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