|Year : 2022 | Volume
| Issue : 3 | Page : 242-248
Real-world evidence of generic dapagliflozin: Relevance and results from Indian multicenter retrospective study
Bipin K Sethi1, Sanjay Kalra2, Supratik Bhattacharya3, Anand Kumar4, Madhukar Rai5, Manoj Kumar Srivastava6, Srinath A7, Ajay Budhwar8, Savita Jain9, Harish Mohan Rastogi10, Pramod Gandhi11, G Vijay Kumar12, Joe Georje13, Mahesh V Abhyankar14, Ashish Prasad14, Prashant Sarda14
1 Department of Endocrinology, CARE Hospital, Hyderabad, Telangana, India
2 Department of Endocrinology, Bharti Hospital, Karnal, Haryana, India
3 Department of Endocrinology, AMRI Hospital, West Bengal, Kolkata, India
4 Department of Endocrinology and Metabolism, Indira Gandhi Institute of Medical Sciences (IGIMS), Patna, Bihar, India
5 Department of Medicine, Institute of Medical Sciences, Banaras Hindu University (BHU), Varanasi, Uttar Pradesh, India
6 Manasvi Diabetes Clinic, Lucknow, Uttar Pradesh, India
7 Department of Endocrinology, BGS Gleneagles Global Hospital, Bangalore, Karnataka, India
8 Department of Endocrinology, Budhwar Super Speciality Clinic, Amritsar, Punjab, India
9 Dr. Savita Jain’s Clinic, Ludhiana, Punjab, India
10 Dr. Harish Mohan Rastogi Clinic, Meerut, Uttar Pradesh, India
11 Department of Endocrinology, Kingsway Hospitals, Nagpur, Maharashtra, India
12 Department of Endocrinology, Apollo Hospital, Chennai, Tamil Nadu, India
13 Endodiab Clinic, Kozhikode, Kerala, India
14 Scientific Services, USV Pvt Ltd, Mumbai, Maharashtra, India
|Date of Submission||09-Dec-2021|
|Date of Decision||30-Mar-2022|
|Date of Acceptance||27-May-2022|
|Date of Web Publication||26-Sep-2022|
Mr. Prashant Sarda
Arvind Vithal Gandhi Chowk, BSD Marg, Station Road, Govandi East, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
Objective: The objective was to evaluate the clinical experience and treatment patterns of generic dapagliflozin usage in different patient profiles in Indian settings. Materials and Methods: A retrospective, multicentric, real-world study included patients with type 2 diabetes mellitus (T2DM) (aged >18 years), inadequately controlled by existing antidiabetic therapy and receiving generic dapagliflozin as an add-on to existing oral antidiabetic drug(s) with or without insulin or switch therapy. Baseline characteristics and treatment-related outcomes were retrieved from the medical records and analyzed. Results: A total of 1935 patients were included, of which 1279 (66.1%) were males. The mean age was 57.4 years, and around half of the patients (51.4%) were aged from 45 to 60 years. Hypertension (55.9%) and dyslipidemia (19.8%) were the common comorbidities. The majority (n = 1122; 60%) of patients received dapagliflozin in combination with one or two antihyperglycemic drugs. More than half of the patients received metformin (56.8%) or sulfonylurea (52.3%) in combination with dapagliflozin. A dose of 10 mg (93.4%) was the most commonly used dose of dapagliflozin. The mean levels of glycated hemoglobin, fasting plasma glucose, and postprandial plasma glucose were significantly reduced to 1.1% (1.0–1.1), 30.5 mg/dL (29.2–31.9), and 57.5 mg/dL (55.1–59.9), respectively, after the initiation of dapagliflozin. A total of 1935 patients experienced weight changes during the treatment, of which 90.5% of patients showed weight loss. Hypoglycemic events were reported in 12.5% of patients. Physician global evaluation of efficacy and tolerability showed a majority of patients on a good-to-excellent scale (97.3% and 97.1%). Conclusion: Generic dapagliflozin showed a significant improvement in glycemic parameters and reduced body weight with low hypoglycemic events. The administration of dapagliflozin provided a good-to-excellent efficacy and tolerability profile in patients with T2DM. To the best of our knowledge, this is the first study confirming the efficacy, safety, and usefulness of generic dapagliflozin in patients with T2DM.
