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.

Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: an observational study.

BACKGROUND: Management of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin. METHODS: It was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021-June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin. RESULTS: Patients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group. CONCLUSION: SGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

Dapagliflozin: The outcome of use as add-on therapy in real-life clinical setting -An Audit.

OBJECTIVE: Dapagliflozin is the first novel sodium glucose co transporter 2 inhibitor for the treatment of Type 2 diabetes. The aim of this audit was to evaluate its effectiveness and safety in a real-life clinical setting. METHODS: We analyze data from four UK district general hospitals on patients initiated on dapagliflozin. HbA1c, weight and daily insulin dosage was recorded at baseline and 6 months follow-up. RESULTS: At baseline, mean HbA1c was 82±19.21mmol/mol(9.7%) and mean weight was 102±18.1kg. The average reduction in HbA1c at 6 months was 13±7.23 mmol/mol (1%) whereas the average reduction in weight was 2 ±2.02 kg.. A mean reduction in daily insulin requirement by 12±8.3 units at 6 months compared to baseline was noted. There were certain complications in patients taking insulin and gliclazide including candidiasis, urinary tract infection and hypoglycaemia, and 4% patients discontinued dapagliflozin due to side effects. CONCLUSIONS: Our results confirm that dapagliflozin can be used safely and effectively in a real-life setting.

Essential diagnostics and devices in primary care diabetes.

Medication is essential for diabetes care, and this is reflected in the Essential Medicines lists prepared by the World Health Organization and various countries. The need for essential diagnostics, and essential devices, however, has not been addressed adequately. In this communication, we call for creating a list of the essential diagnostics and devices that are required in primary and secondary/ tertiary diabetes care. We hope that this will encourage policymakers and clinicians to work together, to ensure that these are made available, accessible, and affordable for all patients.

Weight and Body Mass Index for Predicting Thyroxine Dose in Primary Hypothyroidism.

Background The treatment of primary hypothyroidism with thyroxine is weight-based or body mass index (BMI)-based. However, significant variation in the dose and the consequent delay in achieving euthyroid state is observed along the spectrum of patient body weights. Objectives To determine the weight and BMI-based dosing of thyroxine in primary hypothyroidism to achieve euthyroidism. Material and methods It was a retrospective review of the patient records conducted in the department of endocrinology, Shifa International Hospital, Islamabad, from July 1, 2014, to June 30, 2019 (five-year period). Patients with clinical and biochemical hypothyroidism were enrolled and initiated on thyroxine replacement to achieve euthyroid status. A total of 504 patients were included in the study. Results The mean age was 44.5 ±13.6 standard deviation. Females were 83.5%. The mean dose of thyroxine to achieve euthyroid status was 107.7 ± 39.3 mean standard deviation mcg/day, i.e. 1.4 (0.5) mcg/kg/day. Euthyroid status was achieved in 264 (52.4%) of patients at three months. The mean TSH level after treatment was 2.09 (1.2) mU/L. The linear regression model showed that BMI and weight are independent predictors of the required thyroxine dose (R and Rsquare values are .274 and 0.075 for BMI and .319 and .102 for weight, respectively (P-value <.0001). There was no impact of age, gender, height, and duration of disease on achieving euthyroid at six months after treatment (P values: .85, .394, .827, and .105, respectively). Conclusion The optimum dose in primary hyperthyroidism can be determined with body weight and BMI-based calculations.

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.

Efficacy and Safety of Dulaglutide in Type 2 Diabetes Patients in Endocrinology Clinics of Islamabad, Pakistan.

