760962

research-article2018
TAE0010.1177/2042018818760962Therapeutic Advances in Endocrinology and MetabolismS. M. Pearson and J. M. Trujillo

Therapeutic Advances in Endocrinology and Metabolism Original Research

Conversion from insulin glargine U-100 to

Ther Adv Endocrinol
Metab

insulin glargine U-300 or insulin degludec

2018, Vol. 9(4) 113­–121

DOI: 10.1177/
https://doi.org/10.1177/2042018818760962
https://doi.org/10.1177/2042018818760962
2042018818760962

and the impact on dosage requirements © The Author(s), 2018.

Reprints and permissions:
http://www.sagepub.co.uk/
journalsPermissions.nav
Scott M. Pearson  and Jennifer M. Trujillo

Abstract
Background: We wanted to determine whether basal insulin requirements change when
patients transition from insulin glargine U-100 (Gla-100) to insulin glargine U-300 (Gla-300) or
insulin degludec.
Methods: This study involved subjects seen in the University of Colorado Health Endocrine
Clinic who were transitioned from Gla-100 to either Gla-300 (n = 95) or insulin degludec (n =
39). The primary outcome was the difference between baseline Gla-100 dose and dose of Gla-
300 or insulin degludec prescribed after first follow-up visit within 1–12 months. Secondary
outcomes included changes in glycemic control and empiric dose conversion from Gla-100
to Gla-300 or insulin degludec on the day of transition. Wilcoxon rank sum tests evaluated
changes in insulin doses, and paired t tests assessed changes in glycemic control using
GraphPad statistical software.
Results: Median daily basal insulin dose increased for individuals transitioned from Gla-100
to Gla-300 from 30 [19–60 interquartile range (IQR)] units at baseline to 34.5 (19–70 IQR) units
after follow up (p = 0.01). For patients transitioned to insulin degludec, dose changes from
baseline to follow up were not significantly different (p = 0.56). At the time of transition, the
prescribed dose of Gla-300 or insulin degludec did not significantly differ from the previous
dose of Gla-100 (p = 0.73 and 0.28, respectively), indicating that empiric dose adjustments
were not routinely prescribed.
Conclusions: Patients who transitioned from Gla-100 to Gla-300 had increased basal insulin
requirements between visits, while basal insulin requirements for those transitioned from
Gla-100 to insulin degludec were not significantly different.

Keywords:  endocrinology, insulin action, insulin therapy, novel agents

Received: 13 November 2017; revised manuscript accepted: 1 February 2018

Correspondence to:
Scott M. Pearson
Introduction slowly over time.2 With an average 3-h onset and University of Colorado
Around 29 million Americans are living with type 20-h duration of action, Gla-100 offers longer Skaggs, School
of Pharmacy and
1 or type 2 diabetes, with an estimated 28% of coverage and a less pronounced peak effect when Pharmaceutical Sciences,
these people using insulin.1 Basal insulin is popu- compared with neutral protamine Hagedorn 12850 East Montview
Boulevard, Mail Stop C238.
lar among prescribers and patients due to its long (NPH) insulin or insulin detemir.2,3 Still, at lower Aurora, CO 80045, USA
duration of action and ease of use. The ideal basal doses of Gla-100, many patients require twice University of Colorado,
12850 East Montview
insulin would have a peakless pharmacokinetic daily dosing to maintain adequate control Boulevard, CO 80045, USA
profile, 24-h duration of action allowing for once- throughout the day, and at higher doses, patients spearson15@gmail.com
Jennifer M. Trujillo
daily injections, and a minimized risk of hypogly- may experience discomfort from injecting large University of Colorado
cemia. Insulin glargine U-100 (Gla-100) is an volumes.4 Therefore, certain subsets of people Skaggs School
of Pharmacy and
acidic solution which forms a precipitate in the may benefit from a basal insulin with a differing Pharmaceutical Sciences,
subcutaneous tissue upon injection and releases pharmacokinetic profile. Aurora, Colorado

