Safety And Efficacy Of Empagliflozin In Pakistani Muslim Population With Type Ii Diabetes Mellitus (SAFE-PAK)

To compare the safety and efficacy of empagliflozin versus other treatments in Pakistani Muslim population with type II diabetes mellitus.

Study Overview

• Status: Completed
• Conditions: Type II Diabetes Mellitus
• Intervention / Treatment: Drug: Empagliflozin; Drug: Usual care group

Detailed Description

Diabetes is the one of the most common non-communicable diseases affecting 425 million adults worldwide. This figure is expected to rise to 629 million by the year 2045.1 90% of the diabetic population has type 2 diabetes. 2 As of 2018, more than 500 million individuals are residing with type 2 diabetes mellitus globally. 3 In Pakistan, the situation is similarly alarming. According to a recent survey, 16.98% of the Pakistani population has diabetes.4 The primary target of therapy in diabetes mellitus is optimum blood glucose control. In case of type 2 diabetes, this is achieved by a combination of oral hypoglycemic agents and injectable drugs with insulin as a last resort.

A number of oral agents targeting various sites of action are available. Sodium-glucose cotransporter-2 (SGLT2) inhibitors are newer class of drugs that have been introduced. They have a unique mechanism of action. By acting at the sodium glucose co-transporter, they block the reabsorption of glucose leading to an increase in urinary glucose excretion and lowering of plasma glucose.5 This action is completely independent of the beta cell function. There are several theoretical advantages to this approach. In addition to lowering blood glucose, the urinary glucose excretion results in loss of calories and weight reduction and the associated osmotic diuretic effect can aid in lowering blood pressures.6,7 Numerous studies have demonstrated a favorable risk benefit ratio of empagliflozin as monotherapy8 as well as add-on therapy to other hypoglycemic agents.9,10,11,12 They also have additional cardiovascular benefits with several studies documenting a reduction in mortality.13,14 Moreover, the sodium glucose co-transporters also demonstrated a reduction in the onset and worsening of nephropathy and preservation of renal function.15 This effect is not restricted to empagliflozin alone, as other drugs in the class have also demonstrated this benefit.16 Empagliflozin with its novel mechanism of action has its own set of side effects. Increased urinary glucose losses lead to a higher proportion of urinary tract infections and genital tract infections. This has been evidenced in various studies.17 The osmotic diuresis that benefits in lowering blood pressures at one end, also predisposes the patients to volume depletion.Empagliflozin, one of the three drugs from this class, approved by the FDA for treatment of type 2 diabetes. According to the recent ADA and the EASD guidelines, they have become an essential component of the algorithm recommended for managing type 2 diabetes.18 The recently published consensus statement by the South Asian Federation of Endocrine Societies has incorporated sodium glucose co-transporter 2 inhibitors in the treatment of patients with type 2 diabetes as monotherapy in patients who are intolerant to or have any contraindication to metformin therapy. Additionally, drugs belonging to this class are also recommended as combination therapy with other oral hypoglycemic agents as well as insulin.19 Empagliflozin, however, has not been studied in the Pakistani population as yet. The main aim of this study is to establish the efficacy and safety of empagliflozin in optimum control of blood sugar in type 2 diabetes. This is the first study of its kind being performed in the Pakistani population.

• Study Type: Interventional
• Enrollment (Actual): 244
• Phase: Phase 4

Contacts and Locations

Study Locations

• Pakistan
  • Balochistan
    • Quetta, Balochistan, Pakistan
      • Balochistan Medical Center
  • Khyber Pakhtunkhwa
    • Peshawar, Khyber Pakhtunkhwa, Pakistan
      • Lady Reading Hospital
    • Peshawar, Khyber Pakhtunkhwa, Pakistan
      • Post Graduate Medical Institute
  • Punjab
    • Islamabad, Punjab, Pakistan
      • Hanif Medical Center
    • Islamabad, Punjab, Pakistan
      • Shifa International Hospital
    • Lahore, Punjab, Pakistan
      • Jinnah Hospital
    • Lahore, Punjab, Pakistan
      • Diabetes Institute of Pakistan
    • Lahore, Punjab, Pakistan
      • National Defence Center
    • Multān, Punjab, Pakistan
      • Al-Khaliq Hospital
  • Sindh
    • Karachi, Sindh, Pakistan
      • Fatimiyah Hospital
    • Karachi, Sindh, Pakistan
      • National Institute of Cardiovascular Disease

