Internal Medicine Section
DOI: 10.7860/JCDR/2017/27649.10214
Original Article
Short Term Efficacy and Safety of Insulin Glargine in Type 2 Diabetes Inadequately Controlled with Single or Two Oral Agents: A Prospective, Open Label Study
Ajay Aggarwal1, Roopak Wadhwa2
ABSTRACT Introduction: Basal insulin is among the second line treatment options for Type 2 Diabetes Mellitus (T2DM). Efficacy and safety of basal insulin in patients of T2DM, uncontrolled with Oral Antidiabetic Agents (OAAs) remains understudied in the Indian setting. Aim: To assess the efficacy and safety of insulin glargine in patients with T2DM who have uncontrolled glycaemic levels despite single or two OAAs therapy. Materials and Methods: In this prospective, open label study, T2DM patients above 40 years of age, having inadequate glycaemic control [Glycosylated Haemoglobin (HbA1c) above 8% and/or fasting glucose level of 140 mg/dl and above] with single or two OAAs over three consecutive months were included. Dosing of insulin glargine was adjusted as per Fasting Blood Glucose (FBG) and Post Prandial Blood Glucose (PPBG)
levels. Patients were followed for 12 weeks and data was analysed by comparing 12th week findings to baseline values. Results: In 40 cases included in final analysis, mean age was 56.35 ± 6.77 years, 52.5% were females and mean body mass index was 26.96 ± 4.59 kg/m2. Compared to baseline, significant reduction in HbA1c, FBG and PPBG blood glucose (all p0.05) and diastolic (p0.05). Overall, 14 symptomatic hypoglycaemia events were observed with none being severe. Conclusion: Short term administration of insulin glargine is effective in reducing glycaemia and is safe with lower rates of severe hypoglycaemia. It can be considered in patients with uncontrolled T2DM on mono- or two- OAAs treatment.
Keywords: Basal insulin, Glycaemia, Hypoglycaemia, Uncontrolled diabetes
Introduction Type 2 Diabetes Mellitus (T2DM) is characterized by progressive loss of beta cells of pancreas leading to failure of anti hyperglycaemia therapy. With increasing duration of T2DM, insulin therapy may become essential in majority of the patients [1]. Estimates from the year 2015 suggest that there are 69.2 million diabetic patients in India and this number is projected to increase to 123.5 million by the year 2040 [2]. T2DM is the major form of DM in Indians accounting for 90% of total diabetes burden. Besides being significant in prevalence, diabetes also has significant socioeconomic impact [3]. Reducing hyperglycaemic burden with achievement of glycaemic targets is known to reduce microvascular and macrovascular complications of diabetes [4,5]. Thus, the control of glycaemia is essential to reduce disease related and social complications arising due to T2DM. Insulin is the most potent hypoglycaemic agent that has undoubted place in the management of uncontrolled T2DM [1]. As an add-on to the OAAs, basal insulin is the recommended as initial insulin [6]. In Indian patients with T2DM, insulin therapy has been found effective in improving glycaemic control and quality of life [7]. Insulin glargine, one of the initial basal insulins, administered as once-a-day therapy is found to have equivalent efficacy as compared to the repeated short-acting insulin with advantages of low hypoglycaemia, better patient satisfaction and fewer injections [8]. Also, basal insulin therapy given for six months duration has been reported to provide better long term glycaemia control compared to OAAs [9]. Insulin glargine is associated with lower hypoglycaemia risks than other Journal of Clinical and Diagnostic Research. 2017 Jul, Vol-11(7): OC21-OC24
insulin regimens [10]. Given these advantages with basal insulin glargine, we studied its efficacy and safety in patients with T2DM, uncontrolled on single or two OAAs.