Objective: Our objective was to ascertain the efficacy and safety of once weekly Dulaglutide among patients with Type 2 diabetes of Pakistani origin. Methods: This prospective cohort study was conducted at the Endocrinology Clinics of Shifa International Hospital, Islamabad and Umar Diabetes and Foot Care Centre, Islamabad, Pakistan during the period from July 2020 to December 2020. Dulaglutide at the dose of 1.5 mg once weekly was initiated in patients with BMI >28 and suboptimal glucose control in the background of Type 2 Diabetes who were also taking one or more of oral anti-diabetic and/or insulin therapy. Results: Mean age of patient cohort (n = 148) was 49.51 years (SD +/- 12.15) with 53.5% (n = 85) having type 2 diabetes for a duration of over 10 years. Mean weight was 93.2 kg at baseline with end of study mean weight being 90.7 kg. Mean HbA1c at baseline was 9.2%, which improved to 8.05% at the end of study. The main side-effects were nausea in 32%, vomiting in 8%, and diarrhea in 7% with 19% discontinuation rate due to cost and side-effects. Conclusion: Dulaglutide as a therapy demonstrated favorable HbA1c and weight reduction in obese type 2 diabetes patients of Pakistani origin.

Effectiveness, Safety, and Patient Satisfaction of Liraglutide in Type 2 Diabetic Patients.

Background and Objectives Liraglutide, an analog of human glucagon-like peptide 1 (GLP-1), has been approved for the treatment of type 2 diabetes mellitus in Pakistan since 2016. It is a GLP-1 receptor agonist that has shown promising results in terms of not only glycemic control but also weight loss. Our study aimed to provide evidence regarding the safety and effectiveness of liraglutide in Pakistan and to look at the adherence rate and treatment satisfaction of patients using liraglutide. Methods This is an observational retrospective study that recruited patients who were treated with liraglutide. Data were collected at the first visit and follow-up. Morisky Green Levine Adherence Scale and Treatment Satisfaction Questionnaire for Medication (TSQM-9) were used for the determination of adherence and satisfaction with the treatment. Results A total of 70 patients were recruited in the study, The mean difference in weight, body mass index, glycated hemoglobin (HbA1C), systolic blood pressure, and diastolic blood pressure from baseline to follow-up was -5.36 kg, -2.14 kg/m2, -1.76%, -12.38 mmHg, and 5.55 mmHg, respectively. Nausea was the main side effect reported. TSQM-9 scores were compared from baseline, and it was found that patients are satisfied with the treatment and its effectiveness. Conclusions Our study has demonstrated the effectiveness of liraglutide as a monotherapy or combination therapy in the Pakistani population. Liraglutide led to reduction in HbA1C and weight. This is associated with high treatment satisfaction rate and adherence rate. Thus, liraglutide remains an effective though expensive treatment option in a country like Pakistan.

Thyroid Storm, a Mimicker of Guillain-Barre Syndrome: A Case Report.

A 60-year-old woman with diabetes mellitus presented to the emergency department (ER) with complaints of lower limb weakness, preceded by diarrhea. She complained of sweating and palpitations. There was no fever, cough, trauma, seizures, or headache. There was global weakness in all four limbs with absent reflexes and hypotonia. Examination of cranial nerves, the sensory system, and other systems was normal. Guillain-Barre syndrome (GBS) was suspected, but due to the patient's co-morbidities, treatment was withheld for 24 hours and the patient was kept under observation. Medical consultation was sought and thyroid function tests were ordered which showed thyroid-stimulating hormone (TSH) 0.019 uIU/ml (normal: 0.35-4.94 uIU/ml), free triiodothyronine (T3) 11.94 pg/ml (normal: 2.0-4.4 pg/ml), and free thyroxine (T4) >5 ng/dl (normal: 0.70-1.48 ng/dl). Thyroid storm was suspected and she was treated with hydrocortisone, propylthiouracil, Lugol iodine, and beta-blocker and her symptoms improved in 10 days with resolution of the weakness, confirming the diagnosis. Besides highlighting this association, this report demonstrates the importance of conducting thyroid function tests in patients presenting with axonal neuropathy. In patients having weakness in all four limbs and presenting with multiple comorbidities, we need to exclude medical reasons before starting treatment for GBS, such as in our case where it was thyrotoxicosis.

