Safety and efficacy of Empagliflozin in Pakistani Muslim patients with type 2 diabetes (SAFE-PAK); a randomized clinical trial.

BACKGROUND: Sodium-Glucose-Co-Transporter 2 (SGLT2) inhibitor (Empagliflozin) is an effective drug in controlling blood glucose through predominantly glycosuria. Glycosuria increases the risk of genitourinary infections in diabetes. This study was aimed to establish the safety and efficacy of Empagliflozin (Group-A) versus standard care (Group-B) in Pakistani Muslim individuals with type 2 diabetes. METHODS: A multicenter, randomized clinical trial was conducted in five cities across Pakistan from July 2019 to August 2020. Patients of both genders aged 18-75 years, body mass index (BMI) ≤ 45 kg/m2, glycosylated hemoglobin (HbA1c) 7-10% (53 mmol/mol to 86 mmol/mol) and treatment-naive to Empagliflozin were included. Treatment was given for 24 weeks, and allocation was done through randomization. RESULTS: Out of 745 screened patients, 333 met the eligibility criteria, and a total of 244 (73.3%) patients were enrolled. More hypoglycemic events were reported in the standard care group, whereas positive urine culture, fungal infection, dehydration, and hypotension occurrence were comparable between the two groups. The 6 months mean HbA1c reduction was significant in both groups; (Group-A: 0.91 ± 0.15; p < 0.001 vs. Group-B2: 0.79 ± 0.14; p < 0.001). Efficacy comparison at 6 months revealed a significant reduction in weight and systolic blood pressure (SBP) in Group A only (Group-A: 1.4 ± 0.4 kg; p < 0.002 vs. Group-B: 0.01 ± 0.5 kg; p < 1.00), (Group-A: 5.1 ± 1.7 mmHg; p < 0.012 vs. Group-B: 2.3 ± 1.7 mmHg; p < 0.526). CONCLUSIONS: Empagliflozin was a safe drug compared to standard care in Pakistani Muslim patients with diabetes. It was as effective as standard care in the clinical setting but achieved glycemic control by reducing weight and SBP in type 2 diabetes patients. TRIAL REGISTRATION: This study was registered in the NIH US National Library of Medicine clinical trials registry at Clinicaltrials.gov with the registration number: NCT04665284 on 11/12/2020.

Asymptomatic urinary tract infections and associated risk factors in Pakistani Muslim type 2 diabetic patients.

BACKGROUND: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic. METHODS: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients. RESULTS: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin. CONCLUSION: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.

Expert Opinion: Use of sodium glucose co-transporter type-2 inhibitors in South Asian population -The Pakistan perspective.

Sodium-glucose co-transporter type 2 inhibitors (SGLT 2- i)are increasingly being used in the management of type 2 diabetes mellitus (T2DM). With the novel insulinindependent glycosuric action, these agents help to attain glycaemic goals by lowering HbA1c and fasting blood glucose. In addition, these agents improve metabolic control in diabetes and ameliorate comorbidities like obesity and hyper tension. Beneficial effec ts on cardiovascular outcomes have been a key attraction for physicians. These agents are used alone or in combination with oral antidiabetic agents and insulin to attain glycaemic and metabolic targets. A major disadvantagewith these agents is the increased risk for genital andurinary infections. When used in appropriate settings, there is no additional increased risk of hypoglycaemia or volume depletion with these agents. Available evidence suggests good efficacy and safety of these agents in diabetes management. The easy and convenient oncedaily dosing should be customized according to patient needs and glycaemic profiles.

Cardiovascular disease risk factors in Pakistani population with newly diagnosed Type 2 diabetes mellitus: A cross-sectional study of selected family practitioner clinics in four provinces of Pakistan (CardiP Study).

OBJECTIVE: To explore cardiovascular risk factors in people with newly-diagnosed type 2 diabetes mellitus. METHODS: The cross-sectional, prospective, multicentre, study was conducted from June 2014 till July 2015 at family practice clinics in 27 cities across Pakistan, and comprised individuals aged 30-50 years diagnosed with type 2 diabetes mellitus within the preceding six months. Laboratory investigations were conducted at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, and Aga Khan University Hospital, Karachi. The 10-year absolute risk of fatal or non-fatal coronary heart disease and stroke was calculated using the United Kingdom Prospective Diabetes Study Risk Engine version 2.0. Data were analysed using SPSS 19. RESULTS: Out of 888 subjects, 362(40.8%) were women and 526(59.2%) were men. The overall mean presenting age was 42.4}5.8 years. After stratification by age, those ≥40 years were significantly associated with higher glycated haemoglobin (p=0.02) and those ≤39 years were associated with higher levels of very low density lipoprotein (p=0.001) and triglyceride (p=0.006). The mean risk estimate for CHD was 9.7% (95% Confidence Interval (CI) 9.0- 10.1)), for fatal CHD 4.4% (95% CI 4.0-4.6), for stroke 1.5% (95% CI 1.2-1.7), and for fatal stroke 0.25% (95% CI 0.24- 0.26). CONCLUSIONS: There is a need for screening cardiovascular risk factors even in younger age groups of newlydiagnosed diabetes.