journals.sagepub.com/home/tae 113
Therapeutic Advances in Endocrinology and Metabolism 9(4)
The approvals of insulin glargine U-300 (Gla-300)
and insulin degludec in 2015 opened the door to a
new and unique selection of basal insulins.5,6 Gla-
300 is three times more concentrated than Gla-
100, develops its onset over 6 h, and has a duration
of action of 36 h.2 These characteristics are thought
to provide a more even distribution of insulin
throughout the day compared with Gla-100. Gla-
300 has also been shown to be equally safe and
effective when injected 3 h before or after the
scheduled dosing time.7 The Phase III EDITION
trials showed subjects taking Gla-300 to have simi-
lar glycemic control and lower rates of nocturnal
hypoglycemia compared with those taking Gla-
100, although those receiving Gla-300 required
doses 12–18% higher than those receiving Gla-
100.2,8–11 It is postulated that this higher dosing
requirement may be due to a mildly lower bioavail-
ability for Gla-300, perhaps related to a prolonged
residence time in the subcutaneous tissue and sub-
sequent tissue peptidase interactions.12
Insulin degludec is formulated with zinc and
forms a depot composed of multihexamer chains
after being injected into the subcutaneous space.13
As the zinc molecules dissociate, single mono-
mers of insulin degludec are slowly released into
the bloodstream over time. Insulin degludec has
an average 42-h duration of action and provides
steady insulin levels throughout the day.3 Its
pharmacokinetics also allow for more flexible
dosing, with subsequent injections permissible
8–40 h after the previous dose. Insulin degludec is
currently available in U-100 and U-200 formula-
tions. Despite differences in concentration, these
two products exhibit equivalent pharmacokinetic
and pharmacodynamic profiles.14 Insulin deglu-
dec has shown similar glycemic control with lower
rates of nocturnal hypoglycemia compared with
Gla-100.15–18 To achieve these outcomes, the
Phase III BEGIN studies showed that 11–12%
lower doses of insulin degludec were required
compared with Gla-100.
Patients may transition from one basal insulin to
another for many reasons, including their dosing
flexibility and convenience, lower injection vol-
ume, and seemingly lower rates of hypoglycemia.
While the choice of basal insulin should be made
based on factors such as disease and drug charac-
teristics, efficacy, and safety, nonmedical switch-
ing often occurs due to cost, insurance formulary
preferences, and during care setting transitions.19
Although clinical studies found subjects to have
different dose requirements when taking Gla-100
114 journals.sagepub.com/home/tae
as opposed to Gla-300 or insulin degludec, the
package insert for each of these new basal insulin
products recommends switching patients previ-
ously taking Gla-100 by a 1:1 unit dosage conver-
sion.5,6 In addition, current guidelines do not
offer specific recommendations for switching
between basal insulin products.
Despite these recommendations and findings in
the literature, it is unclear what happens in real
world clinical practice when patients are transi-
tioned from one basal insulin to another. If
patients are transitioned to these alternative insu-
lins with a 1:1 unit dosage conversion, they may
experience changes in glycemic control prior to
being seen again in clinic. Therefore, the purpose
of this study was to retrospectively examine a
population of patients with type 1 and type 2 dia-
betes managed in a diabetes specialty clinic, who
were transitioned from Gla-100 to either Gla-300
or insulin degludec and assess their dosage con-
version. Documentation of their first follow-up
visit was also examined to determine whether or
not doses required adjustment and to assess blood
sugar control following this transition. If con-
cluded that dose adjustments were necessary to
maintain appropriate glycemic control, these
findings could be used to help develop dosing rec-
ommendations when switching between these
basal insulins.
Methods
This retrospective evaluation was conducted at
the Endocrinology, Diabetes and Metabolism
Clinic at University of Colorado Health
(UCHealth) Anschutz Campus in Aurora,
Colorado. This is an urban, multidisciplinary
clinic which consists of 28 providers on an aca-
demic medical campus and provides comprehen-
sive management of diabetes and other endocrine
conditions. This study was approved by the
Colorado Multiple Institutional Review Board.
The objectives were to determine if dose adjust-
ments were required after switching from Gla-
100 to Gla-300 or insulin degludec and examine
how doses of Gla-100 were converted to Gla-300
or insulin degludec in clinical practice. Data were
collected from the electronic medical record
through an automatic report identifying all
patients with type 1 or type 2 diabetes seen in the
UCHealth Endocrine Clinic and transitioned
from Gla-100 to Gla-300 or insulin degludec
(U-100 or U-200) from March 2015 to March
2017. Patients also required a follow-up visit in

