Clinical trial NCT04665284: Safety And Efficacy Of Empagliflozin In Pakistani Muslim Population With Type Ii Diabetes Mellitus
Official title: Safety And Efficacy Of Empagliflozin In Pakistani Muslim Population With Type Ii Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type II Diabetes Mellitus
Lead sponsor: Getz Pharma
Sponsor class: INDUSTRY
First posted: 2020-12-11
Enrollment: 244
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of participants reported adverse events
timeFrame: 24 weeks
Secondary outcomes:
measure: Frequency of participants achieved HbA1c level <7%
timeFrame: 24 weeks
measure: Frequency of participants achieved FBS level within normal range
timeFrame: 24 weeks
Other outcomes:
measure: Number of participants reduces weight during the therapy
timeFrame: 24 weeks
measure: Number of participants reduces BMI level as per WHO Asian classification during the therapy
timeFrame: 24 weeks
measure: Number of participants reduces Waist circumference during the therapy
timeFrame: 24 weeks
measure: Number of participants changes systolic blood pressure and diastolic blood pressure during the therapy
timeFrame: 24 weeks
measure: Number of participants changes LDL level and HDL Level during the therapy
timeFrame: 24 weeks
measure: Mean score of diabetes mellitus quality of life
timeFrame: 24 weeks
Locations:
city: Quetta
country: Pakistan
facility: Balochistan Medical Center
state: Balochistan
city: Peshawar
country: Pakistan
facility: Lady Reading Hospital
state: Khyber Pakhtunkhwa
city: Peshawar
country: Pakistan
facility: Post Graduate Medical Institute
state: Khyber Pakhtunkhwa
city: Islamabad
country: Pakistan
facility: Hanif Medical Center
state: Punjab
city: Islamabad
country: Pakistan
facility: Shifa International Hospital
state: Punjab
city: Lahore
country: Pakistan
facility: Diabetes Institute of Pakistan
state: Punjab
city: Lahore
country: Pakistan
facility: Jinnah Hospital
state: Punjab
city: Lahore
country: Pakistan
facility: National Defence Center
state: Punjab
city: Multān
country: Pakistan
facility: Al-Khaliq Hospital
state: Punjab
city: Karachi
country: Pakistan
facility: Fatimiyah Hospital
state: Sindh
city: Karachi
country: Pakistan
facility: National Institute of Cardiovascular Disease
state: Sindh
Study officials:
affiliation: Post Graduate Medical Institute
name: A H Aamir
role: PRINCIPAL_INVESTIGATOR
References: