Table of Contents  

Kaddaha: Initiation of insulin glargine plus oral antidiabetic drugs in patients with type 2 diabetes uncontrolled on premixed insulin

Introduction

The prevalence of diabetes is increasing phenomenally and has been considered a major health concern of the twenty-first century by the World Health Organization and International Diabetes Federation (IDF).1 Over the last three decades there has been a dramatic increase in the prevalence of type 2 diabetes mellitus (T2DM) in Arabic-speaking countries, a trend that is in line with global prevalence data.2 According to 2012 IDF statistics, in Middle East and North African countries an estimated 10.9% of the population is suffering from T2DM (34 million), of whom 52.9% are unaware of the disease and are left undiagnosed.3 Among the Arabic-speaking countries, Kuwait has the highest prevalence rate of T2DM, 23.86%, with > 16% of the adult population being affected by the disease,4 whereas in the United Arab Emirates (UAE) and Oman the prevalence rates are 18.87% and 10.16%, respectively.3

Glycaemic control in most patients with T2DM remains an elusive goal because the disease is progressive and often oral antidiabetic agents (OADs) that are initially successful may fail later, necessitating aggressive management strategies.5 The UK Prospective Diabetes Study6 found that patients newly diagnosed with T2DM have 50% normal insulin secretion, which further reduces to < 25% after 6 years, eventually necessitating insulin supplementation therapy for good glycaemic control.7 Data from several large randomized studies have established that aggressive management of diabetes with insulin therapy can significantly reduce diabetes-related micro- and macrovascular complications.6,812 Thus, early use of insulin therapy is increasingly being considered as an integral part of an adequate diabetes management strategy.13

Several international guidelines, such as those published by the American Diabetes Association (ADA)/European Association for the Study of Diabetes14 as well as those of the American Association of Clinical Endocrinologists/American College of Endocrinology,15 advocate initiation of insulin treatment early in the disease if lifestyle management and monotherapy fail to provide optimal glycaemic control. However, the question of an optimal insulin regimen for initiation in patients failing to achieve glycaemic control with other interventions remains unanswered. In clinical practice, patients with T2DM may be initiated on insulin regimens using pre-mixed insulin or basal insulin, either alone or in combination with OADs.16 It is estimated that, worldwide, nearly 40% of patients with diabetes on insulin therapy are treated with pre-mixed insulin.17 Nevertheless, currently there is limited information regarding the subsequent intensification/progression of therapy in T2DM patients failing to achieve glycaemic control with established pre-mixed insulin regimens.18

Insulin glargine is a basal insulin analogue characterized by the lack of a pronounced peak of insulin concentration, duration of action of 24 hours and relatively low variability between patients following a single-dose administration.19 Glargine-based insulin regimens are simple and well tolerated in both primary and secondary care settings and, when initiated, they achieve a clinically meaningful reduction in glycated haemoglobin (HbA1c) levels.20,21 Evidence suggests that insulin glargine is more effective in reducing HbA1c than pre-mixed insulin,16 with a significantly lower risk of hypoglycaemia and weight gain.18,22 Treatment with insulin glargine in patients inadequately controlled on pre-mixed insulin may provide improved glycaemic control, tolerability and treatment satisfaction.2325 Previous studies have shown significant improvement in glycaemic control, with a lower incidence of hypoglycaemia, when patients insufficiently controlled on pre-mixed insulin were switched to insulin glargine plus OADs,25 or when insulin glargine plus OADs were compared with a twice-daily pre-mixed therapy in insulin-naive patients insufficiently controlled on OADs.16 Furthermore, the cost of achieving an equivalent reduction in HbA1c has been reported to be 34% less with insulin glargine plus OADs than with twice-daily, biphasic insulin aspart with no OADs.16