the UCHealth Endocrine Clinic 1–12 months
after transition, in order to have complete data
collected. Exclusion criteria included age < 18
years, pregnancy, and taking Gla-100 for less
than 3 months prior to transition. Baseline gly-
cated hemoglobin A1c (A1c) measurements were
only included for analysis if drawn within 1 month
prior to transition.
All data for the Gla-300 and insulin degludec
groups were evaluated separately. The primary
outcome was the difference between baseline Gla-
100 dose and dose of Gla-300 or insulin degludec
prescribed after the first follow-up visit within 1–12
months. Secondary outcomes included an analysis
of how doses were converted from Gla-100 to Gla-
300 or insulin degludec and a comparison of base-
line Gla-100 dose with doses of Gla-300 or insulin
degludec which participants reported taking when
returning for follow up. Additional secondary out-
comes included changes in A1c, fasting blood glu-
cose readings and rates of hypoglycemia from time
of transition to follow-up visit.
Baseline data collected at time of transition
included Gla-100 dose, A1c, self-monitoring of
blood glucose (SMBG) download data from the
previous month, rate of hypoglycemic events per
7 days, weight, other diabetes medications and
doses, and dose of new basal insulin at transition.
At the patient’s first follow-up visit taking place
1–12 months after transition, A1c, SMBG down-
load data from the previous month, rate of hypo-
glycemic events per 7 days, other diabetes
medications and doses, and doses of Gla-300 or
insulin degludec when reporting for visit, along
with doses prescribed after this visit were
recorded. If the patient’s first visit 1–12 months
after transition did not include an A1c measure-
ment, and the patient had a later visit within the
applicable timeframe which did include this
measurement then the subsequent visit was used
for data collection. Documentation of SMBG
readings and hypoglycemic events was taken
from provider encounter notes. Average fasting
blood glucose readings were manually verified
with each subject’s glucometer reading upload.
Dose changes were verified by comparing pro-
vider notes with medication prescription records.
For descriptive purposes, insulin doses were dif-
ferentiated as baseline Gla-100 dose (Point A),
dose of Gla-300 or insulin degludec prescribed
after initial visit (Point B), dose of Gla-300 or
insulin degludec which the patient was taking
when presenting for follow up 1–12 months after
journals.sagepub.com/home/tae 115
SM Pearson and JM Trujillo
transition (Point C), and dose of Gla-300 or
insulin degludec prescribed after follow-up visit
(Point D).
Statistics were computed using GraphPad InStat,
version 3.10, for Windows, GraphPad Software,
San Diego, California, USA. Wilcoxon rank sum
tests evaluated changes in median insulin doses
across time points. Paired t tests assessed changes
in A1c, average SMBG readings, and rates of
hypoglycemic events per 7 days. Descriptive sta-
tistics assessed baseline characteristics and con-
comitant medication changes. Using data from
the EDITION 2 trial (average insulin dose 0.67
units/kg/day, standard deviation 0.24), it was esti-
mated that 101 participants were needed in each
group in order to detect a 10% change with regard
to the primary outcome, with an 80% power and
an alpha value of 0.05.20 Since each subject served
as their own control in this study, 51 participants
were therefore needed in each the Gla-300 and
insulin degludec groups.
Results
A total of 131 subjects taking Gla-100 at baseline
were included in the study. There were 95 patients
prescribed Gla-300, and 39 were prescribed insulin
degludec. In the Gla-300 group, 55 of the 95 sub-
jects (58%) had a follow-up visit 1–12 months after
transition and were still taking Gla-300 at that time.
In the insulin degludec group, 17 of the 39 subjects
(44%) had a follow-up visit 1–12 months after tran-
sition and were still taking insulin degludec. The
mean time to follow up in those patients was 3.5
months in the Gla-300 group and 3.9 months in
the insulin degludec group (Figure 1).
Baseline demographic information for subjects is
listed in Table 1.
Figure 1.  Study enrollment.
Gla-100, insulin glargine U-100; Gla-300, insulin glargine
U-300.
Therapeutic Advances in Endocrinology and Metabolism 9(4)

Table 1.  Demographic data.

Gla-300 Insulin degludec

Total subjects 95 39
Men 48 (51%) 21 (54%)
Women 47 (49%) 18 (46%)
Type 1 diabetes 34 (36%) 18 (46%)
Type 2 diabetes 61 (64%) 21 (54%)
Average age (years) 57.7 54.8
Average disease duration (years) 19.5 19.5
Average weight (kg) 89.6 95.0
Average BMI (kg/m2) 31.2 31.0
Gla-300, insulin glargine U-300; BMI, body mass index.

Table 2.  Change in daily median insulin dose after follow-up visit versus baseline.