Keywords: Glycemic control, obesity, SGLT2 inhibitor, weight reduction
|How to cite this article:|
Sethi BK, Kalra S, Bhattacharya S, Kumar A, Rai M, Srivastava MK, Srinath, Budhwar A, Jain S, Rastogi HM, Gandhi P, Vijay Kumar G, Georje J, Abhyankar MV, Prasad A, Sarda P. Real-world evidence of generic dapagliflozin: Relevance and results from Indian multicenter retrospective study. J Diabetol 2022;13:242-8
|How to cite this URL:|
Sethi BK, Kalra S, Bhattacharya S, Kumar A, Rai M, Srivastava MK, Srinath, Budhwar A, Jain S, Rastogi HM, Gandhi P, Vijay Kumar G, Georje J, Abhyankar MV, Prasad A, Sarda P. Real-world evidence of generic dapagliflozin: Relevance and results from Indian multicenter retrospective study. J Diabetol [serial online] 2022 [cited 2022 Nov 30];13:242-8. Available from: https://www.journalofdiabetology.org/text.asp?2022/13/3/242/357124
| Introduction|| |
Disease burden of diabetes is continuously growing worldwide. In 2019, International Diabetes Federation (IDF) estimated that 463 million adults (20–79 years) had diabetes globally, and in 2021, new 74 million cases were diagnosed with diabetes. India alone had more than 69 million individuals with diabetes in 2015 and is predicted to upsurge 101 million individuals with diabetes by 2030. Therefore, an early diagnosis and timely implementation of appropriate management strategies are vital for better prognostic outcomes.
The primary goal of the management of type 2 diabetes mellitus (T2DM) is to achieve glycemic control. At present, a wide range of oral antidiabetic (OADs) agents are available to manage T2DM depending on the individual patients’ clinical profile, socioeconomic status, and easy availability of the drugs in the nearby area, while the choice of a glucose-lowering agent should be based on a patient-centered approach including the evaluation of efficacy, hypoglycemia risk, impact on weight, cost, and a history of atherosclerotic cardiovascular disease (CVD) to reduce both micro- and macrovascular complications.
Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a relatively newer class of OADs that have the potential to play an important role by inhibiting glucose reabsorption at the early segments of the proximal convoluted tubule, thereby promoting a novel insulin-independent mechanism of action for the management of T2DM. Dapagliflozin, a selective orally active SGLT2 inhibitor, has been recently approved in India (2015) for use in patients with T2DM as monotherapy or in combination with other OADs. Several clinical studies have evaluated dapagliflozin and demonstrated a significant reduction in glycated hemoglobin (HbA1c), body weight, and blood pressure.,, In addition, dapagliflozin was associated with cardio- and reno-protective properties, which were effective among a broad patient population.
Most of the randomized controlled trials on the use and efficacy of dapagliflozin in patients with T2DM were done in Western countries.,, Such evidence-based studies among the Indian populations are scarce. Therefore, the purpose of the present multicentric observational study was to retrospectively investigate the clinical utility pattern of generic dapagliflozin in patients with T2DM under real-world settings in India.
| Materials and Methods|| |
Design and study population
This retrospective, multicenter study (n = 208) was conducted between May 2021 and September 2021. Patients of either sex aged ≥ 18 years, having inadequately controlled T2DM (HbA1c >7%) with existing antidiabetic therapy, and who have initiated treatment with generic dapagliflozin, either as an add-on to existing OAD(s) with or without insulin or as switch therapy from another OAD in the past 6 months, were included in this study. Patients with renal impairment or CVD and patients with at least one additional traditional cardiovascular risk factor including dyslipidemia or hypertension were also included. Renal impairment was defined as estimated glomeruli filtration rate (eGFR) < 60 mL/min/1.73 m2 for 3 months or more. The patients having any condition that according to the discretion of the investigator indicates that the patient is not suitable for inclusion in the study were excluded from the analysis. The data relating to the demographic characteristics, duration of disease, comorbidities, concomitant medications, and dosage pattern were collected from medical records authenticated by physicians during routine care.