Despite the availability of such evidence favouring the use of insulin glargine in patients inadequately controlled on pre-mixed insulin, its role in disease management in patients from the Middle East is unclear. As a result of the paucity of clinical evidence about the use of insulin glargine in patients from this region, there is a lack of consensus and availability of information regarding appropriate therapeutic options for T2DM patients failing on pre-mixed insulin-based regimens. In light of the burgeoning burden of diabetes in the Middle East and North Africa, it is important to initiate and intensify appropriate insulin therapy at the appropriate time to avoid a massive burden of diabetes complications. Thus, the need for clear clinical evidence evaluating available insulin options, especially insulin glargine, in the T2DM population from the Middle East prompted this study. The aim of the current study was to observe the effectiveness and safety of insulin glargine administered in combination with OADs in patients with T2DM not controlled on pre-mixed insulin-based therapy in the UAE, Oman and Kuwait. The primary objective was to observe the effectiveness of a insulin glargine-based regimen in combination with OADs in T2DM patients in terms of HbA1c improvement after a follow-up period of 16 weeks. The secondary objective was to observe the proportion of patients reaching the target HbA1c in the study population and to describe the safety profile.

Methods

Study design

This was a 16-week, non-interventional, prospective, multicentre, non-comparative and post-authorization study of patients with T2DM conducted in the UAE, Oman and Kuwait. The study was conducted in accordance with the guidelines for Good Epidemiology Practice,26 the principles of the Declaration of Helsinki27 and the local regulations of the institutional review board/institutional ethics committee. Written, signed informed consent was obtained from each patient enrolled in the study.

Investigators and study population

A total of 35 investigators/physicians participated in the study. Investigators were selected based on their specialty and experience from an exhaustive list of physicians treating diabetes in the Gulf. Each selected physician recruited consecutive patients who met the inclusion criteria during his/her consulting sessions. Adult patients with T2DM who had failed to achieve the optimum HbA1c level (HbA1c < 7%) after 3–12 months on pre-mixed insulin therapy, and who, as a result, were prescribed insulin glargine plus OADs, were eligible for the study. There was provision to include patients in whom the addition of a single dose of short-acting insulin to insulin glargine-based therapy was clinically warranted. Pregnant or lactating patients as well as patients with moderate/severe renal impairment, impaired liver function, HbA1c > 11%, type 1 diabetes mellitus, or a contraindication or hypersensitivity to used medication were excluded from the study.

Data collection

Data were collected by the investigators or staff of the study using case report forms. At baseline, demographic characteristics including age, gender, weight and body mass index (BMI) were recorded. In addition, data on prior medication, history of diabetes, lipid profile, HbA1c, fasting blood glucose (FBG), associated morbidities and duration of diabetes were collected. HbA1c and FBG values of all the patients were collected at baseline and at the end of the 16-week follow-up period.

Effectiveness and safety

The primary effectiveness end point was to determine change in HbA1c levels in patients receiving insulin glargine in combination with OADs at 16 weeks. FBG was also analysed in this population during the study period. The secondary effectiveness end point was the proportion of patients achieving HbA1c <7% at 16 weeks. In addition to the number of hypoglycaemic episodes experienced by the study population during the study, safety was evaluated for all the adverse events (AEs) and serious adverse events (SAEs) either related or unrelated to study medication. A subgroup analysis was performed to investigate the mean reduction in HbA1c and FBG in patients who were using insulin glargine alone and those in whom short-acting insulin had been added. The proportion of patients in each treatment subgroup achieving HbA1c < 7% at 16 weeks was also evaluated.

Statistical analysis

All the enrolled patients in the study were defined as the ‘overall population’. All patients who had satisfied the inclusion and exclusion criteria and for whom HbA1c values were available at baseline and at the end of therapy were defined as the ‘eligible population’, whereas all patients who had satisfied the inclusion and exclusion criteria and for whom HbA1c values were available at baseline and at the end of 4-month follow-up with at least two available FBG values were defined as the ‘evaluable population’.

