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J Indon Med Assoc, Volum: 61, Nomor: 11, November 2011 429

Glycemic Control inSwitching Insulin-based Regimen Among

Type 2 Diabetic Patients

Pradana Soewondo, Imam Subektion behalf of INTERBASE Study Group

Department of Internal Medicine, Faculty of Medicine Universitas Indonesia/Dr. Cipto Mangunkusumo Hospital, Jakarta

Abstract: Appropriate diet and physical activity, maintaining a healthy body weight and propercontrol of diabetes using oral anti diabetic (OAD) in people with diabetes type 2 will helpreduce its complications. However, some advance diabetic cases need insulin-based regimen toaggressively lower blood glucose level. Local data was insufficient to determine whether type 2diabetes patients on insulin were indeed attaining glycemia goals. The aim of this study was toassess the clinical response of type 2 diabetic patients who were switched to another insulinregimen to achieve glycemic control. The study was performed as a non-interventional prospec-tive disease registry that mirror real life management of these subjects after a 3 month follow up.To assess the clinical response, we performed measurement of fasting blood glucose level, HbA1c,waist circumference and body weight. One hundred and fifteen type 2 diabetes patients whowere already on insulin therapy with unsatisfactory control of glycaemia parameters wereadmitted in this study of an actual clinical setting. Only 93 cases have been examined in a 3month follow up. Premix, Short-acting and Intermediate-acting insulin were the most popularinsulin-based regimens that previously been prescribed, while basal analogue insulin is themost common regimen for switching therapy. The newly prescribed insulin-based regimen showedsignificant reduction of important glycaemia parameters such as fasting blood glucose level andHbA1c. Serum blood glucose was decreased 61.76 mg/dL (p

J Indon Med Assoc, Volum: 61, Nomor: 11, November 2011430

Kontrol Glikemik pada Penderita DM Tipe 2dengan Perubahan Rejimen Insulin

Pradana Soewondo, Imam Subekti,atas nama INTERBASE Study Group

Departemen Ilmu Penyakit Dalam, Fakultas Kedokteran Universitas Indonesia/Rumah Sakit Umum Pusat Dr. Cipto Mangunkusumo, Jakarta

Abstrak: Kontrol diabetes secara rutin dengan mengatur diet dan aktivitas fisik, menjaga beratbadan ideal dan konsumsi obat hipoglikemia oral (OHO) diharapkan dapat menurunkankomplikasi kronik Diabetes Melitus tipe 2. Meskipun demikian, sejumlah kasus diabetes yanglanjut memerlukan terapi insulin untuk menurunkan kadar glukosa darah secara agresif. Datapenelitian yang ada di Indonesia masih kurang mencukupi untuk menggambarkan pencapaiantarget glikemik pada pasien DM tipe 2 yang menggunakan insulin. Tujuan penelitian ini adalahmenilai respons klinis pasien DM tipe 2 dengan perubahan rejimen insulin untuk pencapaiantarget glikemik. Penelitian ini menggunakan desain studi registri non-interventional, prospektif,mencerminkan penanganan DM tipe 2 sehari-hari setelah terapi selama 3 bulan. Untuk menilairespons klinis, dilakukan pemeriksaan kadar glukosa darah puasa, HbA1c, lingkar pinggangdan berat badan. Seratus lima belas pasien DM tipe 2 yang telah menggunakan insulin namunbelum mencapai kontrol glikemik kemudian diubah jenis terapi insulinnya selama 3 bulan dalamkondisi klinis sehari-hari. Hanya 93 kasus yang dapat dinilai selama 3 bulan terapi. Insulinpremix, kerja pendek dan kerja menengah merupakan jenis insulin yang terbanyak digunakansebelumnya, sedangkan insulin basal analog adalah insulin terbanyak yang digunakan dalamperubahan terapi. Perubahan jenis insulin yang baru menunjukkan penurunan parameter glikemikyang bermakna, yakni kadar glukosa darah puasa dan HbA1c. Penurunan glukosa darah mencapai61,76 mg/dL (p