MATERIALS AND METHODS The present prospective, open label, observational study was conducted at a Diabetes unit of the Internal Medicine Department of a Tertiary Care Hospital in New Delhi, India. Study duration was two years i.e., between December 2012 to December 2014. Study protocol was approved by Institutional Ethical Committee. Informed consent was obtained from all patients before entry in to the study. Patients of uncontrolled T2DM were recruited. Inclusion criteria were adult patients aged above 40 years, inadequate glycaemic control with monotherapy or two drug combination therapy for three consecutive months as suggested by HbA1c of 8% and above on background of dietary and lifestyle measures, FBG above 140 mg/dl. Excluded were those patients with triple oral drug therapy, pregnant women, those receiving steroid, known history of allergic reaction to insulin, renal dysfunction (serum creatinine >1.5 mg/dl]. One week run-in period was allowed for the patients to understand the study, follow the instructions clearly and to assess their adherence to the study. All patients were advised similar level of dietary and lifestyle restrictions. Patients were started with 10 units of insulin glargine at bed time as an add-on to the current oral hypoglycaemic treatment. In this 12-week study, each patient was followed weekly for insulin dose titration based on FBG and PPBG. At baseline and at each visit, 21
Ajay Aggarwal and Roopak Wadhwa, Insulin Glargine in Inadequately Controlled Type 2 Diabetes
weight, blood pressure, FBG and PPBG was recorded. HbA1c (%) was evaluated at baseline and at the end of 12-week period. All the biochemical investigations were carried out at hospital central laboratory. Blood glucose estimation was performed with glucose oxidase-peroxidase method. Glycosylated haemoglobin was estimated by cation exchange resin method using glycolhaemoglobin reagent set. As patients were initiated for the first time with insulin treatment, they were followed weekly to detect early changes in glycaemia and to detect incidence of hypoglycaemia. At each visit, detailed clinical examination, assessment of patient diaries for hypoglycaemia episodes, and blood sugar (FBG and PPBG) were performed. Patients unwilling to follow up weekly were excluded. All patients were reminded telephonically to maintain adherence to study visits. Patients who did not return for follow up visit even after telephonic reminders within two days of scheduled visits were excluded from the study. Patients were asked to maintain a diary to record any events related to therapy. Patients were educated on symptoms of hypoglycaemia at baseline and were asked to record such symptoms with their relation to time and dosing of insulin in patient diaries. For each patient, adherence to continued lifestyle modification was ensured at each visit. Efficacy was assessed by glycaemic changes from baseline to 12 weeks in HbA1c, FBG and PPBG and achievement of goal HbA1c of
DOI: 10.7860/JCDR/2017/27649.10214
Original Article
Short Term Efficacy and Safety of Insulin Glargine in Type 2 Diabetes Inadequately Controlled with Single or Two Oral Agents: A Prospective, Open Label Study
Ajay Aggarwal1, Roopak Wadhwa2
ABSTRACT Introduction: Basal insulin is among the second line treatment options for Type 2 Diabetes Mellitus (T2DM). Efficacy and safety of basal insulin in patients of T2DM, uncontrolled with Oral Antidiabetic Agents (OAAs) remains understudied in the Indian setting. Aim: To assess the efficacy and safety of insulin glargine in patients with T2DM who have uncontrolled glycaemic levels despite single or two OAAs therapy. Materials and Methods: In this prospective, open label study, T2DM patients above 40 years of age, having inadequate glycaemic control [Glycosylated Haemoglobin (HbA1c) above 8% and/or fasting glucose level of 140 mg/dl and above] with single or two OAAs over three consecutive months were included. Dosing of insulin glargine was adjusted as per Fasting Blood Glucose (FBG) and Post Prandial Blood Glucose (PPBG)
levels. Patients were followed for 12 weeks and data was analysed by comparing 12th week findings to baseline values. Results: In 40 cases included in final analysis, mean age was 56.35 ± 6.77 years, 52.5% were females and mean body mass index was 26.96 ± 4.59 kg/m2. Compared to baseline, significant reduction in HbA1c, FBG and PPBG blood glucose (all p0.05) and diastolic (p0.05). Overall, 14 symptomatic hypoglycaemia events were observed with none being severe. Conclusion: Short term administration of insulin glargine is effective in reducing glycaemia and is safe with lower rates of severe hypoglycaemia. It can be considered in patients with uncontrolled T2DM on mono- or two- OAAs treatment.