The total sample suggested was 360 patients. Hammer and Klinge23 reported that HbA1c in T2DM patients who were on pre-mixed insulin alone improved from 8.2% to 7.1%, with a mean decrease of 1.1 + 1. HbA1c in T2DM patients who were on pre-mixed insulin plus OADs improved from 8.3% to 7.2%, with a mean decrease of 1.2+1. Proposing β = 0.20 and α = 0.05 and assuming a drop in HbA1c of 0.4 with a standard deviation (SD) of 1, the estimated standardized effect size will be 0.5. From the table In Designing Clinical Research,28 the number of patients needed to prove this hypothesis is 100 per treatment group. The total sample suggested was 360 patients, taking into account a potential dropout rate of 20%, to enable the analysis of three subgroups of interest. The subgroups of interest are (1) patients who were on pre-mixed insulin alone; (2) patients who were on pre-mixed insulin plus metformin; and (3) patients who were on pre-mixed insulin plus a sulfonylurea. However, in practice, recruitment did not match the planned sample size calculation per subgroup; hence the analysis of different subgroups was not completed. Data were summarized using mean, median, SD and range for continuous parameters and counts and percentages for categorical parameters. All statistical tests were performed using two-tailed tests at a 5% level of significance and 95% confidence intervals. The statistical significance of between-group differences was computed using the two-sided chi-squared test, t-test, analysis of variance (ANOVA) or non-parametric tests, as appropriate. ANOVA was performed to assess between-group differences followed by a post hoc leas significant difference test. Paired t-tests and repeated ANOVA were used to assess the change from baseline in HbA1c and FBG, respectively,. The statistical analyses were performed using SPSS version 18.0 (SPSS, Inc., Chicago, IL, USA).

Results

This study was conducted during the period April 2009 to June 2010, enrolling 188, 119 and 90 patients from the UAE, Oman and Kuwait, respectively.

Patient enrolment

Of the total of 397 patients enrolled for the study, 13 did not meet the inclusion/exclusion criteria and in nine HbA1c values were not available; therefore, 375 patients were included in the eligible population. Furthermore, 361 patients were included in evaluable population for analyses as data from 14 patients could not be used (Figure 1). A subgroup analysis was performed to compare the insulin glargine group and the insulin glargine with short-acting insulin group in the evaluable population. Among 357 patients (for four patients information about OAD and short-acting insulin was not available), 288 (80.7%) were treated with insulin glargine alone and the remaining 69 (19.3%) patients received insulin glargine along with a short-acting insulin.

FIGURE 1

Patient enrolment.

HMJ-441-fig1.jpg

Demographic characteristics

Table 1 shows demographic and baseline characteristics of the eligible, evaluable and overall population. In this observational study there was no fixed study visit schedule and data were gathered in routine clinical practice, however, the physicians were asked to report updated participant data on a 4-month cycle. In the overall population, approximately 60% were male and 40% were female, with mean age of 50.51(SD ± 9.86) years. The mean weight and BMI was 81.15 (SD ± 13.04) kg and 29.47 (SD ± 4.94) kg/m2, respectively. The mean duration of diabetes was 10.67 (SD ± 5.68) years and approximately 77% of the patients had a family history of diabetes. Previous medication in the majority of patients (96.5%) comprised pre-mixed insulin; 64.7% patients were taking metformin and 46.45% were being treated with sulfonylureas. Neuropathy was the most common coexisting complication reported (38.2%). Of the total population, 67% of patients reported ongoing morbidities and 5% of patients reported past morbidities.