Type 2 diabetes prevalence in Pakistan: what is driving this? Clues from subgroup analysis of normal weight individuals in diabetes prevalence survey of Pakistan.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a global health tissue. We determined factors relating to the likelihood of developing T2DM in normal BMI individuals. METHODOLOGY: This was a cross-sectional community-based representative survey, of people aged ≥20 years in Pakistan, using HBA1c as the screening tool. The prevalence of T2DM/prediabetes in people having normal BMI together with associated risk factors was estimated. RESULTS: Of 6824 normal BMI individuals, there was still a high prevalence of T2DM 14.92% and in underweight at 10.14% (overall prevalence 16.96%). Corresponding rates for prediabetes for the normal BMI category: 9.79% and underweight 8.99%. Multivariate logistic regression modeling for normal BMI individuals, showed a significantly increased risk of T2DM with increasing age (odds ratio [OR] 2.1, 3.3, 4.5 and 4.8, P < 0.001 for 31-40, 41-50, 51-60 and 61 years and above respectively, compared to age decade 20-30 years). Similarly, there was a significantly high risk of T2DM with lower education level [OR for no vs graduate 2.4, 95% confidence interval (CI) 1.5-3.8]. There was a significantly increased risk of T2DM in individuals having a positive family history [OR 4.3 (95% CI 7.0-11.5)]. Overall the influence of overweight/obese on T2DM occurrence (20% increased risk) was much less than in other regions of the world. CONCLUSION: There are higher than expected rates of T2DM/prediabetes in Pakistani ethnicity normal BMI individuals. Targeted screening of older individuals with historical lack of educational opportunity, with a family history of T2DM even if of normal BMI may result in a significant benefit in the Pakistan population.

Diabetes Prevalence Survey of Pakistan (DPS-PAK): prevalence of type 2 diabetes mellitus and prediabetes using HbA1c: a population-based survey from Pakistan.

OBJECTIVES: We conducted a Pakistan-wide community-based survey on the prevalence of type 2 diabetes using glycated haemoglobin (HbA1c) as the screening test. The aim was to estimate diabetes prevalence across different demographic groups as well as all regions of Pakistan. DESIGN, SETTINGS AND PARTICIPANTS: Multistaged stratified cluster sampling was used for the representative selection of people aged ≥20 years, residing in 378 sampled clusters of 16 randomly selected districts, in this cross-sectional study. Eligible participants had blood drawn for HbA1c analyses at field clinics near to their homes. The oral glucose tolerance test (OGTT) was conducted on a subsample of the participants. Overall and stratified prevalence of type 2 diabetes and its association with risk factors were estimated using logistic regression models. MAIN OUTCOME MEASURES: Prevalence of prediabetes and type 2 diabetes. RESULTS: Of 18 856 eligible participants the prevalence of prediabetes was 10.91% (95% CI 10.46 to 11.36, n=2057) and type 2 diabetes was 16.98% (95% CI 16.44 to 17.51, n=3201). Overall, the mean HbA1c level was 5.62% (SD 1.96), and among newly diagnosed was 8.56% (SD 2.08). The prevalence was highest in age 51-60 years (26.03%, p<0.001), no formal education (17.66%, p<0.001), class III obese (35.09%, p<0.001), family history (31.29%, p<0.001) and female (17.80%, p=0.009). On multivariate analysis, there was a significant association between type 2 diabetes and older age, increase in body mass index and central obesity, positive family history, and having hypertension and an inverse relation with education as a categorical variable. On a subsample (n=1027), summary statistics for diagnosis of diabetes on HbA1c showed a sensitivity of 84.7%, specificity of 87.2% and area under the receiver operating characteristic curve 0.86, compared with OGTT. CONCLUSIONS: The prevalence of type 2 diabetes and prediabetes is much higher than previously thought in Pakistan. Comprehensive strategies need to be developed to incorporate screening, prevention and treatment of type 2 diabetes at a community level.