Baseline Gla-100 dose Point D p value

(Point A)

Gla-300 (n = 54)
Units; 30 (19–60) 34.5 (19–70) 0.01
median (IQR)
Units/kg; 0.35 (0.24–0.62) 0.39 (0.25–0.65) 0.01
median (IQR)
Insulin degludec (n = 17)
Units; 60 (27–90) 66 (26–76) 0.56
median (IQR)
Units/kg; 0.61 (0.34–0.99) 0.60 (0.30–0.86) 0.45
median (IQR)
Gla-300, insulin glargine U-300; IQR, interquartile range.

With regard to the primary outcome, median daily
basal insulin dose increased for patients transi-
tioned to Gla-300 from 30 [19–60 interquartile
range (IQR)] units at Point A to 34.5 (19–70
IQR) units at Point D (p = 0.01) (Table 2).
There was no significant change in median daily
basal insulin doses in the insulin degludec group,
from 60 (27–90 IQR) units at Point A to 66 (26–
76 IQR) units at Point D (p = 0.56). Results were
similar when computed as total daily units or
units per kilogram for each group (Table 2).
Doses across time points for the initial and fol-
low-up visits are shown in Figure 2.
The doses of Gla-300 at Point C were also signifi-
cantly higher than baseline doses of Gla-100 at
Point A when computed as either units or units
per kilogram, indicating that participants had
either self-titrated or been instructed to titrate
their dose before being seen again (Table 3). This
difference was not significant in the insulin deglu-
dec group.
The A1c, SMBG readings and rates of hypoglyce-
mia per 7 days did not significantly differ between
initial and follow-up visits for either the Gla-300
or insulin degludec groups (Table 4).
Baseline A1c measurements were 7.9% (63 ± 14
mmol/mol) and 8.1% (65 ± 14 mmol/mol) in the
Gla-300 and insulin degludec groups, respectively.
At the time of transition, the prescribed dose of
Gla-300 or insulin degludec at Point B did not
significantly differ from the previous dose of Gla-
100 at Point A (p = 0.73 and 0.28 respectively),
indicating that empiric dose adjustments were not
routinely prescribed (Figure 3).
In a post hoc subgroup analysis, it was found that
patients with type 1 diabetes who were switched to

116 journals.sagepub.com/home/tae
 SM Pearson and JM Trujillo

Gla-300 required significantly higher doses of basal

insulin at Point D compared with Point A (Table 5).
In patients with type 2 diabetes who were switched
to Gla-300, basal insulin dose requirements were
numerically higher, but not significantly different
between these time points. There were no significant
differences in basal insulin dose for patients with
either type 1 or type 2 diabetes switched to insulin
degludec from Point A to Point D.

Additional antihyperglycemic medications were

Figure 2.  Change in insulin doses across time points.
*p < 0.05 versus Point A.
YFor Point A to Point C, the comparison was conducted
with only 52 patients who had complete data points. For
these comparisons, Point A = 29 (19–59 IQR) units and
0.34 (0.24–0.64) units/kg, respectively. There were similar
findings when evaluated as units/kg.
Gla-100, insulin glargine U-100; Gla-300, insulin glargine U-300;
Point A = Gla-100 dose upon presentation to initial visit; Point
B = Gla-300 or insulin degludec dose prescribed after initial
visit; Point C = Gla-300 or insulin degludec dose at presentation
to follow-up visit; Point D = Gla-300 or insulin degludec dose
prescribed after follow-up visit; IQR, interquartile range.
added or dose escalated at some point during the
study period in 19% (10/54) of people taking
Gla-300, and 50% of these changes were in
bolus insulin regimens. Concomitant medica-
tions were discontinued or dose reduced in 9%
(5/54) of subjects, and 80% of these changes
were in bolus insulin regimens. Among the
patients who did not experience any changes in
concomitant medications, the increase in basal
insulin dose requirements was similar to that
seen in the overall Gla-300 population from
Point A to Point D, and the change in dose was
still statistically significant (Table 5). In the
insulin degludec group, 18% (3/17) of partici-
pants had in increase in dose or addition of con-
comitant antihyperglycemic medication, while
12% (2/17) had a dose reduction or discontinu-
ation. In patients who did not experience changes
in concomitant medications, there was still no

Table 3.  Insulin dose by time point.