TABLE 1

Patient demographic characteristics

Parameter Eligible population (n = 375) Evaluable population (n = 361) Overall population (n = 397)
Male, n (%) 224 (59.7) 217 (60.1) 236 (59.4)
Age (years), mean (SD) 50.31 (± 9.79) 50.26 (± 9.66) 50.51 (± 9.86)
Weight (kg), mean (SD) 81.22 (± 13.10) 81.23 (± 12.77) 81.15 (± 13.04)
BMI (kg/m2), mean (SD) 29.46 (± 4.96) 29.44 (± 4.76) 29.47 (± 4.94)
Co-existing complications of diabetes, n (%)
 Macroangiopathy 46 (14.2) 44 (14.1) 48 (14.1)
 Retinopathy 71 (21.8) 66 (21.2) 74 (21.8)
 Nephropathy 57 (17.8) 57 (18.3) 59 (17.4)
 Neuropathy 124 (38.2) 118 (37.9) 130 (38.2)
 Others 10 (3.1) 10 (3.2) 11 (3.2)
Family history of diabetes, n (%) 290 (77.4) 280 (77.6) 305 (76.8)
Biological measurements, mean (SD)
 Cholesterol 20.21 (± 54.46) 20.76 (± 55.33) 19.55 (± 53.39)
 HDL 5.6 (± 16.40) 5.72 (± 16.61) 5.38 (± 16.05)
 LDL 11.4 (± 27.58) 11.66 (± 27.94) 10.97 (± 26.92)
 Triglycerides 16.61 (± 46.98) 17.1 (± 47.65) 15.98 (± 48.06)
 Last creatinine 70.51 (± 32.65) 69.81 (± 33.28) 70.33 (± 32.34)
 Last proteinuria 120.30 (± 248.67) 116.40 (± 243.04) 117.67 (± 244.37)

HDL, high-density lipoprotein; LDL, low-density lipoprotein.

Effectiveness

Change in glycated haemoglobin and fasting blood glucose from baseline to the end point

The mean HbA1c values decreased from baseline to the end point among the eligible, evaluable and overall population (Table 2). In both the eligible and evaluable populations, the mean reduction in HbA1c levels from baseline to the end of the study (16 weeks’ treatment) was 1.59% (SD ± 1.07%) and 1.60% (SD ± 1.07%), respectively, which corresponded to a 23% relative reduction. Additionally, reduction in FBG values observed in both eligible and evaluable populations at 16 weeks were significant (P < 0.001). The mean reduction in FBG from baseline to study end was 75.86 (SD ± 56.69) mg/dl and 76.26 (SD ± 57.00) mg/dl, corresponding to a 33% and 34% relative reduction in the intention-to-treat and per-protocol population, respectively.

TABLE 2

Change in mean HbA1c and FBG values from baseline to study end

Eligible population (n = 375), mean (SD) Evaluable population (n = 361), mean (SD) Overall population (n = 397), mean (SD)
HbA1c (%)
 Baseline 8.98 (± 0.96) 8.98 (± 0.96) 8.98 (± 0.96)
 Week 16 7.38 (± 0.94) 7.38 (± 0.95) 7.38 (± 0.95)
 Mean reductiona 1.59 (± 1.07) 1.60 (± 1.07) 1.60 (± 1.06)
FBG (mg/dl)
 Baseline 200.05 (± 58.87) 200.67 (± 59.21) 199.80 (± 58.26)
 Week 16 124.67 (± 27.36) 124.46 (± 27.56) 124.32 (± 27.09)
 Mean reductiona 75.86 (± 56.69) 76.26 (± 57.00) 75.53 (± 55.96)
P-value within group < 0.001 < 0.001 < 0.001

a Values are negative.

Subgroup analysis – change in glycated haemoglobin and fasting blood glucose from baseline to the end point among treatment subgroups

