experimental descriptive studies
(comparative studies, correlation studies and case studies). The final level, level IV is evidence
obtained from expert reports/opinions or clinical experience from respected authorities
(Hastings, C. & Fisher, C. 2014).
Article 1. The first study, by Bretzel et al. (2010), is an example of level II evidence. This
article contained evidence from a well-designed randomized control trial. The following qualities
of the article support that this study was a well-designed randomized control trial. The authors
did not declare any bias or conflicts of interest. The study had specific inclusion/exclusion
criteria for selecting participants (for example patients had to be between 18-75 years of age,

have type 2 diabetes for at least one year, and have HgA1c levels between 7.5 and 10.5 percent).
The study used an adequate method of randomization (a central randomization service) and the
two groups had similar HgA1c levels at baseline. There was a sufficient duration to follow-up
(44 weeks). At follow-up greater than 80 percent of participants did indeed follow-up (84.1
percent). Finally, outcomes were assessed objectively with statistical analysis and calculations.
Article 2. The second study, by Raz et al. (2011), is another example of level II evidence.
This article, too, contained evidence from a randomized control trial. The following qualities
from the article help justify that this study was a well-controlled randomized study and thus the
evidence obtained can be classified as level II evidence. This authors did not declare any conflict
of interest or bias. The study had specific inclusion/exclusion criteria for subject selection, which
included patients being between the ages of 30-75 years with type 2 diabetes for at least three
months and patients must have had a myocardial infarction within 21 days of the trial. The
patients were randomly assigned to two different intervention groups. The HgA1c levels, BMI,
and other variables were similar at baseline. In this study, the investigators were blind to which
group the patients were placed in. There was a sufficient duration for follow-up; 1,687 days. The
outcomes were assessed objectively using statistical analysis and calculations. One obstacle that
this study ran into was that it lost more than 20 percent of its participants. This may have been
due to the long length of the study.
Article 3. In the third article, by Holman et al. (2010), we again see level II evidence.
This final article used evidence obtained from a randomized control trial. The authors of this
article declared no bias or conflict of interest. The subject selection had specific inclusion and
exclusion criteria: patients had to be 18 and older with a history of type 2 diabetes for at least 12
months, patients had to have HgA1c levels between 7-10 percent, and had to have been on the

maximum doses of metformin or sulfonylurea for at least 4 months. These patients were
randomly assigned to three different intervention groups. The baseline variables were similar in
all three groups. The patients had a sufficient duration period to follow-up (three years) and
approximately 81.6 percent of patients completed the study. Finally, the outcomes were
statistically analyzed with unbiased calculations. These qualities and others support that this was
a well-designed randomized control study.
Article conclusions. The three articles identified above all contained level II evidence.
With this high level of evidence, we are able to answer our PICO question. Based on the three
articles identified and analyzed we can conclude that there were no significant differences in
HgA1c levels among patients using long-acting insulin once daily and patients using short-acting
insulin thrice daily. We can use this data and generalize it to the diabetic patients we will one day
be taking care of. Since there is no superiority in HgA1c levels, which is the standard measure of
blood sugar control, among the two groups, providers must look at each patient individually and
decide which intervention the patient would benefit most from. Hypoglycemia, weight gain,
nocturnal hypoglycemia, and compliance are just some of the factors providers must keep in
mind. These studies also indicated that if patients fail on one type of insulin therapy, they could
benefit greatly from initiating the second type of insulin therapy concurrently.
Conclusion
The purpose and objective of this paper was to create and answer a PICO question by
using and analyzing significant data. After writing and answering a PICO question about
different insulin therapies and their efficacy with HgA1c levels, I can now take that information
and apply it to my current and future practices. This is a process that all providers should master
to provide the highest quality of care to our patients.

References:
American Diabetes Association (2013). Economic costs of diabetes in the U.S. in 2012. Diabetes
Care, 36, 1033-1046.
Bretzel, R., Nuber, U., Landgraf, W., Owens, D., Bradley, C., & Linn, T. (2010). Once-daily
basal insulin glargine versus thrice-daily prandial insulin lispro in people with type 2
diabetes on oral hypoglycaemic agents (APOLLO): An open randomised controlled trial.
The Lancet, 371, 1073-1084.
Harris C & Garrubba M. Finding the evidence: Guide to the best available evidence to support
introduction of New Technologies & Clinical Practices. 2014. Centre for Clinical
Effectiveness, Monash Health, Melbourne, Australia
Hastings, C., & Fisher, C. (2014). Searching for proof: Creating and using an actionable PICO
question. Nursing Management, 9-12.
Holman, R., Farmer, A., Davies, M., Levy, J., Darbyshire, J., Keenan, J., & Paul, S. (2010).
Three-year efficacy of complex insulin regimens in type 2 diabetes. The New England
Journal of Medicine, 361(18), 1736-1747.
Moran, K. J., & Burson, R. (2015). Blood sugar testing. Home Healthcare Now, 33(2), 103.
Raz, I., Wilson, P., Strojek, K., Kowalska, I., Bozikov, V., Gitt, A., . . . Jacober, S. (2011). Effects
of Prandial Versus Fasting Glycemia on Cardiovascular Outcomes in Type 2 Diabetes:
The HEART2D trial. Diabetes Care, 32(3), 381-386.