Baseline Gla-100 Point B Point C Point D

dose (Point A)
Gla-300 (n = 54)
Units; median (IQR) 30 (19–60) 31.5 (18–60) 31.5 (19–61) 34.5 (19–70)
p value (versus Point A) 0.56 0.02* 0.01
Units/kg; median (IQR) 0.35 (0.24–0.62) 0.33 (0.25–0.58) 0.36 (0.25–0.63) 0.39 (0.25–0.65)
p value (versus Point A) 0.45 0.02* 0.01
Insulin degludec (n = 17)
Units; median (IQR) 60 (27–90) 60 (27–84) 60 (25–84) 66 (26–76)
p value (versus Point A) 0.27 0.24 0.56
Units/kg; median (IQR) 0.61 (0.34–0.99) 0.61 (0.33–1.05) 0.53 (0.30–0.87) 0.60 (0.30–0.86)
p value (versus Point A) 0.89 0.17 0.45
*For Point A to Point C, the comparison was conducted with only 52 patients who had complete data points. For these
comparisons, Point A = 29 (19–59 IQR) units and 0.34 (0.24–0.64) units/kg, respectively.
Point A = Gla-100 dose upon presentation to initial visit.
Point B = Gla-300 or insulin degludec dose prescribed after initial visit.
Point C = Gla-300 or insulin degludec dose at presentation to follow-up visit.
Point D = Gla-300 or insulin degludec dose prescribed after follow-up visit.
Gla-100: insulin glargine U-100; Gla-300: insulin glargine U-300; IQR: interquartile range.

journals.sagepub.com/home/tae 117
Therapeutic Advances in Endocrinology and Metabolism 9(4)

Table 4.  Changes in glycemic control.

Baseline Follow up p value

Gla-300
Hemoglobin A1c % (mmol/mol) (n = 34) 7.9% (63 ± 14) 8.0% (64 ± 16) 0.50
Overall average SMBG (mmol/l) (n = 29) 9.19 ± 1.88 9.54 ± 2.15 0.25
Average fasting SMBG (mmol/l) (n = 28) 9.17 ± 2.29 9.35 ± 2.22 0.70
Hypoglycemia (per 7 days) (n = 45) 1.15 ± 1.8 0.86 ± 1.3 0.34
Insulin degludec
Hemoglobin A1c % (mmol/mol) (n = 12) 8.1% (65 ± 14) 7.6% (60 ± 7) 0.19
Overall average SMBG (mmol/l) (n = 9) 10.7 ± 1.56 10.2 ± 1.64 0.41
Average fasting SMBG (mmol/l) (n = 7) 9.91 ± 2.85 9.78 ± 1.97 0.89
Hypoglycemia (per 7 days) (n = 12) 1.25 ± 1.5 1.27 ± 1.4 0.94

Baseline: visit at which patient was converted from Gla-100 to Gla-300 or insulin degludec.
Follow up: first visit 1–12 months after conversion from Gla-100 to Gla-300 or insulin degludec. Data were only included
for patients who were still taking Gla-300 or insulin degludec at this visit.
A1c, glycated hemoglobin A1c; Gla-300, insulin glargine U-300; SMBG, self-monitoring of blood glucose.

Figure 3.  Change in insulin dose at time of conversion.

Point A = Gla-100 dose upon presentation to initial visit.
Point B = Gla-300 or insulin degludec dose prescribed after initial visit.
Gla-100, insulin glargine U-100; Gla-300, insulin glargine U-300.

significant difference in basal insulin dose from
Point A to Point D.
Discussion
Patients transitioned from Gla-100 to Gla-300 had
increased basal insulin requirements, while basal
insulin requirements for those transitioned from
Gla-100 to insulin degludec were not significantly
different. The 15% increase in median dosage
requirements seen in the Gla-300 group was in
concordance with phase III trials which found par-
ticipants taking Gla-300 to have 12–18% higher
dosage requirements compared with those taking
Gla-100.2,8–11 Clinical trials found subjects taking
insulin degludec to have 11–12% lower dosage
requirements compared with those taking Gla-100,
and additional randomized, cross-over trials pub-
lished after the initiation of this study found partici-
pants with type 1 and type 2 diabetes to have 3%
and 4% lower dosage requirements when taking
insulin degludec than when taking Gla-100, respec-
tively. 15–18,21,22 However, our study was not pow-
ered to detect the anticipated dosage change in the
insulin degludec group due to small sample size. In
our study, doses were converted at an average 1:1
basis for both Gla-300 and insulin degludec, as is
recommended in the package insert for each
respective insulin. If people who are transitioned
from Gla-100 to Gla-300 or insulin degludec have
variable new insulin requirements, as our study and

118 journals.sagepub.com/home/tae
 SM Pearson and JM Trujillo

Table 5.  Subgroup analysis: change in daily median insulin dose after follow-up visit versus baseline.