Keywords: Basal insulin, Glycaemia, Hypoglycaemia, Uncontrolled diabetes
Introduction Type 2 Diabetes Mellitus (T2DM) is characterized by progressive loss of beta cells of pancreas leading to failure of anti hyperglycaemia therapy. With increasing duration of T2DM, insulin therapy may become essential in majority of the patients [1]. Estimates from the year 2015 suggest that there are 69.2 million diabetic patients in India and this number is projected to increase to 123.5 million by the year 2040 [2]. T2DM is the major form of DM in Indians accounting for 90% of total diabetes burden. Besides being significant in prevalence, diabetes also has significant socioeconomic impact [3]. Reducing hyperglycaemic burden with achievement of glycaemic targets is known to reduce microvascular and macrovascular complications of diabetes [4,5]. Thus, the control of glycaemia is essential to reduce disease related and social complications arising due to T2DM. Insulin is the most potent hypoglycaemic agent that has undoubted place in the management of uncontrolled T2DM [1]. As an add-on to the OAAs, basal insulin is the recommended as initial insulin [6]. In Indian patients with T2DM, insulin therapy has been found effective in improving glycaemic control and quality of life [7]. Insulin glargine, one of the initial basal insulins, administered as once-a-day therapy is found to have equivalent efficacy as compared to the repeated short-acting insulin with advantages of low hypoglycaemia, better patient satisfaction and fewer injections [8]. Also, basal insulin therapy given for six months duration has been reported to provide better long term glycaemia control compared to OAAs [9]. Insulin glargine is associated with lower hypoglycaemia risks than other Journal of Clinical and Diagnostic Research. 2017 Jul, Vol-11(7): OC21-OC24
insulin regimens [10]. Given these advantages with basal insulin glargine, we studied its efficacy and safety in patients with T2DM, uncontrolled on single or two OAAs.
MATERIALS AND METHODS The present prospective, open label, observational study was conducted at a Diabetes unit of the Internal Medicine Department of a Tertiary Care Hospital in New Delhi, India. Study duration was two years i.e., between December 2012 to December 2014. Study protocol was approved by Institutional Ethical Committee. Informed consent was obtained from all patients before entry in to the study. Patients of uncontrolled T2DM were recruited. Inclusion criteria were adult patients aged above 40 years, inadequate glycaemic control with monotherapy or two drug combination therapy for three consecutive months as suggested by HbA1c of 8% and above on background of dietary and lifestyle measures, FBG above 140 mg/dl. Excluded were those patients with triple oral drug therapy, pregnant women, those receiving steroid, known history of allergic reaction to insulin, renal dysfunction (serum creatinine >1.5 mg/dl]. One week run-in period was allowed for the patients to understand the study, follow the instructions clearly and to assess their adherence to the study. All patients were advised similar level of dietary and lifestyle restrictions. Patients were started with 10 units of insulin glargine at bed time as an add-on to the current oral hypoglycaemic treatment. In this 12-week study, each patient was followed weekly for insulin dose titration based on FBG and PPBG. At baseline and at each visit, 21
Ajay Aggarwal and Roopak Wadhwa, Insulin Glargine in Inadequately Controlled Type 2 Diabetes
weight, blood pressure, FBG and PPBG was recorded. HbA1c (%) was evaluated at baseline and at the end of 12-week period. All the biochemical investigations were carried out at hospital central laboratory. Blood glucose estimation was performed with glucose oxidase-peroxidase method. Glycosylated haemoglobin was estimated by cation exchange resin method using glycolhaemoglobin reagent set. As patients were initiated for the first time with insulin treatment, they were followed weekly to detect early changes in glycaemia and to detect incidence of hypoglycaemia. At each visit, detailed clinical examination, assessment of patient diaries for hypoglycaemia episodes, and blood sugar (FBG and PPBG) were performed. Patients unwilling to follow up weekly were excluded. All patients were reminded telephonically to maintain adherence to study visits. Patients who did not return for follow up visit even after telephonic reminders within two days of scheduled visits were excluded from the study. Patients were asked to maintain a diary to record any events related to therapy. Patients were educated on symptoms of hypoglycaemia at baseline and were asked to record such symptoms with their relation to time and dosing of insulin in patient diaries. For each patient, adherence to continued lifestyle modification was ensured at each visit. Efficacy was assessed by glycaemic changes from baseline to 12 weeks in HbA1c, FBG and PPBG and achievement of goal HbA1c of