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pakistani muslim male / female, type 2 diabetic patient having age from 18 years to 75 years
• Patient who give informed consent voluntarily
• BMI ≤45 kg/m2
• Glycosylated hemoglobin of 7 - ≤10%

Exclusion Criteria:

• Patients who are on empagliflozin treatment
• Indication of liver disease, defined by serum levels of either alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase above 3 times upper limit to normal
• Estimated glomerular filtration rate (eGFR) <45 mL /min /1.73m2
• History of recurrent urinary tract infection (UTI) and/or past 3 months' history of UTI and its treatment
• Patients with positive urine culture for UTI at the time of screening
• Patients who have been admitted to the hospital in the past 3 months for diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state
• Patients with past 3 months' history of fungal infection and its treatment
• History of blood dyscrasias or any disorders causing haemolysis or unstable red blood cell
• History of benign prostate hyperplasia
• Any acute coronary syndrome, stroke and/or transient ischemic attack (TIA) in the previous 3 months
• Any contraindication for patients to Biguanides, Sulfonylureas, DPP-IV inhibitors, SGLT-2 Inhibitors
• Treatment with anti-obesity drugs or any other treatment leading to unstable body weight
• Patients with past 6 weeks treatment history with systemic steroids or thyroid hormones or any other uncontrolled endocrine disorder except T2DM
• Pre-menopausal women who are nursing or pregnant or are of childbearing potential and not practicing an acceptable method of birth control
• Any other clinical condition that would jeopardize patients safety while participating in this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Empagliflozin	Drug: Empagliflozin; Group A: Empagliflozin 10/25 mg once daily with or without antidiabetic drugs; Other Names: Group A
Active Comparator: Usual Care Group	Drug: Usual care group; Group B: usual care group but without Empagliflozin with adjustment of therapy as the standard of care; Other Names: Group B

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants reported adverse events	Number of participants reported adverse events such as Hypoglycemic events, Hypotension, Dehydration, Urinary tract infection, Diabetic Ketoacidosis, Fungal infection or any other	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of participants achieved HbA1c level <7%	Frequency of participants achieved HbA1c level <7%	24 weeks
Frequency of participants achieved FBS level within normal range	Frequency of participants achieved FBS level within normal range	24 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants reduces weight during the therapy	Number of participants reduces weight during the therapy or mean reduction in weight overtime	24 weeks
Number of participants reduces BMI level as per WHO Asian classification during the therapy	Number of participants reduces BMI or mean reduction in BMI overtime	24 weeks
Number of participants reduces Waist circumference during the therapy	Number of participants reduces Waist circumference or mean reduction in BMI overtime	24 weeks
Number of participants changes systolic blood pressure and diastolic blood pressure during the therapy	Number of participants reduces systolic blood pressure and diastolic blood pressure or mean reduction in systolic blood pressure and diastolic blood pressure overtime	24 weeks
Number of participants changes LDL level and HDL Level during the therapy	Number of participants reduces LDL level and HDL Level or mean reduction in LDL level and HDL Level overtime	24 weeks
Mean score of diabetes mellitus quality of life	The instrument provides an overall scale score, as well as two subscale scores for 1) satisfaction with treatment, 2) adherence with Self Care Regimen. 15 Items are scored on a 5-point Likert scale and are of two general formats.One format asks about the frequency of negative impact of diabetes itself or of the diabetes treatment and provides response options from 1 (never) to 5 (all the time). The second format asks about satisfaction with treatment and quality of life and is scored from 1 (very satisfied) to 5 (very dissatisfied). Higher scores on DQOL items and subscales are, therefore, negatively valenced, indicating problem frequency or dissatisfaction.	24 weeks

Collaborators and Investigators

• Sponsor: Getz Pharma
• Investigators: Principal Investigator: A H Aamir, Post Graduate Medical Institute

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2019
• Primary Completion (Actual): September 15, 2020
• Study Completion (Actual): September 28, 2020

Study Registration Dates

• First Submitted: November 27, 2020
• First Submitted That Met QC Criteria: December 10, 2020
• First Posted (Actual): December 11, 2020

Study Record Updates

• Last Update Posted (Actual): December 11, 2020
• Last Update Submitted That Met QC Criteria: December 10, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Empagliflozin
• Other Study ID Numbers: GTZ-DM-001-19

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No