The Outcomes of Dapagliflozin Use in Real-Life Clinical Settings in Endocrinology Clinics of Islamabad, Pakistan.

Introduction Dapagliflozin is a member of a novel class of drugs (sodium-glucose cotransporter-2 inhibitors) used to treat type 2 diabetes mellitus and licensed in Pakistan in 2017. This retrospective observational study evaluated the effects of dapagliflozin on glycated hemoglobin (HbA1c) concentrations in patients treated at endocrinology clinics in Islamabad, Pakistan. The secondary objectives included assessing the effects of dapagliflozin on weight reduction and blood pressure control and to determining its safety. Methodology Patients with type 2 diabetes who were treated with dapagliflozin were identified by screening the electronic medical records at tertiary care hospitals in Islamabad. Data were collected at the first visit and at follow-up. Categorical variables were recorded as frequencies and percentages and compared by McNemar's tests, and continuous variables were recorded as means and standard deviations and compared by paired sample t-tests. Results Mean HbA1C concentration was significantly lower at follow-up than at the first visit (7.57%±0.98% vs. 9.07%±2.07%, respectively; p<0.001). Bodyweight (85.09±15.92 kg vs. 87.07±16.11 kg, respectively; p<0.001) and diastolic blood pressure (80.34±7.12 mmHg vs. 82.34±9.61 mmHg, respectively; p<0.001) were also significantly lower at follow-up than at the first visit, whereas systolic pressure showed a marginally significant reduction (123.5±16.57 mmHg vs. 126.83±19.97 mmHg, p=0.048). Conclusion This first observational study of patients in Pakistan treated with dapagliflozin found that HbA1c concentration, weight, and blood pressure were reduced after initiation of dapagliflozin treatment.

Prevalence of undiagnosed type 2 diabetes in patients admitted with acute coronary syndrome: the utility of easily reproducible screening methods.

BACKGROUND: Despite the recognition of the importance of diagnosing dysglycaemia in patients with acute coronary syndrome (ACS) there remains a lack of consensus on the best screening modality. Our primary aims were to determine the prevalence of undiagnosed dysglycaemia and to compare the OGTT and HbA1c criteria for diagnosis of T2DM in patients admitted to hospital with ACS at baseline and at 3-months. We also aimed to investigate the role of a screening algorithm and a predictor score to define glucose tolerance in this population. METHODS: A prospective study in which patients admitted with ACS to two UK teaching hospitals were assessed at baseline and 3 months follow-up. RESULTS: The prevalence of diabetes at baseline was 20% and 16% based on OGTT and HbA1c criteria respectively. Forty three (43) % of the patients with T2DM based on OGTT would have been missed by the HbA1c criteria at baseline. Our screening algorithm identified 87% of patients with T2DM diagnosed with OGTT. Diabetes Predictor score had better sensitivity (>80%) and negative predictive value (>90%) compared to HbA1c criteria. Two thirds of participants with IGS and a third with T2DM changed their glycaemic status at 3 months. CONCLUSIONS: Only 48% of the patients admitted with ACS had normo-glycaemia based on OGTT. OGTT and HbA1c identified two different populations of patients with dysglycaemia with the HbA1c criteria missing almost half the patients with T2DM based on OGTT. Compared to HbA1c criteria our diabetes algorithm and diabetes predictor score had a better correlation with OGTT criteria.

Longstanding insulin dependent diabetics may not require insulin after the introduction of GLP-1 analogues.

Glucagon like peptide (GLP-1) analogues are a relatively novel medication developed primarily for the treatment of type 2 diabetes since 2005. Although GLP-1 analogues have been shown to be more effective in the first few years of diagnosis in type 2 diabetes, we report a case of a patient with longstanding insulin-dependent diabetes started on a GLP-1 analogue, liraglutide, who now has controlled blood sugars without the need of insulin.