|Year : 2020 | Volume
| Issue : 3 | Page : 210-213
Baseline characteristics of patients with type 2 diabetes mellitus initiating dapagliflozin in Saudi Arabia: Results from postauthorization safety study
Abdullah M Alguwaihes
Department of Internal Medicine, College of Medicine, King Saud University, Riyadh, Saudi Arabia
|Date of Submission||06-Nov-2019|
|Date of Decision||25-Dec-2019|
|Date of Acceptance||26-Jan-2020|
|Date of Web Publication||02-Jul-2020|
Abdullah M Alguwaihes
Department of Internal Medicine, College of Medicine, King Saud University Riyadh
Source of Support: None, Conflict of Interest: None
Context: There are limited reports in the literature regarding treatment with dapagliflozin in actual clinical settings in Saudi Arabia. Aims: The primary objective is to examine the safety profile of dapagliflozin in uncontrolled patients with type 2 diabetes mellitus (T2DM) in Saudi Arabia. In this brief report, we describe the baseline characteristics of patients initiating dapagliflozin in Saudi Arabia. Settings and Design: Prospective regulatory postmarketing study that was conducted in governmental and private hospitals in Riyadh and Jeddah, Saudi Arabia. Subjects and Methods: Five hundred T2DM patients initiating dapagliflozin at the decision of the treating physician as indicated by the Saudi Food and drug authority. Statistical Analysis Used: Data were statistically described in terms of frequencies and percentages for categorical variables. Mean, standard deviations (SD), minimum and maximum were used to describe the numerical variables. Results: At baseline, a total of 503 patients (female 38.8%, male 61.2%, and mean [SD] age 50.9 [10.1] years) were eligible for the analysis. Their mean body mass index was 32.8 (6.5) kg/m2. The mean duration of diabetes was 8.9 (8.3) years. Comorbidities were reported in 62% of our eligible population: 50.5% with hyperlipidemia and 39.6% with hypertension. Mean HbA1c at baseline was 8.6 (1.6) %, mean fasting blood glucose was 183.2 (70.1) mg/dL, and mean postprandial blood glucose was 237.8 (94.1) mg/dL. Conclusion: Recruited patients were matching our eligibility criteria and were representing average diabetic patients in the local community.
Keywords: Dapagliflozin, HbA1c, PASS, patients' characteristics, Saudi Arabia
|How to cite this article:|
Alguwaihes AM. Baseline characteristics of patients with type 2 diabetes mellitus initiating dapagliflozin in Saudi Arabia: Results from postauthorization safety study. J Nat Sci Med 2020;3:210-3
|How to cite this URL:|
Alguwaihes AM. Baseline characteristics of patients with type 2 diabetes mellitus initiating dapagliflozin in Saudi Arabia: Results from postauthorization safety study. J Nat Sci Med [serial online] 2020 [cited 2021 Jun 13];3:210-3. Available from: https://www.jnsmonline.org/text.asp?2020/3/3/210/282285
| Introduction|| |
Diabetes mellitus (DM) is a metabolic disorder characterized by chronic hyperglycemia. It results from defects in insulin secretion, insulin action, or both., The chronic hyperglycemia of diabetes causes long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels.,
In 2014, the global prevalence of diabetes among adults was 8.5%. In 2016, diabetes was the direct cause of 1.6 million deaths. According to the International Diabetes Federation in the eighth edition of the diabetes atlas, approximately 38.7 million people, or 9.6% of adults aged 20–79 years, were living with diabetes in the MENA region in 2017. About 49.1% of these were undiagnosed. The age-adjusted comparative prevalence of diabetes in Saudi Arabia is 17.7%, the highest among MENA countries.
DM falls into two main categories; Type 1 diabetes is caused by an absolute deficiency of insulin secretion due to autoimmune destruction of pancreatic β-cells, and Type 2 diabetes mellitus which is the more prevalent type, is caused by a combination of resistance to insulin action and an inadequate compensatory insulin secretory response., Type 2 diabetes mellitus (T2DM) is also characterized by a progressive deterioration of glucose tolerance over several years.