Baseline Gla-100 Point D p value

dose (Point A)

Gla-300 (n = 54)
Type 1 diabetes (n = 18) Units; 17 (12–24) 17.5 (14–25) 0.04
median (IQR)
  Units/kg; 0.23 (0.17–0.35) 0.26 (0.22–0.35) 0.04
median (IQR)
Type 2 diabetes (n = 36) Units; 44 (24–71) 49 (26–74) 0.06
median (IQR)
  Units/kg; 0.41 (0.30–0.70) 0.49 (0.34–0.72) 0.08
median (IQR)
Total subjects without changes in Units; 28 (19–60) 33 (19–70) 0.03
concomitant medications (n = 39) median (IQR)
  Units/kg; 0.32 (0.24–0.62) 0.36 (0.26–0.62) 0.03
median (IQR)
Total subjects with changes in Units; 34 (23–60) 35 (24–58) 0.18
concomitant medications (n = 15) median (IQR)
  Units/kg; 0.41 (0.29–0.62) 0.42 (0.28–0.61) 0.08
median (IQR)
Insulin degludec (n = 17)
Type 1 diabetes (n = 8) Units; 26.5 (22–32) 26 (20–26) 0.16
median (IQR)
  Units/kg; 0.34 (0.30–0.36) 0.30 (0.25–0.35) 0.11
median (IQR)
Type 2 diabetes (n = 9) Units; 90 (75–100) 76 (68–100) 0.94
median (IQR)
  Units/kg; 0.99 (0.87–1.23) 0.86 (0.74–1.18) 0.99
median (IQR)
Total subjects without changes in Units; 70 (31–97) 68 (25–85) 0.70
concomitant medications (n = 12) median (IQR)
  Units/kg; 0.74 (0.37–1.19) 0.63 (0.34–1.01) 0.56
median (IQR)
Total subjects with changes in Units; 32 (25–60) 27 (26–66) 0.81
concomitant medications (n = 5) median (IQR)
  Units/kg; 0.34 (0.33–0.64) 0.37 (0.27–0.74) 0.63
median (IQR)
Point A = Gla-100 dose upon presentation to initial visit.
Point D = Gla-300 or insulin degludec dose prescribed after follow-up visit.
Gla-100, insulin glargine U-100; Gla-300, insulin glargine U-300; IQR, interquartile range.

previously completed trials suggest then converting
these doses on a 1:1 basis could be problematic
because patients may be subject to a period of
inadequate glycemic control. 2,8–11,15–18,21,22 No sig-
nificant changes were seen with regard to glycemic
control in our study, although these analyses were
also limited by low subject numbers.
In this study, 54% of individuals prescribed Gla-
300 or insulin degludec either did not fill the
prescription or did not have a follow-up visit in
the endocrine clinic within 1–12 months after
transitioning. In most cases, the absence of follow
up was due to insurance not covering the pre-
scribed insulin. Of individuals who filled the pre-
scription and had a follow-up visit within 1–12
months, the average time to follow up in the
endocrine clinic was around 3–4 months. This
standard follow up may have indicated that pro-
viders felt comfortable with their patients’