Glycemic Control in Switching Insulin-based Regimen Among Type 2 Diabetic Patients

J Indon Med Assoc, Volum: 61, Nomor: 11, November 2011 431

MethodsThis study was performed as a non-interventional pro-

spective disease registry that mirror real life management ofthese subjects (purely for observational study). Nineteenstudy centers from four provinces in Indonesia (Jakarta,West Java, East Java and Bali) have reported 115 type 2diabetic patients who were currently receiving insulin treat-ment but still had uncontrolled glycemia parameter (HbA1c> 8%, data from the DiabCare Asia 2008 study demonstratesthe mean of HbA1c achieved was 8.1%), whose physicianshad decided to change the current insulin regimen to a newinsulin regimen due to any reason, and were willing to signa informed consent form.

All Data Collection Forms (DCFs) were verified for ex-istence and eligibility of patients, and for the presence ofinformed consent. A Source Data Verification was performedin 63% of the sites.

The quantitative variables were compared by an analy-sis of the variance and Students paired t-test (for param-eters measured before and after the treatment period). Allstatistical tests have been performed using 2-tailed tests at5% level of significance or with adjustment if needed.Results

The diabetic cases were equally distributed among maleand female patients with an average age of 54 years (SD =8.8 years). The majority of cases belonged to 50 60 yearsage group. The average body mass index was 24.1 kg/mand the waist circumference was 88.3 cm. The HbA1c andfasting blood glucose level at baseline were particularly high(Table 1).

As all of the cases are in unsatisfactory state of glycae-mia control, most of them suffered from diabetic complica-tions. Neuropathy is the most common complication with67.8% of subject show neurological signs. The second most

Table 1. Characteristic of Subjects

Variable N (%) Mean or Median

Gender (n=115)Male 56 (48.7)Female 59 (51.3)

Age (n=114) 54.0 +/- 8.861 + yrs 18 (15.8)50 - 60 yrs 59 (51.8)< 50 yrs 37 (32.5)

Education (n=112)Low 28 (25.0)Middle 56 (50.0)High 28 (25.0)

Previous insulin(s) (n=115)Rapid-acting 10 (8.7)Short-acting 40 (34.8)Intermediate-acting 32 (27.8)Basal analogue 9 (7.8)Premix 31 (27.0)

Previous OAD(s) (n=115)Glimepiride 21 (18.3)Acarbose 22 (19.1)Metformin 63 (54.8)Gliquidone 7 (6.1)Glibenclamide 14 (12.2)Gliclazide 30 (26.1)Glibenclamide/Metformin 5 (4.3)Other 3 (2.6)

Type 2 diabetes history (yrs, n=93) 6.1 +/- 4.9Body Mass Index (kg/m, n=115) 24.1 +/- 4.4Waist circumference (cm, n=106) 88.3 +/- 12.3Systolic blood pressure (mmHg, n=115) 132.5 +/- 18.0Diastolic blood pressure (mmHg, n=115) 81.9 +/- 8.8HbA1c (%, n=115) 10.0 +/- 1.8Fasting blood glucose (mg/dl, n=108) 223 (43-501)

0 10 20 30 40 50 60 70 80

P e r c e nt

Dyslipidemia

Hypert ension

Vascular

Nephropat hy

Neuropat hy

Ret inopat hy

common complication is retinopathy with 30.7%, followedby vascular diseases and nephropathy with 26.1% and 23.5%respectively. Dislipidemia and hypertension are the two con-comitant conditions of diabetes. More than 71% of cases

Figure 1. Clinical Signs of Diabetics Complication



Table 2. Means and Standard Devisition of Daily Does of the Previous and Current Insulin Regimen

Type of Insulin Previous Insulin Current InsulinNumber Mean S D Min Max Number Mean S D Min Max

Long-acting insulin 6 22.7 12.8 8 42 80 18.1 9.5 8 40Intermediate insulin 26 16.2 7.8 8 40 NilShort acting insulin 33 30.2 16.1 6 75 2 60 0 60 80Rapid acting insulin 9 30.7 12.2 18 60 12 21.8 13 6 48Premix insulin 25 22.5 10.4 8 50 12 22.8 5.2 14 34

0 10 20 30 40 50 60 70 80 90

Percent

Rapid-act ing

Basal analogue

Intermediate-act ing

Short-act ing

Premix

Pre New

Figure 2. Previous and Newly Prescribed Insulin-based Regimens

also suffered from dislipidemia and almost 48% have highblood pressure (figure 1).

