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Journal of Endocrinology & Metabolism

Original Article

Volume 5, Number 6, December 2015, pages 333-336

Observational Study of the Use of Insulin Glargine as Basal Therapy in Patients With Type 2 Diabetes Mellitus in Morocco

Type 2 diabetes mellitus (T2DM) is the most common metabolic disorder worldwide and results from the combination of abnormal secretion and action of insulin [1]. Achieving and maintaining a target glycated hemoglobin (HbA1c) level of < 7% in patients with T2DM reduces the risk of developing diabetes complications, particularly microvascular complications such as nephropathy, retinopathy and neuropathy [2]. However, prospective studies have shown that many patients in routine medical practice do not achieve optimal glycemic control [3-5]. International guidelines emphasize the importance of early initiation of T2DM therapies, particularly the initiation of insulin therapy, in patients who are poorly controlled with other antidiabetic medications, to modify the course of hyperglycemia and to prevent or delay the development of long-term complications [2, 6]. Assessing the real-life use of therapeutic alternatives to standard insulin regimens is extremely important.

In Morocco, few data are available on the efficacy and safety of insulin therapy in patients with T2DM. The aim of this prospective, observational study was to assess the efficacy and safety of long-acting insulin glargine (Lantus^®, Sanofi) in T2DM patients who were inadequately controlled with oral antidiabetic drug (OAD) therapies or other types of insulin.

This national, multicenter, observational study took place between May 2010 and June 2011. A total of 50 randomly selected endocrinologists-diabetologists across Morocco were asked to participate in the study. Patients with T2DM were enrolled if they fulfilled the following inclusion criteria: adults (male or female) aged ≥ 18 years with uncontrolled T2DM, HbA1c between 7.5% and 10.5% despite antidiabetic treatment in addition to lifestyle and dietary measures conducted for at least 6 months, and basal insulin therapy initiated. Participating physicians recruited the first 10 patients meeting all inclusion criteria. All eligible patients gave their signed informed consent to take part in the study.

Patients aged < 18 years, those with known hypersensitivity to glargine, pregnant or breastfeeding women were excluded from the study. Taking into account a 25% expected control rate, 4% precision and 20% dropout, the calculated sample size was 495 patients.

Only patients given basal therapy with insulin glargine were included in the analysis. Patients were treated with insulin glargine (100 IU/mL solution for subcutaneous injection) at the physician’s discretion and according to local Summary of Product Characteristics (SmPC) requirements. According to local SmPC, insulin glargine is administrated subcutaneously once a day at any time but at the same time each day. The dosage and timing of insulin glargine doses is titrated and individually adjusted to achieve fasting blood glucose (FBG) levels of < 130 mg/dL according to the ADA/EASD consensus algorithm published in January 2009 [6].

Data for each patient were collected by the participating physicians using a standardized questionnaire at each visit. All patients had three visits: an initial inclusion (baseline) visit and two follow-up visits at week 12 and week 26 after inclusion. The total duration of the study for each patient was 6 months.

The following data were collected at baseline: age, sex, weight, height, waist circumference, duration of diabetes, previous treatments, duration of insulin therapy, doses of insulin, FBG and HbA1c level; and at the two follow-up visits: weight, waist circumference, HbA1c level, FBG, dose of insulin glargine administered, addition of another insulin dose, oral medications and their doses (if applicable), hypoglycemic events and their characteristics (symptomatic, severely symptomatic, and diurnal/nocturnal).

The primary objective was to describe the proportion of T2DM patients with HbA1c < 7% after 6 months of real-life treatment with insulin glargine. The secondary objective was to describe number of hypoglycemic events.

A descriptive analysis was performed on the socio-demographic, clinical and therapeutic characteristics of the patients. Classic tests for paired samples (Student’s t-test and MacNemar test) were used to compare qualitative and quantitative variables between baseline and each visit. A P value of < 0.05 was considered statistically significant.

SPSS version 17.0 was used for all statistical analyses.

A total of 50 centers across Morocco took part in the study and 498 patients were enrolled. Data were available for 497 (99.8%) of these patients. Mean age was 57.5 ± 10.3 years, 55.5% of the patients were female and mean duration of diabetes was 9.8 ± 6.1 years (Table 1). Using the WHO body mass index (BMI) classification, 74.7% of patients were overweight or obese.

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Table 1. Characteristics of the Study Population at Inclusion (Baseline)

At baseline, 388 patients (78.1%) were being treated with OADs alone and 109 (21.9%) were receiving insulin other than insulin glargine (61 on insulin + OADs and 48 on insulin alone). Among the 109 patients receiving insulin, 53 (48.6%) patients were on a basal regimen, 11 (10.1%) were on a basal + prandial regimen and 39 (35.8%) were being treated with premixed insulins. Data were not available for six patients. All patients were started on a basal insulin glargine regimen at a mean dose of 17.2 ± 6.8 IU/day.

The treatment changes in these patients over the 6-month follow-up period are shown in Table 2. OAD treatment was changed in 31.4% of patients at visit 2 and in 12.6% of patients at visit 3. Insulin glargine doses were changed in 82.2% of patients at visit 2 and in 47.9% at visit 3. The mean daily dose of insulin glargine was increased significantly (P < 0.001) during follow-up (17.2 ± 6.8 IU at baseline, 22.5 ± 6.8 IU at visit 2 and 24.4 ± 7.3 IU at visit 3). Rapid insulin was added to the basal regimen in 9.3% of patients at visit 2 and in 7.0% of patients at visit 3.