journals.sagepub.com/home/tae 119
Therapeutic Advances in Endocrinology and Metabolism 9(4)
glycemic control at the time of transition and did
not expect there to be significant changes when
switching from Gla-100 to Gla-300 or insulin
degludec. While the average A1c at the time of
transition was around 8% (64 mmol/mol), given
that many people seen in a specialized endocrine
clinic have complicated and difficult-to-control
disease, this may have demonstrated adequate
control based on their individual goals of care.
The time to follow up would also potentially be
longer if insulin conversion occurred in a primary
care clinic which does not specialize in diabetes
management. Additionally, as shown in Table 3,
there was a significant difference in insulin dose
when comparing Point A and Point C in the Gla-
300 group, which indicated patients had already
increased their dose prior to being seen for follow
up. If patients had already titrated their dose prior
to their visit then these patients may have found it
permissible to delay following up in clinic.
These findings must be interpreted with caution,
as this was a retrospective analysis based on data
collected from electronic medical records and is
therefore subject to bias. Many of the data for
SMBG readings and hypoglycemic episodes
were extracted from provider encounter notes,
which may not have been comprehensive.
External factors such as changes in concomitant
medications and medication adherence could
have impacted these results, and a number of
patients were lost to follow up. There was great
variability in baseline insulin doses, likely as a
result of the study assessing both patients with
type 1 and type 2 diabetes. This contributed to
the non-normal distribution of data and limited
statistical analyses. Post hoc subgroup analyses
were conducted for patients with both type 1
and type 2 diabetes, but they were not adequately
powered to draw conclusions. Our power calcu-
lation was conducted using insulin dosing data
from a previously published study, and it is pos-
sible that demographics for the patients in this
study differed from those in our clinic. The
anticipated sample size was not met in the insu-
lin degludec group for the primary outcome
measure, and it was difficult to assess changes in
glycemic control because many individuals’
insurances did not cover the newly prescribed
insulin. Therefore, patients were not always
transitioned, despite being written a prescription
for Gla-300 or insulin degludec. Interestingly,
this indicated that many providers in our clinic
chose to prescribe Gla-300 or insulin degludec
for clinical reasons (e.g. lower risk of nocturnal
120 journals.sagepub.com/home/tae
hypoglycemia or dosing flexibility) rather than
out of obligation due to insurance formulary
preferences.
Despite these limitations, the findings from this
study support evidence from phase III trials which
found patients taking Gla-300 to have higher dos-
age requirements than those taking Gla-100. As
the 15% dose increase seen in our study was in
line with the 12–18% increases reported in the
literature for Gla-300, these findings strengthen
support for empiric dose increases when switch-
ing from Gla-100 to Gla-300. Dose requirements
for individuals transitioned to insulin degludec
warrant further study, as we were not adequately
powered to detect changes in these doses.
Regardless, if patients are converted on a 1:1
basis from Gla-100 to either of these insulins, it is
important that providers ensure timely follow up
or instruct patients regarding dose titration to
prevent lapses in control.
Conclusion
Patients who transitioned from Gla-100 to Gla-
300 had increased basal insulin requirements
between visits, while basal insulin requirements
for those transitioned from Gla-100 to insulin
degludec were not significantly different.
Acknowledgements
We would like to thank Garth Wright for assis-
tance with statistical analysis
Funding
This research received no specific grant from any
funding agency in the public, commercial, or not-
for-profit sectors.
Conflict of interest statement
Dr Scott Pearson has no conflicts of interest to
disclose and Dr Jennifer Trujillo is a member of
the Sanofi Advisory Board.
ORCID iD
Scott M Pearson https://orcid.org/0000-0002-7427-
6734.
References
1. Centers for Disease Control and Prevention.
National diabetes statistics report: estimates of
diabetes and its burden in the United States
(Internet), Atlanta, GA: U.S. Department of
Health and Human Services, https://www.cdc.
gov/diabetes/pubs/statsreport14/national-diabetes-
report-web.pdf (2014, accessed 18 August 2016).