Impairment of insulin secretion and defects in insulin action frequently coexist in the same patient, and it is often unclear which abnormality, if either alone, is the primary cause of the hyperglycemia.
There are different treatment lines for DM targeting insulin sensitivity, glucose level, and excretion, one novel type of these treatments is inhibitors of sodium-glucose cotransporter type 2 (SGLT2) used for the management of T2DM. The available SGLT2 inhibitors share similar pharmacokinetic characteristics, with rapid oral absorption, a long elimination half-life allowing once-daily administration, an extensive hepatic metabolism mainly through glucuronidation to inactive metabolites, the absence of clinically relevant drug-drug interactions and a low renal elimination as parent drug.
Almost 90% of the glucose filtered by the kidneys is reabsorbed by SGLT2 cotransporters. The pharmacological inhibition of SGLT2 cotransporters reduces hyperglycemia by decreasing renal glucose threshold and thereby increasing urinary glucose excretion. The amount of glucose excreted in the urine depends on both the level of hyperglycemia and the glomerular filtration rate. The most frequently reported adverse events (AEs) are female genital mycotic infections, while urinary tract infections (UTIs) are less commonly observed and generally benign. Although AE profile is not established locally, it is predicted that UTIs and GTIs are less common due to the local practice of hygiene.
Dapagliflozin is a member of the SGLT2 inhibitors class; it was proved to improve hyperglycemia in uncontrolled patients with newly diagnosed T2DM. It also facilitates weight loss and reduces blood pressure by inducing controlled glucosuria with urinary loss of 200–300 kcal/day. Dapagliflozin treatment demonstrated no persistent, clinically significant osmolarity, volume, or renal status changes, also it results in a similar reduction in hemoglobin A1c compared to other oral antihyperglycemic drugs, which is preserved over 4 years of treatment.
Dapagliflozin is considered an addition to existing treatment options for T2DM due to the advantage of low risk of hypoglycemia due to insulin-independent mechanisms of action, body weight loss, and blood pressure reduction.,, Finally, based on recent economic evaluations, dapagliflozin seems to be a cost-effective option for T2DM in some settings.
The primary objective of this multicenter study is to examine the safety profile of dapagliflozin in uncontrolled patients with T2DM in Saudi Arabia; this includes all AEs, especially diabetic ketoacidosis (DKA) and UTIs, reported during the observation period. Secondarily, to record changes in HbA1c% from baseline in the study population during the same period.
In this report, we aim to describe the baseline characteristics of T2DM patients initiating dapagliflozin in Saudi Arabia during the recruitment period. The final results of our study will be published on the study completion.
| Subjects and Methods|| |
The sample population included adult patients with T2DM, aged between 18 and 75 years, who initiated treatment with 10 mg or 5 mg of dapagliflozin for the first time in accordance with the approved Saudi Arabia product label. All patients were required to read, understand, and sign informed consent forms before any study-related activities.
Patients with contraindications for the use of dapagliflozin (as described in the Saudi Arabia product label), or with repeated occurrences of DKA defined as any reported cases of DKA in the patient history “As per physicians reporting,” or patient utilizing other SGLT2 inhibitors rather than dapagliflozin were excluded.
Study design and data collection
This is a local, prospective, noninterventional, regulatory postmarketing study conducted based on a request from the Local Regulatory Authority (Saudi Food and Drug Administration[SFDA]) to observe the safety profile of dapagliflozin including the incidence of DKA in the setting of routine practice for T2DM in adult patients in Saudi.
Each patient will be followed for 52 weeks. In addition, an unscheduled, over the phone assessment will be conducted in Ramadan. The total study duration is planned to be 2 years; 1 year for recruitment and 1 year for treatment and observation. Patients with available baseline data in June 2018 were included in this report.
Sample size calculation
It is estimated that the number of T2DM patients exposed to dapagliflozin during the first postauthorization year in Saudi Arabia would be 15,000. About 10% of the total number of patients subjected to the medication during the 1st year (i.e., 1500 patients). However, because dapagliflozin has not yet been included in the formularies of many governmental hospitals in Saudi Arabia, the SFDA approved the reduction of the sample size to 500 patients.