In the subgroup analysis of the evaluable population, there was a significant reduction (P < 0.001) in the mean HbA1c levels in both treatment subgroups (insulin glargine alone and insulin glargine with short-acting insulin) from baseline to the end of the study (16-week visit). The mean reduction in HbA1c level in the insulin glargine group was 1.62% (SD ± 1.07%) and in the insulin glargine with short-acting insulin group was 1.44% (SD ± 1.04%), corresponding to a 23.4% and 20% reduction, respectively (Figure 2). The mean difference in HbA1c reduction between the two treatment groups was 0.18% (P = 0.21), whereas the mean difference in percentage HbA1c reduction between the two groups was 3.42% (P = 0.09), neither of which was statistically significant. Similarly, there was a significant mean reduction in FBG levels within each treatment group from baseline to the 16-week visit (P < 0.001). The mean reduction in FBG in the insulin glargine group was 76.94 (SD ± 53.97) mg/dl and in the insulin glargine with short-acting insulin group was 72.05 (SD ± 68.00) mg/dl, corresponding to a 34.4% and 29.8% reduction at 16 weeks, respectively (Figure 3). The mean reduction of FBG at 16 weeks between the treatment subgroups was not statistically significant (P = 0.52).

FIGURE 2

Change in mean HbA1c levels among the treatment subgroups (insulin glargine and insulin glargine with short-acting insulin) from baseline to the 16-week visit (per-protocol population).

HMJ-441-fig2.jpg
FIGURE 3

Change in mean FBG levels among the treatment subgroups (insulin glargine and insulin glargine with short-acting insulin) from baseline to the 16-week visit (per-protocol population).

HMJ-441-fig3.jpg

Proportion of patients achieving glycated haemoglobin < 7%

A significant improvement in the percentage of patients achieving the optimum HbA1c level was observed at the end of the study. After 16 weeks’ treatment, 42.4% and 42.7% patients achieved optimum HbA1c levels (< 7%) in the eligible and evaluable populations, respectively (Table 3). Among the treatment subgroups in the evaluable population, 46.2% of patients in the insulin glargine group and 27.5% of patients in the insulin glargine with short-acting insulin group achieved HbA1c levels of <7% after 16 weeks’ treatment (P = 0.006) (Figure 4). Similar results were observed in the eligible and overall populations.

TABLE 3

Percentage of patients who achieved the optimum HbA1c level (<7%) in the eligible, evaluable and overall populations

Population Controlled, n (%) Not controlled, n (%) Total, n (%)
At first visit/4 weeks
 Overall (n = 261) 20 (7.7) 241 (92.3) 261 (100)
 Eligible (n = 251) 19 (7.6) 232 (92.4) 251 (100)
 Evaluable (n = 238) 18 (7.6) 220 (92.4) 238 (100)
At second visit/16 weeks
 Overall (n = 373) 159 (42.6) 214 (57.4) 373 (100)
 Eligible (n = 361) 153 (42.4) 208 (57.6) 361 (100)
 Evaluable (n = 361) 154 (42.7) 207 (57.3) 361 (100)

Note: Proportion is equal to success rate as none of the subjects were controlled (HbA1c < 7%) at baseline. Success rate was defined as proportion of subjects controlled at end of the study period.

FIGURE 4

Bar graph depicting HbA1c control status among study subgroups (insulin glargine and insulin glargine with short-acting insulin) at the 16-week visit (per-protocol population).

HMJ-441-fig4.jpg

Safety

Hypoglycaemia and adverse events

All enrolled patients were included for safety analyses. Hypoglycaemia was the most common AE, followed by nausea and dyspepsia. The proportion of patients with hypoglycaemia was 5.28% (21 patients) and 6.04% (24 patients) at the 4-week and 16-week visits, respectively. Of the 397 patients in the study, 24 patients experienced 41 events of hypoglycaemia during 16 weeks of treatment (Table 4), with 50% (n = 12) of them experiencing only one hypoglycaemic event during the study. Seventeen patients measured their blood glucose level during a hypoglycaemic event. The mean blood glucose level during hypoglycaemic events experienced up to week 4 was 65.68 (SD ± 12.71) mg/dl and during the whole period up to the final visit (week 16) was 64.76 (SD ± 13.39) mg/dl. One patient reported two AEs (nausea and dyspepsia) during the study. All the events were considered to be mild to moderate in severity, and there were no reports of SAEs.