2. Brown MA, Davis CS, Fleming LW, et al. The
role of Toujeo®, insulin glargine U-300, in the
treatment of diabetes mellitus. J Am Assoc Nurse
Pract 2016; 28: 503–509.
3. Vora J, Cariou B, Evans M, et al. Clinical use of
insulin degludec. Diabetes Res Clin Pract 2015;
109: 19–31.
4. Gough SC, Bhargava A, Jain R, et al. Low-
volume insulin degludec 200 units/ml once
daily improves glycemic control similarly to
insulin glargine with a low risk of hypoglycemia
in insulin-naive patients with type 2 diabetes: a
26-week, randomized, controlled, multinational,
treat-to-target trial: the BEGIN LOW VOLUME
trial. Diabetes Care 2013; 36: 2536–2542.
5. Sanofi-Aventis U.S. LLC. Toujeo [Package
Insert]. Bridgewater, NJ: Sanofi-Aventis U.S.
LLC; 2015.
6. Novo Nordisc Inc. Tresiba [Package Insert].
Plainsboro, NJ: Novo Nordisk Inc.; 2015.
7. Riddle MC, Bolli GB, Home PD, et al. Efficacy
and safety of flexible versus fixed dosing intervals
of insulin glargine 300 U/mL in people with
type 2 diabetes. Diabetes Technol Ther 2016; 18:
252–257.
8. Matsuhisa M, Koyama M, Cheng X, et al. New
insulin glargine 300 U/ml versus glargine 100 U/
ml in Japanese adults with type 1 diabetes using
basal and mealtime insulin: glucose control and
hypoglycaemia in a randomized controlled trial
(EDITION JP 1). Diabetes Obes Metab 2016; 18:
375–383.
9. Terauchi Y, Koyama M, Cheng X, et al. New
insulin glargine 300 U/ml versus glargine 100
U/ml in Japanese people with type 2 diabetes
using basal insulin and oral antihyperglycaemic
drugs: glucose control and hypoglycaemia in a
randomized controlled trial (EDITION JP 2).
Diabetes Obes Metab 2016; 18: 366–374.
10. Home PD, Bergenstal RM, Bolli GB, et al. New
insulin glargine 300 Units/mL versus glargine
100 Units/mL in people with type 1 diabetes: a
randomized, phase 3a, open-label clinical trial
(EDITION 4). Diabetes Care 2015; 38: 2217–2225.
11. Ritzel R, Roussel R, Bolli GB, et al. Patient-
level meta-analysis of the EDITION 1, 2 and 3
studies: glycaemic control and hypoglycaemia
with new insulin glargine 300 U/ml versus
glargine 100 U/ml in people with type 2 diabetes.
Diabetes Obes Metab 2015; 17: 859–867.
12. Riddle MC, Bolli GB, Ziemen M, et al. New
insulin glargine 300 units/mL versus glargine
100 units/mL in people with type 2 diabetes
using basal and mealtime insulin: glucose control
journals.sagepub.com/home/tae 121
SM Pearson and JM Trujillo
and hypoglycemia in a 6-month randomized
controlled trial (EDITION 1). Diabetes Care
2014; 37: 2755–2762.
13. Goldman-Levine JD, Patel DK and Schnee DM.
Insulin degludec: a novel basal insulin analogue.
Ann Pharmacother 2013; 47: 269–277.
14. Korsatko S, Deller S, Koehler G, et al. A
comparison of the steady-state pharmacokinetic
and pharmacodynamic profiles of 100 and 200
U/mL formulations of ultra-long-acting insulin
degludec. Clin Drug Investig 2013; 33: 515–521.
15. Pan C, Gross JL, Yang W, et al. A multinational,
randomized, open-label, treat-to-target trial
comparing insulin degludec and insulin glargine
in insulin-naive patients with type 2 diabetes
mellitus. Drugs R D 2016; 16: 239–249.
16. Ratner RE, Gough SC, Mathieu C, et al.
Hypoglycaemia risk with insulin degludec
compared with insulin glargine in type 2 and type
1 diabetes: a pre-planned meta-analysis of phase
3 trials. Diabetes Obes Metab 2013; 15: 175–184.
17. Hollander P, King AB, Del Prato S, et al. Insulin
degludec improves long-term glycaemic control
similarly to insulin glargine but with fewer
hypoglycaemic episodes in patients with advanced
type 2 diabetes on basal-bolus insulin therapy.
Diabetes Obes Metab 2015; 17: 202–206.
18. Bode BW, Buse JB, Fisher M, et al. Insulin
degludec improves glycaemic control with
lower nocturnal hypoglycaemia risk than insulin
glargine in basal-bolus treatment with mealtime
insulin aspart in type 1 diabetes (BEGIN® Basal-
Bolus Type 1): 2-year results of a randomized
clinical trial. Diabet Med 2013; 30: 1293–1297.
19. Lamos EM, Younk LM and Davis SN.
Concentrated insulins: the new basal insulins.
Ther Clin Risk Manag 2016; 12: 389–400.
20. Yki-järvinen H, Bergenstal R, Ziemen M,
et al. New insulin glargine 300 units/mL versus
glargine 100 units/mL in people with type 2
diabetes using oral agents and basal insulin:
glucose control and hypoglycemia in a 6-month
randomized controlled trial (EDITION 2).
Diabetes Care 2014; 37: 3235–3243.
21. Lane W, Bailey TS, Gerety G, et al. Effect of
insulin degludec vs insulin glargine U100 on
hypoglycemia in patients with type 1 diabetes:
the SWITCH 1 randomized clinical trial. JAMA
2017; 318: 33–44.
22. Wysham C, Bhargava A, Chaykin L, et al. Effect
of insulin degludec vs insulin glargine U100 on Visit SAGE journals online
hypoglycemia in patients with type 2 diabetes: journals.sagepub.com/
home/tae
the SWITCH 2 randomized clinical trial. JAMA
2017; 318: 45–56. SAGE journals