Data were statistically described in terms of frequencies and percentages for categorical variables. Mean, standard deviations (SD), minimum and maximum were used to describe the numerical variables. All statistical calculations were done using computer program IBM SPSS (Statistical Package for the Social Science; IBM Corp, Armonk, NY, USA) release 21 for Microsoft Windows.
| Results|| |
During the period between May 2017 and June 2018, a total of 526 patients were enrolled in eight active sites across Saudi Arabia. Of these, 23 patients were excluded from the study. The reasons for exclusion are detailed in [Figure 1].
Of the 503 eligible patients, data revealed that 309 patients (61.2%) were male, and the mean (SD) age was 50.9 (10.1) years. Four hundred and fifty-five patients (90.5%) were Arabs, 36 (7.2%) were Asians, eight were (1.6%) people of African descent, and four (0.8%) were of other races. The mean weight was 90.3 (19.8) kg, height – 166.1 (10.9) cm, and body mass index (BMI) – 32.8 (6.5) kg/m 2.
The mean HbA1c value was 8.6 (1.6) %, fasting blood glucose (FBG) – 183.2 (70.1) mg/dL, and post prandial blood glucose (PPBG) – 237.8 (94.1) mg/dL. The mean low-density lipoprotein was 102.5 (33.3) mg/dL, high-density lipoprotein – 43.2 (12.4) mg/dL, triglycerides – 181.7 (128.6) mg/dL, and cholesterol – 172.3 (42.4) mg/dL. Data also showed that the mean alanine transaminase value was 29.5 (16.8) IU/L, aspartate transaminase – 18.8 (9.8) IU/L, albumin – 37.6 (3.8) g/L, and serum creatinine – 69.9 (17.5) umol/L. The mean duration of T2DM diagnosis was 8.9 (8.3) years. More details are provided in [Table 1].
At baseline, we found that 62% (n = 312) of our eligible population had comorbidities. Approximately half of the patients (50.5%) had hyperlipidemia, and around one-third (39.6%) had hypertension. More details about comorbidities are provided in [Table 2].
At study entry, 62.3% of patients were on biguanides, 42.8% were on dipeptidyl peptidase-4 inhibitors, 35% were on sulfonylureas, 12.2% were on glucagon-like peptide-1 receptor agonist, 3.7% were on thiazolidinediones, and 1% and 0.4% were on alpha-glucosidase inhibitors and meglitinides, respectively. Patients continued to receive these medications in combination with dapagliflozin during the study. More details are provided in [Table 3].
| Discussion|| |
This report aims to describe the baseline characteristics of our population.
Comparable results were reported in a noncomparative, prospective, noninterventional, regulatory postmarketing surveillance study that was conducted in Korea; it was found that dapagliflozin responders (T2DM patients who received 10 mg/day dapagliflozin) were 48.9% males, and the mean age was 52.8 (1.1) years, and the mean BMI was 28.1 (4.4) kg/m 2. The median duration of diabetes was 2.2 years. The baseline mean HbA1c, FBG, and PPBG were 8.1 (1.3) %, 166.2 (48.8) mg/dL, and 233.1 (80.4) mg/dL, respectively. When compared to that study, a higher percentage of male patients (61.2%), higher BMI (32.8 [6.5] kg/m 2), and longer duration of diabetes (8.9 [8.3] years) were observed in our population.
In a pooled analysis of dapagliflozin' safety data from phase IIb/III clinical trials in patients with T2DM, it was found that 54.6% of the 21-study pool were males and the mean age was 56.9 (10.4) years. The mean duration of diabetes was 7.0 (7.5) years. The baseline mean HbA1c and FBG were 8.21 (1.03) % and 167.2 (48.8) mg/dL, respectively; while in the 13-study pool, 57.5% were male and the mean age was 58.4 (10.02) years. The baseline mean HbA1c and FBG were 8.18 (0.94) % and 164.8 (46.6) mg/dL, respectively.
| Conclusion|| |
Recruited patients were matching our eligibility criteria and were representing average diabetic patients in the local community. The final results of our study will be published on the study completion.