This was an observational study where we collected anonymous data from medical records. Hence, ethics committee approval was not obtained for this study.
The outcome of this data analysis was evaluated by the demographics of patients receiving different combination strengths of generic dapagliflozin with other OADs, change in HbA1c, postprandial plasma glucose (PPG) and fasting plasma glucose (FPG) levels, blood pressure levels, lipid parameters (total cholesterol, triglycerides, high-density lipoprotein [HDL-C], and low-density lipoprotein [LDL-C]), renal function parameters (eGFR) at 6 months from baseline, comorbidities and diabetic complications, usage of concomitant drugs with dapagliflozin, and medication adherence and safety profile during the course of the treatment. Hypoglycemic event was defined as <70 mg/mL or clinically based on physician’s discretion.
Data were analyzed using Statistical Package for the Social Sciences (SPSS) software, version 23.0. Demographic characteristics were summarized with descriptive statistics, including mean and standard deviation (SD) for continuous variables and frequency and percentages for categorical variables. A paired sample t-test was used for comparing the pre- and posttreatment glycemic parameters, blood pressure levels, body mass index (BMI), lipid parameters, and eGFR levels. A P < 0.05 was considered statistically significant.
| Results|| |
A total of 1935 patients were included in the study, of which 66.1% were males. The mean (SD) age of the patients was 57.4 (10.5) years, and 51.4% of patients were aged between 45 and 60 years. The mean duration of diabetes was 7.3 years and the HbA1c level at the time of treatment initiation was between 7.5% and 9% in 53.8% of patients. Obesity (42.5%) was the most common risk factor followed by a sedentary lifestyle (27.8%) and emotional stress (23.7%). The majority of patients had a family history of diabetes (48.4%), followed by hypertension (22.1%) and CVD (6.5%). Neuropathy (34.3%) was the most commonly observed diabetic complication followed by retinopathy (11.1%) [Table 1].
The majority of patients (60%) received generic dapagliflozin in combination with one or two OADs. The initiation of dapagliflozin as an add-on therapy was done in almost 90.9% of patients. The most common reasons for prescribing dapagliflozin were to achieve a better glycemic control (92.1%), to achieve weight loss (53.5%), and to reduce the risk of cardiovascular (CV) events and related hospitalization (50.4%). The majority of patients received dapagliflozin 10 mg (93.4%). More than half of the patients received metformin (56.8%) or sulfonylurea (52.3%) in combination with dapagliflozin [Table 2]. After treatment with dapagliflozin, 69.4%, 70.4%, and 74.1% of patients achieved optimal levels of blood pressure, lipid parameters, and renal function, respectively.
The mean levels of HbA1c, FPG, and PPG were significantly decreased after treatment with dapagliflozin. The reductions in HbA1c, FPG, and PPG level were 1.1% (1.0–1.1), 30.5 mg/dL (29.2–31.9), and 57.5 mg/dL (55.1–59.9), respectively. A significant improvement was observed in BMI, blood pressure, lipid parameters, and eGFR level [Table 3].
A normal balanced diet and low-carbohydrate and high-protein diet were recommended in 48.8% and 41.2% of patients, respectively. A regular exercise program was recommended in more than half (52.4%) of the patients. Compliance with medication was observed in 34.5% of patients. Among eligible patients, the total number of discontinuations was 479 (24.7%). The main reasons for discontinuation were inadequate HbA1c control (21.7%), intolerance (33.0%), and poor compliance (45.3%) [Table 4].
