an analysis of early insulin glargine added to metformin with or without sulfonylurea: impact on...
TRANSCRIPT
An analysis of early insulin glargine
added to metformin
with or without sulfonylurea: impact
on glycaemic control
and hypoglycaemia
Case scenario
• The patient is 45 years old man , is known
case of type 2 diabetes from 3years ago with
inadequate glycaemic control , who treated
with metformin , and admitted here for
control of diabetes
PICO
P : Patient with type 2 diabetes with inadequate
glycaemic control
I : early insulin glargine adding
C : later insulin glargine adding
O : glycaemic control and hypoglycaemia
Keywords
Type 2 DM
Early insulin therapy
Basal insulin
Introduction
• In 2009
• American Diabetes Association (ADA)
• European Association for the Study of Diabetes
(EASD)
• Consensus statement on the initiation and
adjustment of therapy for type 2 diabetes
Introduction
• Glycaemic control HbA1c <7.0%
• These tier 1 interventions included lifestyle
modification and metformin (MET)
concomitantly initiated at step 1
Introduction
• The addition of either basal insulin or
sulfonylurea (SU) therapy to MET at step 2 (if
glycaemic goals are not achieved with MET
alone)
Introduction
• the addition or intensification of insulin
therapy as needed to attain glycaemic control
at step 3
Introduction
• In routine clinical practice
• Insulin therapy is more often initiated after
two or more oral antidiabetic drugs (OADs)
have proven inadequate to achieve or
maintain glycaemic control.
Introduction
• The reasons for delaying insulin initiation are varied,
but may include
• patient and physician perceptions
• Insulin therapy regimens are too complex self
administering injections
• Fears regarding side effects such as hypoglycaemia
and weight gain.
Introduction
• For these reasons, we sought to use the
extensive clinical trial database of insulin
glargine to assess the observed clinical
outcomes of earlier versus later basal insulin
initiation on glycaemic control and safety after
24 weeks of treatment.
Introduction
• to compare clinical outcomes after initiating insulin
glargine in patients with uncontrolled type 2
diabetes on 0 or 1 OAD versus 2 OADs at baseline
• We also performed a meta-analysis to evaluate the
robustness of the pooled analysis and to control for
differences in sample size.
Methods
• In total, 63 randomized controlled trials evaluating
insulin glargine in patients with type 2 diabetes
• These studies were performed between 1997 and
2007
• Individual patient data were available for inclusion
in pooled analyses.
Methods
• prospective, randomized, controlled trials of ≥24
weeks’ duration
• Enrolled adult patients with type 2 diabetes with
inadequate glycaemic control
• Basal insulin was given once daily, with no
concomitant prandial or bolus insulin administration
Methods
• Insulin glargine was initiated at 10 U/days and
dose adjustment to achieve fasting plasma
glucose levels <100 mg/dl
• Studies were conducted according to Good
Clinical Practice and in accordance with the
Declaration of Helsinki.
Methods
• Twelve studies met these eligibility criteria;
however, one study discontinued
thiazolidinediones abruptly at baseline and
was not included in this analysis.
• Therefore, data from 11 studies were used in
the pooled analysis
Clinical Outcomes
• Week 24 HbA1c level and change from baseline
• The percentage of patients reaching a target
HbA1c level of ≤7.0%,
• Change in body weight from baseline
• Insulin dose at endpoint
• Symptomatic and severe hypoglycaemic incidence
Clinical Characteristics and Patient emographics
• Of 3801 patients, a total of 2171 in the 11 selected studies were treated with insulin glargine and therefore inclusion in the pooled analysis.
• 1.8% of patients were taking no OAD
• 45.2% took 1 OAD
• 52.2% took 2 OADs
• 49.9% of all patients were taking MET + SU
• 36.5% of patients took an SU only
• 8.5% took a MET only.
Glycaemic Outcomes
• HbA1c ≤ 7.0% at week 24 after the addition of basal insulin
• Results were similar between the 0/1 OAD group and the 2
OAD group (54.7% vs. 56.7%, respectively, p = 0.0541).
• MET-only group (68.1%) other groups (50.4 and 56.4% for
SU only and combination groups).
• MET-only group experienced the largest mean
improvement in HbA1c from baseline
Weight Change
• Weight gain from baseline to week 24 was not
significantly different
• The MET-only group had the numerically
lowest weight gain over 24 weeks after basal
insulin initiation.
Insulin Dose
• The stable weight-based insulin doses for patients
on 0/1 OAD and on 2 OADs were similar
• The mean insulin dose per kilogram in patients on
MET only was higher than that for patients on SU
only or on SU + MET combination therapy
Hypoglycaemia
• Symptomatic
• Confirmed symptomatic: glucose <50 mg/dl
• Severe hypoglycaemia
• Incidence and rates were low overall
Discussion
• Patients taking MET alone The greatest HbA1creductions.
largest proportion of patients achieving
glycaemic goal. The lowest rate of symptomatic and severe
hypoglycaemia. The lowest weight gain.
limitation
• only studies of insulin glargine
• outcomes following 24weeks of treatment
• We did not assess if any changes did occur in
OADs during the course of this study
Materials and Methods
I. The Medline, Embase and Cochrane Library
electronic databases were searched
II. English language papers from January 2000 to
August 2010
Inclution criteria:(i) primary studies in adults with T2DM with
insulin being at least one of the interventions (ii) studies concerned with insulin initiation and
intensification,(iii)Randomized clinical trials, observational studies,
economic evaluations, systematic reviews and meta-analyses,
(iv)At least one baseline and post-treatment efficacy, quality of life (QoL), safety and economic outcomes of interest
outcome
(i) change from baseline in HbA1c
(ii) change from baseline in BG
(iii) QoL/treatment satisfaction (TS)
(iv) rate of hypoglycaemia,
(v) change from baseline in weight
(vi) economic cost
Study Characteristics
40 studies were included
27 were randomized controlled trials (RCTs),
11 were observational studies
2 were modelling studies.
Patient Characteristics
Most of the studies included patients with ages
ranging from 30 to 80 years.
In a majority of studies, the mean HbA1c level at
baseline was >7% with values ranging from 7.5 to 12%.
The body mass index (BMI) of included patients was
≤35 kg/m2, except for a few studies that included
patients with BMI ≤ 40 kg/m2.
Clinical OutcomesHbA1c at baseline and endpoint were reported in 37 of the 40
included studies
The mean reduction in HbA1c levels was more than 1% in all
patients initiating insulin therapy
The mean HbA1c reduction was significantly more in patients
on insulin or insulin added to OADs compared to patients on
OADs alone
Early initiation of insulin therapy was associated with greater
reductions in HbA1c levels from baseline.
Quality of Life
were reported in six studies and was the
primary outcome of one study.
No significant difference was reported for QoL
outcomes between insulin and OADs
similar for OADs alone vs. OADs in combination
with insulin
Adverse events
Hypoglycaemia and weight gain were the main
adverse events that were reported in most studies
Hypoglycaemic rates or events were reported to
be lower with insulin initiation as compared to OADs
alone
Incidence of hypoglycaemic events was similar for
the insulin types
Adverse events
Weight gain was observed with all insulin across studies
There were different reports regarding weight gain for
studies comparing OADs alone and insulin initiation
- 3.36 kg gained with insulin + metformin
- 10.10 kg gained with triple OADs
Similar weight gain for OADs and insulin
No weight gain with OADs compared with insulin initiation