4 research outputs found
Combined sulphonylurea and insulin treatment for type 2 diabetes mellitus : metabolic and electrophysiological studies
Type 2 diabetes is a prevalent disorder characterized by elevated blood
glucose levels and associated with increased morbidity from micro- and
macrovascular complications. Lowering of blood glucose has been shown to
reduce the incidence of such complications. Since the patient population
is heterogeneous and the disease progresses with time, multiple therapies
become necessary in the long-term. Combining sulphonylurea (SU) with
insulin is one option, and various aspects of such therapy were studied
in this thesis.
Study I was a double-blind randomized study where 175 patients with
secondary failure to oral agents were started on insulin in addition to
oral glibenclamide. Glycaemic control improved, mean HbA1c 9.65% to 7.23%
at four months. A high HbA1c and preserved insulin sensitivity at
baseline were associated with a greater response to insulin combined with
SU. Thereafter SU was, replaced by placebo in a majority of the patients,
while a smaller control group continued on SU. the placebo/SU withdrawal
group, fasting blood glucose (FBG) increased >10% in 79% within weeks,
and 60% of the group were classified as SU responders, defined as >40%
increase in FBG. Multivariate logistic regression analyses showed no
clinically useful patient characteristics that identified SU responders
at baseline, but long diabetes duration and absence of GAD antibodies
were associated with beneficial response. A short period of SU withdrawal
appeared as a useful test to determine whether a patient still benefits
from SU. In Study II 80 patients with secondary SU failure were
randomized to two principally different insulin regimens - bedtime NPH or
preprandial regular insulin - in addition to SU. Both regimens had
similar effects on HbA1c but weight gain was more pronounced in patients
on pre-prandial insulin. Patients who participated in Studies I and 11 at
Danderyd Hospital were included in a follow-up over a median of 69 months
(Study III). During this time four patients died and six were
reclassified as having type I diabetes. Glycaemic control was maintained
at an improved level with mean HbA1c 7.4% (SD 1.1) and weight stabilized
after an initial gain of approximately 5 kg the first year. When
necessary metformin was added to SU and insulin, and at 54 months about
half were on such triple therapy.
Hypoglycaemia is a limiting factor in attaining glycaemic goals in
diabetes. Physiological responses to low blood glucose include decrease
of insulin secretion and increase of counterregulatory hormones, the most
important being glucagon and adrenaline. Study IV showed that
glibenclamide affected these responses during insulin-induced
hypoglycaemic clamp experiments in 13 patients with type 2 diabetes. When
SU was present, insulin secretion was less suppressed and the glucagon
response to hypoglycaemia was blunted. In Study V measurements of QT
intervals were used to study the effects of hypoglycaemia on cardiac
repolarization in 13 patients. Mean QT intervals and QT dispersion
increased significantly during hypoglycaemia, indicating an increased
risk of arrhythmia at low blood glucose values. No significant changes
were seen between the two experiments with or without glibenclamide but
the number of patients was too small to give conclusive data regarding
this issue.
In summary, more studies regarding SU effects on glucagon secretion and
cardiac repolarization are needed and should include comparisons of
different SU derivatives. The present studies provide both pros and cons
for combining glibenclamide with insulin in patients with type 2 diabetes
who no longer can attain glycaemic goals on oral therapy alone; but the
advantages seem to outweigh the possible disadvantages
Cost-effectiveness of switching to insulin degludec from other basal insulins: evidence from Swedish real-world data
<p><b>Objectives:</b> Health economic analysis from a healthcare and societal point of view was conducted to assess the cost-effectiveness of insulin degludec (IDeg) after switching from other basal insulins in people with type 1 diabetes.</p> <p><b>Material and methods:</b> This was a prospective, open-label, single arm, observational follow-up from August 2013 to October 2015 of 476 consecutive patients at Danderyd Hospital (Stockholm, Sweden) who switched to IDeg from other basal insulins (99% basal insulin analogs). The IMS CORE Diabetes Model (CDM) was used to predict the cost-effectiveness of life-long treatment with IDeg vs. other basal insulins, based on a Swedish setting.</p> <p><b>Results:</b> Mean (SD) duration of follow-up was 21.7 (6.0) weeks. Mean HbA<sub>1c</sub> decreased by 2.7 mmol/mol, mean basal insulin dose decreased by 13.1% (<i>p</i> < .0001), and mean bolus insulin dose decreased by 7.5% (<i>p</i> < .0001) after switching. Frequencies of non-severe daytime hypoglycemia and non-severe nocturnal hypoglycemia decreased by 12% (<i>p</i> = .0127) and 53% (<i>p</i> < .0001) respectively and severe hypoglycemia was reduced by 62% (<i>p</i> = .0225). The CDM predicted a gain in life expectancy of 0.33 years, a discounted gain in quality-adjusted life-years (QALYs) of 0.54, and lower estimated direct lifetime healthcare costs of SEK 22,757 for patients switching to IDeg. The incremental cost-effectiveness ratio (ICER) showed IDeg as dominant (i.e. higher effectiveness with a lower cost). Sensitivity analyses confirmed the results.</p> <p><b>Conclusion:</b> Based on this prospective, real-world, follow-up and using the CDM, it was estimated that switching to IDeg from other basal insulins translated into QALY gains including improved life expectancy and health-related quality of life, as well as dominant ICER, meaning cost-savings for the healthcare system. However, the study is limited by its observational design. Extrapolation into the future is only estimated since the actual treatment effect cannot be projected with certainty.</p
Clinical use of insulin degludec
The limitations of current basal insulin preparations include concerns related to their pharmacokinetic and pharmacodynamic properties, hypoglycaemia, weight gain, and perception of management complexity, including rigid dosing schedules. Insulin degludec (IDeg) is a novel basal insulin with improved pharmacokinetic and pharmacodynamic properties compared to insulin glargine (IGlar) including a long half-life of ∼25 h and a duration of action >42 h at steady state, providing a flat and stable blood glucose-lowering effect when injected once daily. Evidence from phase 3a clinical trials with a treat-to-target design in patients with type 1 and type 2 diabetes has shown that IDeg has similar efficacy to IGlar, with a 9% and 26% reduction in risk of overall and nocturnal hypoglycaemia, respectively (in the pooled population) during the entire treatment period, and a 16% and 32% reduction during the maintenance period, respectively. Given its pharmacodynamic properties, IDeg offers a broad dosing window, allowing for flexible dose administration, if required. Two different formulations of IDeg are available (100 units/mL [U100] and 200 units/mL), the latter providing the same IDeg dose as the U100 formulation in half the injection volume. The unique pharmacokinetic profile of IDeg facilitates glycaemic control while minimising the risk of nocturnal hypoglycaemia