TABLE 4

Proportion of patients with hypoglycaemia and total episodes among patients at risk

Overall population 4-week visit (n = 397) 16-week visit (n = 397)
Patients with hypoglycaemia episodes, n (%)
 Yes 21 (5.28) 24 (6.04)
Number of patients with events, n (%)
 One event 11 (2.7) 12 (3.0)
 Two events 8 (2.0) 10 (2.5)
 Three events 1 (0.0) 1 (0.0)
 Four events 0 (0.0) 0 (0.0)
 Five events 1 (0.0) 0 (0.0)
 Six events 0 (0.0) 1 (0.0)
 Total number of events 35 (8.8) 41 (10.3)
Reported blood glucose during hypoglycaemia events
n 38 17
 Mean (SD), mg/dl 65.68 (± 12.71) 64.76 (± 13.39)

Insulin dose

The mean dose of insulin increased from 34.11 (SD ± 18.32) IU/day at baseline to 40.89 (SD ± 18.96) IU/day at 16 weeks in the insulin glargine group and from 39.55 (SD ± 18.11) IU/day at baseline to 44.32 (SD ± 17.21) IU/day at 16 weeks in the insulin glargine with short-acting insulin group. A significant difference (P = 0.02) in mean insulin dose was observed at baseline between the two treatment subgroups; however, this difference was not significant at the end of the study (P = 0.16). In the overall population at the end of the study the mean dose of insulin glargine was 41.57 IU/day, which corresponded to 0.5 IU/kg body weight.

Discussion

The need to evaluate insulin glargine in real-life clinical settings in patients with T2DM from the Middle East prompted this study. We found significant improvement in glycaemic control in terms of HbA1c and FBG. Initiation of insulin glargine was associated with a mean reduction in HbA1c 1.60% (SD ± 1.07%) and and in FBG of 76.26 (SD ± 57.00) mg/dl, which corresponded to 23% and 34% relative reductions in the evaluable population at 16 weeks from baseline, respectively. A subgroup analysis revealed that the proportion of patients who achieved target HbA1c levels < 7% after 16 weeks was significantly higher in the group treated only with insulin glargine and OAD than in the group that also received short-acting insulin (46.2% vs. 27.5%; P = 0.006). Hypoglycaemic episodes were reported by 21 patients (5.28%) at week 4 and by 24 patients (6.04%) at week 16. All AEs were mild to moderate, showing that insulin glargine was well tolerated.

Evidence from several studies indicates that switching patients with T2DM from premixed insulin to insulin glargine is safe, effective and convenient, and is associated with significant improvement in glycaemic control.2225,29 A 12-week observational study involving 5045 patients with T2DM inadequately controlled with pre-mixed insulin showed significant improvements in FBG (P ≤ 0.001) and HbA1c (P ≤ 0.001) when patients were switched to insulin glargine plus OADs.23 Likewise, in a randomized study comparing pre-mixed insulin with basal/bolus therapy using insulin glargine in T2DM patients, the difference in HbA1c change after 6 months of treatment was 0.22% in favour of the glargine-based regimen.30 Although the reductions in HbA1c or FBG were not compared with any pre-mixed insulin-based therapy in this study, the general trend of clinically significant beneficial glycaemic changes in response to glargine therapy with OADs is confirmed by our results.

In this study 42.7% of the evaluable population achieved the optimum HbA1c level (< 7%) at 16 weeks. This is consistent with a previous randomized study which reported that patients in the basal bolus group were more likely than those in the pre-mixed insulin group to achieve HbA1c < 7.0% [68 participants (46.6%) vs. 43 participants (27.9%); P = 0.0004].18 However, in a previous observational study from China, only 19.5% of patients with T2DM treated with insulin glargine achieved HbA1c < 7%, compared with 42.3%.22 Similarly, in another observational study by Hammer and Klinge,23 73.9% patients were shown to achieve a target HbA1c of < 7.5%. In view of the results from previous studies, the findings from our study might become particularly important as more patients achieved the stringent ADA target HbA1c level of < 7%, pointing to better effectiveness of insulin glargine in this population.