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Table 2. Changes in Antidiabetic Treatments Over the 6-Month Study Period

The evolution of HbA1c levels after initiation of insulin glargine in insulin-naive patients or continuing/changing insulin therapy to insulin glargine in patients previously treated with insulin is shown in Table 3. Regarding the primary endpoint, 11.5% (55/477) of patients reached the target HbA1c of < 7% after 12 weeks of treatment and 32.0% (149/465) after 26 weeks. Mean HbA1c decreased significantly from 9.37±1.14% to 8.08±1.03% (P < 0.001) after 12 weeks of treatment with insulin glargine and to 7.43±0.87% (P < 0.001) after 26 weeks. Overall, mean HbA1c was reduced by 1.9±1.2% from baseline to the last visit at week 26 (P < 0.001). Mean FBG also decreased significantly from 237.5 ± 66.9 mg/dL at baseline to 129.5 ± 35.1 mg/dL at week 26 (P < 0.001), which represented an overall reduction of 108.1 ± 69.8 mg/dL.

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Table 3. Evolution of Efficacy Outcome Measures During the 6-Month Study Period

A total of 471 patients were included in the safety analysis. Safety data were missing for the other 27 patients. Forty-six patients (9.8%) reported episodes of hypoglycemia between inclusion and visit 2 and 55 (12%) between visit 2 and visit 3. Diurnal and nocturnal hypoglycemia episodes were reported by 33 and 21 patients respectively at visit 2 and 37 and 28 patients respectively at visit 3. Symptomatic hypoglycemia was reported by 35 patients at visit 2 and 38 patients at visit 3. Three patients reported severe episodes of hypoglycemia at visit 3 but no severe hypoglycemia was reported during visit 2. The outcome of these three patients was not documented. No adverse event other than hypoglycemia was reported during the study period.

The mean body weight of the patients increased significantly from 76.1 ± 12.3 kg at inclusion to 77.2 ± 11.8 kg at visit 3, an increase of 1.3 ± 3.8 kg (P < 0.001).

This observational study reports the efficacy and safety of insulin glargine in T2DM patients in Morocco who were inadequately controlled with other antidiabetic treatments and required optimal basal insulin therapy. The results show that, in a real-life setting, a basal regimen with insulin glargine is associated with a significant reduction in mean HbA1c levels and in mean FBG.

These results confirm those observed in clinical studies with insulin glargine conducted in other countries [7]. In the present study, treatment of T2DM patients with insulin glargine for 6 months was associated with a reduction in HbA1c of 1.9±1.2% and a reduction in FBG of 108.1 ± 69.8 mg/dL. The percentage of patients with controlled diabetes (HbA1c ≤ 7%) was 11.5% at visit 2 (3 months) and 32.0% at visit 3 (6 months) after the initiation of insulin glargine. A recent real-life study carried out in France [8] reported that the mean HbA1c level decreased from 8.3% at baseline to 7.8% a month after the initiation of insulin glargine and to 7.5% at the end of follow-up (12 months). The proportion of patients with HbA1c < 7% increased from 19.9% to 33.4% after the initiation of insulin glargine in patients previously treated with insulin and from 13.9% to 39.1% in insulin-naive patients [8]. Similar results were reported in other recent observational studies [9-11]. The mean daily dose of insulin glargine at 6 months was 24.4 ± 7.3 IU. This dose is inferior to the doses used in western countries. Further studies may be needed to explain this difference.

The safety of insulin glargine has been assessed in several studies in patients with T2DM, usually in comparison with NPH insulin [8-13]. In general, phase III clinical studies have shown a decreased incidence of hypoglycemia (including severe hypoglycemia requiring the intervention of a third person), especially nocturnal hypoglycemia. In the present study, 12% of patients reported hypoglycemic episodes during the follow-up period but only three patients (0.6%) reported severe episodes of hypoglycemia after 6 months of treatment. The outcome of these three patients is not known. Insulin glargine treatment is often associated with a minor gain in body weight [8, 14]. In the present study, the mean weight gain was 1.3 kg during the 6-month follow-up period. This compares with 0.8 kg in the ATLANTUS study [14] and 0.7 kg in the French study [8].

In conclusion, this observational study conducted in Morocco shows that, in a real-life setting, a basal regimen with insulin glargine significantly improves glycemic control in patients with T2DM who are poorly controlled with OAD medications or other insulin regimens, with an acceptable hypoglycemia profile.

Acknowledgement

The authors thank Newmed Publishing Services, France, for medical writing services.

Grant Support

Sanofi Maroc provided funding for the collection of registry data and for medical writing services.

Conflicts of Interest

A.C. and H.I. received grant support and/or served as consultants for Sanofi, Eli Lilly, Novo Nordisk, Servier, MSD, Abbott, Novartis and AstraZeneca. Y.E. and C.N. declare no conflicts of interest. M.S. is an employee of Sanofi Maroc.

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Journal of Endocrinology and Metabolism is published by Elmer Press Inc.