The most common prescribed insulin-based regimensare short-acting (34%), followed by intermediate-acting(27.8%) and premix (27%). Basal analogue (7.8%) and rapid-acting (8.7%) were rarely prescribed as first line insulin-basedregimens. The daily dose administration of short- and rapid-acting insulin was higher than other regimens (table 2). Know-ing that these previously prescribed insulin regimens showedunsatisfactory response of glycemia control, the doctorsagreed to switch to new insulin regimen.

The newly prescribed regimens are dominated withbasal analogue (85.2%) and only few patients were givenpremix (13%) or rapid-acting Insulin (9.6%) (figure 2). Thedaily dose administration of short-acting insulin was thehighest among insulin regimens (Table 2). After therapy waschanged, patients received either insulin alone or combina-tion with OAD, depending on the new treatment. Approxi-mately 20% of patients with basal analogue insulin receivedonly basal insulin during the study, while others receivedcombination therapy with OAD(s) (table 3). These patientswere followed up after a therapeutic period of 3 months.

Only 93 patients returned to the study centers and could beexamined.

After a 3 month period using newly prescribed insulin-based regimen, there are significant improvements of some

Table 3. Distribution of Subjects According to Current Insu-lin Regimen and Concomitant Oral Therapy (n=93)

Concomitant Current insulin regimen TotalOral Therapy Glargine Glul is ine Premix

Glimepiride 11 0 0 11Arcabose 10 0 0 10Metformin 19 1 6 26Gliquidone 8 1 0 9Glibenclamide 3 0 2 5Pioglitazone 1 0 0 1Glibenclamide/ 5 1 0 6

MetforminGliclazide 4 0 3 7Glipizide 1 0 0 1No concomitant 16 0 1 17oral therapy

Total 78 3 12 93



433

important glycemia parameters. Level of HbA1c decreasedfrom 9.83+1.71% to 8.44+1.85% (p



nificantly with an average of 0.70 cm. There is an interestingphenomenon that almost 43% of subject showed good re-sponse in reducing body weight, but in overall there was anaverage of 0.26 kg weight gain experienced by type 2 diabe-tes patients at the 3 month follow up visit, though it was notstatistically significant. The good response of important gly-caemia parameters to the changing of insulin-based regimenmight reflects the probability of treatment saturation for spe-cific regimen due to complex biological processes. The satu-rated regimen needs to be replaced with other regimen toenable better response in type 2 diabetes patient.

ConclusionIt was concluded that despite the prescription of insu-

lin-based regimens combined with OAD for type 2 diabetespatients, there were still cases of unsatisfactory glycemiccontrol that need medification of insulin regimen. Medificationof insulin-based regimen gave better result for the type 2diabetes patients.

AcknowledgementThe authors are especially grateful to all investigators

who have participated in INTERBASE study: Dr. SulistiawatyOhnio, SpPD, Dr. Maxwadi Maas, SpPD, Dr. Eliana Taufik,SpPD, Dr. Asep Saepul Rohmat, SpPD, Dr. Arief Wibowo,SpPD, Dr. Anton Cahaya, Dr. Sutji Muljati, Dr. Mery Harita,Dr. Hadi Sunaryo, SpPD, Dr. Maria Meilitasari Harlim, SpPD,Dr. R. Eka, SpPD, Dr. Nunik K.Kartikawati, Dr. Ishak S.Dinata,SpPD, Dr. G. Wisito, SpPD, Dr. Agatha Maharani, SpPD, Dr.Johannes Lusida, SpPD, Dr. Ratna Saraswati, SpPD, Dr. J. M.Maitriya, SpPD

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