In our study, in patients who were not well controlled on glargine plus OADs, addition of short-acting insulin was associated with improved glycaemic control. However, it should be noted that patients entitled to short-acting insulin along with insulin glargine plus OADs had higher baseline HbA1c values than those receiving only insulin glargine plus OADs and a similar mean reduction in HbA1c. This indicates that the addition of short-acting insulin may be considered in patients with T2DM only if clinically indicated to provide higher glycaemic control. In other words, in patients in whom insulin glargine is initiated early enough, good glycaemic control is seen, thus avoiding worsening of HbA1c levels and delaying the addition of bolus insulin. Furthermore, the GINGER study demonstrated significantly superior glycaemic control with an intensified basal bolus regimen using glargine/glulisine compared with pre-mixed insulin therapy in a population with long-standing insulin-treated T2DM, without an increase in the rates of hypoglycaemia.18 In our study patients uncontrolled on pre-mixed insulin benefited from an insulin glargine-based therapy with the addition of a single dose of short-acting insulin. Thus, the use of insulin glargine along with a single injection of short-acting insulin seems preferable to pre-mixed insulin.

Tight glycaemic control is commonly associated with an increased risk of hypoglycaemia, representing a major barrier for initiation of insulin therapy.8,3133 In our study, despite a stringent glycaemic target of HbA1c < 7%, only 6.04% of patients had episodes of hypoglycaemia, with 50% experiencing a single episode, indicating that glargine-based regimens is safe with a low risk of hypoglycaemia. Evidence from several studies, including LAPTOP,34 APOLLO35 and the AT.LANTUS study,25,36 suggests that a regimen composed of once-daily insulin glargine plus OADs is associated with better glycaemic control and a lower risk of hypoglycaemia.16,24,3539

At the end of the study, the mean dose of insulin glargine was 41.57  IU/day, which corresponded to 0.5  IU/kg body weight. The insulin dose was slightly higher than in previous observational studies, in which the daily dose of insulin glargine was optimized to about 0.4  IU/kg body weight.22,23,40 This suggests that Arabic-speaking patients in whom glycaemic control using pre-mixed insulin is unsatisfactory may require a slightly higher daily dose of insulin glargine to achieve optimal glycaemic control. However, when compared with conventional or pre-mixed insulin therapy, the insulin glargine regimen has been associated with significantly lower insulin doses and fewer blood glucose test strips,41 and has been projected to be a cost-effective option42 compared with pre-mixed insulin in patients with poorly controlled T2DM on OADs.

The results from this study are limited by the fact that it is an observational study and may not provide as strong a level of evidence as that of randomized controlled trials. Second, the number of patients included for analysis was relatively small and the analysis of clinical data were conducted over a relatively short study period. Moreover, the addition of OADs to insulin glargine or insulin glargine with short-acting insulin was decided solely by the investigator, and the extent to which this study design may have confounded the results is unclear.

Conclusion

In conclusion, this observational study demonstrated significant overall improvements in HbA1c and FBG when initiated on insulin glargine in patients with inadequately controlled T2DM on pre-mixed insulin. Furthermore, addition of short-acting insulin to insulin glargine increased the likelihood of attaining HbA1c goals (HbA1c < 7%), and appeared to be safe and well tolerated.

Acknowledgements

The authors acknowledge Jeevan Scientific Technology Limited (Hyderabad, India) and Anahita Gouri of Sanofi (India) for providing writing and editing assistance in developing this manuscript.

Funding

This study was funded by Sanofi Gulf.

Conflict of interest

Dr Ghaida Kaddaha received honorarium fees from Sanofi as principal investigator for this study. He has also received consulting and lecture fees from Sanofi, Novo Nordisk, AstraZeneca, Novartis, Eli Lilly and Janssen Pharmaceuticals.

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