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Diabetes Management
rapid-acting, short-acting, intermediate-acting, long-acting, and pre-mixed Intensification of Basal Insulin by
insulins. To use insulin therapy most effectively, the regimen must be Adding Bolus Insulin
matched to the individual patient, considering his or her lifestyle needs Basal–bolus therapy with MDIs or an insulin pump is the most
and physical and mental capabilities, in addition to matching the body’s physiological approach to insulin therapy. When basal insulin alone in
physiological requirements. combination with an OAD fails to control hyperglycemia, addition of
prandial insulin is required. Most patients will ultimately require prandial
Several studies have compared insulin detemir with either insulin glargine insulin in addition to basal insulin as beta-cell function declines. Basal–
or NPH.
36–40
In a 26-week randomized, parallel-group trial including 476 bolus therapy using a rapid-acting insulin analog at mealtimes in addition
patients with type 2 diabetes, addition of twice-daily insulin detemir to oral to a basal insulin analog is highly effective and allows flexibility in both the
therapy achieved a decrease in HbA
1c
of 1.8% compared with a decrease timing and amount of prandial insulin dosing. Glycemic control can be
in 1.9% with NPH.
36
In both treatment groups, 70% of participants achieved improved with insulin analog therapy without excessive weight gain and
a corrected HbA
1c
≤7.0%. In addition, there was a trend in which the hypoglycemia. Some patients may get by with the addition of prandial
proportion achieving this without hypoglycemia became higher with insulin only before the largest meal of the day, while others will require
insulin detemir than with NPH insulin (34 versus 25%; p=0.052 [figures intensive basal–bolus therapy with prandial insulin before each meal. A
corrected]). Overall, compared with NPH insulin, the risk for all potential concern for some patients is the need for multiple injections.
hypoglycemia with insulin detemir was reduced by 47% (p<0.001) and
nocturnal hypoglycemia by 55% (p<0.001). At the end of the study, patients A common pitfall with basal insulin is increasing the dose too much before
in the insulin detemir group had gained 1.6kg less weight and had 47% adding prandial insulin. This does not match the physiological needs, and
lower risk for hypoglycemia. Treatment for 52 weeks with insulin glargine predisposes the patient to fasting hypoglycemia without reaching the
added to oral therapy showed a similar reduction in HbA
1c
levels to that target HbA
1c
level. A rule of thumb is that a patient should not be
achieved with NPH (-0.8 versus -0.7%), with lower rates of symptomatic advanced to more than 0.5 units/kg bodyweight for basal insulin without
hypoglycemia (33 versus 51%; p=-0.027).
40
first considering the addition of a rapid-acting insulin (e.g. 0.1 units/kg) with
meals.
45
Insulins available for prandial coverage include regular insulin and
The findings associated with insulin detemir were confirmed in the open- the rapid-acting insulin analogs. The rapid-acting analogs, including aspart,
label, prospective, observational Predictable Results and Experience in lispro, and glulisine, allow closer approximation of physiological insulin
Diabetes through Intensification and Control to Target: An International secretion and also allow for flexible dosing/dosing closer to meal times.
46,47
Variability Evaluation (PREDICTIVE) study (n=5,604), which enrolled 293
patients with type 2 diabetes who were switched to insulin detemir after A series of large studies have investigated the addition of bolus insulin
treatment with NPH insulin or glargine in addition to oral agents.
41–44
Oral dosing to basal insulin while taking OADs over periods of six months to one
regimens remained the same and the number of daily injections did not year in populations of 271–505 patients with type 2 diabetes who, prior to
change. Regardless of previous basal insulin regimen, patients achieved the study, had received a variety of diabetes treatments.
38,48–51
In some of
better glycemic control with insulin detemir, as shown by HbA
1c
these trials insulin detemir was compared with either insulin glargine or
decreasing by 0.2% (p<0.05) among patients previously receiving NPH and NPH insulin as the basal dose with insulin aspart or human soluble
by 0.6% (p<0.0001) for those who had originally received glargine. The insulin as the bolus treatment with concomitant oral agents such as
incidence of hypoglycemia was also significantly reduced (p<0.0001). In biguanides (metformin), sulfonylureas (glimepramide), thiazolidinediones
addition, FPG decreased by 1.4mmol/l in both the NPH and glargine groups (rosiglitazone), or acarbose. In each case HbA
1c
levels were improved by
(p<0.0001). This improvement was accompanied by a weight decrease of the use of bolus treatment, but the different basal treatments tended to
0.7kg (p<0.01) in those previously treated with NPH and 0.5kg (p<0.05) in produce non-significantly different outcomes for this parameter. An
patients who switched from glargine. The incidence of hypoglycemia was example was a trial by Hollander et al.
48
in which 319 patients with type 2
also reduced significantly (p<0.0001). These data provide important proof diabetes were randomized to either long-acting insulin detemir or glargine
of principle that glycemic control can be improved with modern insulin as basal therapy and insulin aspart given as a bolus dose at meal times
analog therapy without excessive weight gain and hypoglycemia.
41
(prandial). The bolus dose decreased HbA
1c
levels, but after 52 weeks
of treatment there was no marked difference between the two basal
A subgroup analysis of the German cohort from the PREDICTIVE study treatments (HbA
1c
7.19 and 7.03% for detemir and glargine, respectively,
assessed patients over a three-month period who started on OADs only mean difference 0.17%, 95% confidence interval [CI] -0.07–0.40).
(n=1,321), NPH insulin ± OADs (n=251), or insulin glargine ± OADs (n=260)
and were transferred to insulin detemir with OADs.
44
After three months In another study on 387 patients with type 2 diabetes treated for 26 weeks
of insulin detemir, hypoglycemic events/patient were reduced by 84, 80, with insulin detemir or insulin glargine as the basal treatment with insulin
and 90%, respectively, and no major hypoglycemic events were reported. aspart as the bolus before meals and OADs, changes in HbA
1c
from
HbA
1c
and FBG were significantly reduced from baseline in each of the baseline were significantly different in both groups (-1.1 and 1.3%,
subgroups (p<0.0001 for both). These data were said to confirm the short- respectively; p<0.0001).
50
In a study conducted by Haak et al.,
37
a
term safety and efficacy of insulin detemir ± OADs in a real-world scenario. population of 505 patients with type 2 diabetes was randomized to either
long-acting insulin or NPH insulin as the basal dose with OADs, and both
These studies showed that the modern insulin therapies detemir and groups were given a bolus of insulin aspart. After 26 weeks of treatment
glargine showed improved efficacy over NPH with decreased variability there was no significant difference in FPG levels between the groups
and hypoglycemic events without causing excessive weight gain. (p=0.66), but levels of HbA
1c
were significantly reduced in both groups
42 US ENDOCRINOLOGY
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