A total of 1935 patients experienced weight changes during the treatment, of which 90.5% of patients showed weight loss and 9.5% patients showed weight gain. The majority of the patients (48.9%) had weight reduction up to 2 kg. Overall, hypoglycemic events were reported in 12.5% of patients. Only 0.03% of patients (n = 55) developed urinary tract infection during the study. Physician global evaluation of efficacy (97.3%) and tolerability (97.1%) showed a majority of patients on a good-to-excellent scale. Physicians strongly recommended the use of dapagliflozin for primary prevention of CV events (strongly agree [44.1%] and agree [47.9%]). In addition, physicians strongly agreed (50.4%) that the cost-effectiveness of dapagliflozin has contributed to a better access in patients with T2DM [Table 4].
| Discussion|| |
According to American Diabetes Association (ADA), European Association for the Study of Diabetes (EASD), and American Association of Clinical Endocrinology (AACE) guidelines, SGLT2 inhibitors can be used as monotherapy or as add-on second- or third-line drugs in combination with pre-existing antihyperglycemic medications for the treatment of T2DM. These classes of drugs have a novel insulin-independent mechanism of action, which provided an adequate renal function along with glycemic control.,,,,,
Dapagliflozin is currently considered as a suitable therapeutic option as a first-line or second-line therapy for the treatment of T2DM. The present study evaluated the clinical experience and treatment patterns of generic dapagliflozin usage in various patient profiles in Indian settings. This real-world study conducted in outpatient practices will be an important step toward validating the effectiveness of this treatment pattern.
The key findings of this study showed that the majority of patients receiving dapagliflozin as an add-on or switch therapy belonged to the age group of 45–60 years. Obesity, sedentary lifestyle, emotional stress, and family history of diabetes were the common risk factors associated with these patients. The majority of patients with T2DM are associated with comorbid conditions including hypertension and dyslipidemia, whereas neuropathy was the most common diabetic complication in such patients. These observations are in accordance with the previous studies reporting a high prevalence of complications and comorbidities in T2DM.,,
In the present study, the majority of patients (60%) received dapagliflozin in combination with one or two antidiabetic drugs. A similar finding was reported by Chen et al. where 38.2% and 36.2% of patients received dapagliflozin in the form of dual- and triple-drug combination therapy, respectively. In addition, the recommended dose of dapagliflozin was 10 mg among 93.4% of patients, and an initiation of dapagliflozin as an add-on to almost 90% of patients was in congruence with the previous studies.,,
In this retrospective analysis of Indian patients with T2DM, the administration of dapagliflozin was found to reduce levels of HbA1c, FPG, PPG, and body weight. Previously published comprehensive reviews or meta-analyses have established the effectiveness of dapagliflozin as monotherapy and as add-on/combination therapy with existing antidiabetic treatment in patients with T2DM.,,,, Similarly, a recently published meta-analysis has evaluated the impact of dapagliflozin as monotherapy in reducing the level of HbA1c, FPG, and body weight without increasing the risk of hypoglycemia in patients with T2DM. A FOREFRONT study from India reported a significantly reduced mean HbA1c level (9.11% versus 8.11% versus 7.62%) and body weight (78.15 versus 77.01 versus 76.16 kg) from baseline to months 3 and months 6 after treatment with dapagliflozin. It is indicated that initial weight reduction may be due to the osmotic diuretic effect of dapagliflozin. However, constant weight loss over a subsequent period of time resulted in caloric loss due to glycosuria. Significant reduction in both systolic blood pressure (SBP) and diastolic blood pressure (DBP) was observed with a mean change of 12.1 mmHg and 5.8 mmHg, respectively. Similarly, previous studies reported clinical benefits of dapagliflozin in reducing SBP and DBP along with glycemic control.,,, Although the exact mechanism of action of the blood pressure-lowering effect of dapagliflozin is still not known, it has been postulated that the osmotic diuretic effect of dapagliflozin is associated with an increasing level of hematocrit. Besides these, the local inhibition of the renin-angiotensin-aldosterone system that occurs following an increased delivery of sodium to the juxtaglomerular apparatus is an additional mechanism by which SGLT2 inhibitor potentially induced a reduction in blood pressure. Similarly, there was a significant improvement in eGFR level after treatment with dapagliflozin. In several CV outcome trials of SGLT2 inhibitors, the cardio- and reno-protective effects came into the limelight. A large-scale randomized controlled trial and real-world studies (CVD-REAL study) reported that the use of dapagliflozin can be beneficial in reducing hospital stay for heart failure and CV mortality in patients with T2DM with an existing or a risk of CVD.,, Also, dapagliflozin has recently been approved in India for the treatment of heart failure with reduced ejection fraction. A higher proportion of patients with T2DM observed with mild-to-moderate renal impairment. According to recent DAPA-CKD trial, dapagliflozin has been shown to improve renal outcomes in patients with T2DM.
Hypoglycemic events were observed in 12.5% of patients. However, there are no major episodes of hypoglycemia. The incidence of hypoglycemic events reported in the present study was comparable with previously published literature.,,, SGLT2 inhibitors are associated with a relatively lower risk of hypoglycemia because of their insulin-independent mechanism of action, which is complementary to other hypoglycemic agents and insulin.
In the present study, physicians strongly agreed (50.4%) that the cost-effectiveness of dapagliflozin has contributed to treatment compliance and adherence. Recently, a study done by Sharma et al. reported that the low-cost dapagliflozin is beneficial in terms of improving metabolic outcomes, and cardio- and reno-protective effect. Among all SGLT2 inhibitors, dapagliflozin is a cost-effective therapy for a long-term management of T2DM. Also, the overall cost of generic dapagliflozin was assessed by recently published switched study, indicating generic UDAPA could improve compliance benefit compared with twice-daily formulations available in the market.
Indian clinicians are very familiar with the use of dapagliflozin in the management of T2DM either as an add-on or switch therapy. Physician global evaluation of efficacy and tolerability showed a majority of patients on a good-to-excellent scale (97.3% and 97.1%).
This was a real-world study depicting the clinical experience and treatment patterns of dapagliflozin usage in various patient profiles including patients with comorbidities and diabetic complications. A high insight for efficacy and tolerability was observed with an administration of dapagliflozin either as an add-on or switch therapy.
Although this study included a large patient population, it is limited because of its retrospective nature. Besides this, T2DM cases included in this study were enrolled from Indian healthcare centers, which may limit the extrapolation of these findings to the general population. The results need to be interpreted cautiously as different investigators from different sites were involved in this study. Additionally, missing data of patients who failed to report have limited the analysis strength of the study parameters.
| Conclusion|| |
In the present real-world study of Indian patients with T2DM, treatment with dapagliflozin, either as an add-on to existing OAD(s) with or without insulin or as a switch therapy from another OAD significantly improved glycemic parameters and reduced body weight with additional benefits of blood pressure-lowering effects and improvement in renal function over 6 months. The administration of dapagliflozin provided good-to-excellent efficacy and tolerability profile in patients with T2DM. Therefore, generic dapagliflozin appears to be a good treatment option for the effective management of T2DM. To the best of our knowledge, this is the first study confirming the efficacy, safety, and usefulness of generic dapagliflozin in patients with T2DM.
We acknowledge Mr. A. Thamburaj and Mr. Gajanan Mohite from USV Pvt Ltd, Mumbai, for their assistance in carrying out the project.
Financial support and sponsorship
The study was funded by USV Private Limited, Mumbai, India.
Conflict of interest
Dr Mahesh Abhyankar, Dr Ashish Prasad, Mr Prashant Sarda are employees of USV Pvt. Ltd. All other authors have no conflict of interest to declare.
All the authors have contributed equally to the work and fulfil ICMJE authorship criteria. All the authors have reviewed the final draft and approved the same.
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[Table 1], [Table 2], [Table 3], [Table 4]