Safety And Efficacy Of Empagliflozin In Pakistani Muslim Population With Type Ii Diabetes Mellitus

Type II Diabetes Mellitus Clinical Trial

— SAFE-PAK  

Official title:

Safety And Efficacy Of Empagliflozin In Pakistani Muslim Population With Type Ii Diabetes Mellitus

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04665284
• Other study ID #: GTZ-DM-001-19
• Status: Completed
• Phase: Phase 4
• Start date: June 1, 2019
• Est. completion date: September 28, 2020

Study information

• Verified date: December 2020
• Source: Getz Pharma
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: September 28, 2020
• Est. primary completion date: September 15, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type II Diabetes Mellitus

Intervention

Drug:
• Empagliflozin
Group A: Empagliflozin 10/25 mg once daily with or without antidiabetic drugs
• Usual care group
Group B: usual care group but without Empagliflozin with adjustment of therapy as the standard of care

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Getz Pharma

Country where clinical trial is conducted

Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of participants reduces weight during the therapy	Number of participants reduces weight during the therapy or mean reduction in weight overtime	24 weeks
Other	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
Other	Number of participants reduces Waist circumference during the therapy	Number of participants reduces Waist circumference or mean reduction in BMI overtime	24 weeks
Other	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
Other	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
Other	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
Primary	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	Frequency of participants achieved HbA1c level <7%	Frequency of participants achieved HbA1c level <7%	24 weeks
Secondary	Frequency of participants achieved FBS level within normal range	Frequency of participants achieved FBS level within normal range	24 weeks