We would like to thank all participating co-investigators for their valuable contribution in this study.
Co-investigators in alphabetical order: Abdel Hamid Hassan (International Medical Center), Abdullah Kamal Omer (Dallah Hospital), Ahmed Awad (Dallah Hospital), Ahmed Elsadek (Suleman Al Habeeb-Al Rayan), Amin Kemawy (King Abdulaziz University Medical Center), Amjad Kafelghazal (Suleman Al Habeeb-Olaya), Heba Bzeih (International Medical center), Hiba Adam (King Khalid University Hospital), Hilali Hassan Hilali (Dallah Hospital), Maha Hemadn (Suleman Al Habeeb-Al Rayan), Mohammed Batais (King Khalid University Hospital), Mowaia Mustafa (Suleman Al Habeeb-Olaya), Naweed Alzamman (Tayba University Hospital), Nidal Abu Diab (Specialized Medical Center Hospital), Ola Jarrad (Specialized Medical Center Hospital), Osman Wardy (Suleman Al Habeeb-Al Rayan), Rafif Farahat (Suleman Al Habeeb-Al Takhsusi), Saeed Taha (Suleman Al Habeeb-Al Takhsusi), Saher Safarini (Dallah Hospital), Said Khader (Suleman Al Habeeb-Olaya Medical Complex), Salah Kouta (Suleman Al Habeeb-Al Sewedy), Samia El Shiekh (Dallah Hospital), Samir Arif (King Khalid University Hospital), Syed Salman (Specialized Medical Center Hospital), Tarek Motawaea (Specialized Medical Center Hospital), Turky Almugbil (King Khalid University Hospital), and Waleed Maghawry Saleh (King Abdulaziz University Medical Center).
Data management and statistical analyses were provided by DATACLin Contract Research Organization and was funded by AstraZeneca KSA. Editorial support of this article was provided by Omnia Aboutaleb on behalf of DATACLin Contract Research Organization and was funded by AstraZeneca KSA.
Financial support and sponsorship
This study was funded by AstraZeneca KSA.
Conflicts of interest
The author received honorarium for lectures from multiple medical companies and participated in advisory board meetings for multiple medical companies.
| References|| |
Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 1998;15:539-53.
Weyer C, Bogardus C, Mott DM, Pratley RE. The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus. J Clin Invest 1999;104:787-94.
Shaikh S, Rizvi SM, Shakil S, Riyaz S, Biswas D, Jahan R. Forxiga (dapagliflozin): Plausible role in the treatment of diabetes-associated neurological disorders. Biotechnol Appl Biochem 2016;63:145-50.
Scheen AJ. Pharmacodynamics, efficacy and safety of sodium-glucose co-transporter type 2 (SGLT2) inhibitors for the treatment of type 2 diabetes mellitus. Drugs 2015;75:33-59.
List JF, Woo V, Morales E, Tang W, Fiedorek FT. Sodium-glucose cotransport inhibition with dapagliflozin in type 2 diabetes. Diabetes Care 2009;32:650-7.
Liakos A, Karagiannis T, Bekiari E, Boura P, Tsapas A. Update on long-term efficacy and safety of dapagliflozin in patients with type 2 diabetes mellitus. Ther Adv Endocrinol Metab 2015;6:61-7.
Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: A randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2010;33:2217-24.
Han E, Kim A, Lee SJ, Kim JY, Kim JH, Lee WJ, et al
. Characteristics of Dapagliflozin Responders: A Longitudinal, Prospective, Nationwide Dapagliflozin Surveillance Study in Korea. Diabetes Ther 2018;9:1689-701.
Jabbour S, Seufert J, Scheen A, Bailey CJ, Karup C, Langkilde AM. Dapagliflozin in patients with type 2 diabetes mellitus: A pooled analysis of safety data from phase IIb/III clinical trials. Diabetes Obes Metab 2018;20:620-8.
[Table 1], [Table 2], [Table 3]