http://hdl.handle.net/123456789/247 2026-04-04T10:42:16Z http://hdl.handle.net/123456789/20708 CLINICAL EFFICACY AND SAFETY OF GLIMEPIRIDE, EMPAGLIFLOZIN AND SITAGLIPTIN WITH METFORMIN IN TYPE 2 DIABETES MELLITUS: A DOUBLE AND TRIPLE DRUG THERAPY DR SAIMA CHANDIO (06-115232-001) Type 2 diabetes mellitus (T2DM) is a growing global health challenge, imposing significant disease burden and economic strain. In Pakistan, the situation is particularly alarming. According to the most recent IDF Atlas (2025), approximately 34.5 million adults (aged 20–79 years) are affected in Pakistan, with an age-standardized prevalence of 31.4%, the highest in the world. This escalating prevalence underscores the urgent need for effective treatment strategies tailored to the local population. The present study was designed to evaluate and compare the clinical efficacy and safety profiles of initial double and triple combination regimens in treatment-naïve patients with T2DM. After obtaining approval from the Institutional Review Board of Bahria University Health Sciences, Karachi (IRB- BUHSCK), this open-labeled, parallel-arm, randomized clinical trial was conducted at the Diabetic Clinic of the National Medical Center, Karachi. A total of 172 diagnosed type 2 diabetic patients (males and females, aged 30–55 years) meeting inclusion criteria were enrolled through randomization via the sealed-envelope method. Participants were allocated into four parallel treatment arms 43 in each: Group A received Metformin 500 mg + Glimepiride 2 mg (fixed-dose combination, FDC); Group B received Metformin 500 mg + Empagliflozin 12.5 mg (FDC); Group C received Metformin 500 mg + Sitagliptin 50 mg (FDC); and Group D received Metformin 500 mg + Empagliflozin 12.5 mg (FDC) + Sitagliptin 50 mg once daily, in addition to lifestyle modifications. 150 patients successfully completed the study (Group A: 34; Group B: 38; Group C: 37; Group D: 41). Of 90 days, with assessments at baseline, day 45, and day 90. The primary endpoint was a reduction in HbA1c of at least ≥1% from baseline to day 90, while secondary outcomes included changes in fasting and random blood sugar, body weight, and lipid profile. Safety outcomes were evaluated through hematological, hepatic, renal, and cardiovascular profiles, while adverse effects were also monitored. Results demonstrated that all four groups achieved statistically significant glycemic improvement (p < 0.001). The greatest HbA1c reduction was observed in Group D (–1.57%), followed by Group A (–1.34%), Group B (–1.11%), and Group C (– 1.00%). Participants maintained self-monitoring weekly diaries, and assessments was done on week 6 and 12. It was hypothesized that initial triple therapy would viii achieve superior glycemic reduction and metabolic benefits compared with double- drug combinations. The triple combination (Group D: metformin + empagliflozin + sitagliptin) provided the most comprehensive benefits, improving anthropometric, glycemic, lipid, hepatic, and renal parameters. Among the dual regimens, Group A (metformin + glimepiride) achieved superior glycemic control with modest lipid improvements, while Group B (metformin + empagliflozin) was more effective for weight and triglyceride reduction with favorable effects on HDL and renal function. Group C (metformin + sitagliptin) showed the least efficacy but remained well tolerated. Overall, treatment effects followed: Group D > Group A ≈ Group B > Group C, confirming triple therapy as the most balanced strategy while dual therapies offer targeted benefits that can be individualized Supervised by Prof. Dr. Nasim Karim 2025-12-01T00:00:00Z http://hdl.handle.net/123456789/19076 COMPARATIVE STUDY OF LAMA PLUS LABA WITH ATORVASTATIN AND PANAX GINSENG ALONE AND IN COMBINATION IN COPD PATIENTS TO IMPROVE PULMONARY FUNCTIONS DR. SAMEERA PERVAIZ 06-115222-001 Chronic obstructive pulmonary disease (COPD) is a debilitating disease characterized by progressive airflow obstruction. The cornerstones of treatment are bronchodilator drugs of two different classes including beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long-acting beta agonists (LABAs) and long-acting muscarinic antagonists (LAMAs) in combination. In COPD statins reduce neutrophil influx within lungs. Panax ginseng lowers oxidative stress and suppresses cytokine pro-inflammatory mediators potentially responsible for COPD. The objective of this study was to evaluate the efficacy and safety profile of statins and panax ginseng alone and in combination with LABA and LAMA, for COPD patients. The study was conducted at National Medical Centre in 162 patients. The patients were randomly divided into three groups, each containing 54 patients. The study period were 12 weeks with follow up of patients. Baseline investigations were carried out including ESR, blood CP, blood urea, serum creatinine, serum uric acid, LFTs (SGPT and bilirubin) blood glucose and pulmonary function tests including spirometry. At baseline, no significant differences were observed between groups for Forced Expiratory Volume in 1 second (FEV1), Forced Vital Capacity (FVC), or Peak Expiratory Flow Rate (PEFR). By week 4, significant improvements were observed for treatments B and C. FEV1 increased in treatment B (62.71 ± 4.12) and C (64.56 ± 3.13) compared to A (61.12 ± 3.91), with treatment C showing a greater improvement (p = 0.035). These trends continued through week 12, where treatment C (67.89 ± 3.49) consistently outperformed A (62.19 ± 3.45) and B (63.45 ± 5.12). FVC results followed a similar pattern, with treatment B (63.45 ± 5.12) and C (67.89 ± 3.49) outperforming A (62.19 ± 3.45) by week 12. PEFR improved most significantly for treatment C (377.69 ± 30.66) compared to B (366.48 ± 27.68) and A (348.15 ± 24.11). Inflammatory markers such as CRP and ESR decreased significantly, particularly for treatment C, where CRP dropped to 1.83 ± 2.89 and ESR to 11.11 ± 4.34 by week 12, indicating reduced inflammation. Treatment C showed the best overall outcomes across all parameters. viii In conclusion, the clinical efficacy of statins and panax ginseng in COPD patients, in combination with LABA and LAMA, is comparatively more escalated and with less adverse effects in comparison to statins and panax ginseng being used alone in COPD patients. Supervised by Dr. Khalid Mustafa Memon 2024-11-01T00:00:00Z http://hdl.handle.net/123456789/16868 COMPARISON OF EMPAGLIFLOZIN-LINAGLIPTIN WITH EMPAGLIFLOZIN- METFORMIN COMBINATION THERAPY IN REDUCTION OF BODY WEIGHT IN T2DM DR. NABILA RAFI 06-115212-001 Diabetic patients need the rational approaches that can provide in order to design an effective treatment plan against increase weight gain. Combinations of anti-diabetic medications may assist diabetic patients in selecting the optimal treatment for their condition. To determine the most effective anti-diabetic drug combinations for the treatment of diabetes along with its complications like nephropathy, retinopathy, and neuropathy and increase body mass index, one of the most pressing public health issues of the twenty-first century. Therefore the aim of the present study was to compare empagliflozin-linagliptin with empagliflozin- metformin combination for the reduction of body weight in T2DM. The current randomized control trial was conducted in National Medical Center, Karachi from December 2022 to February 2023. Total 200 diagnosed patients of type 2 diabetes mellitus was enrolled in which 100 were male and 100 were females. The patients were divided two groups on the basis of their treatment option; group A Empagliflozin with metformin and group B Empagliflozin with linagliptin. All the basic information of patients (such as name, age (years), sex (male / female), co-morbidities (cancer, trauma, hepatic impairment, renal dysfunction, cardiovascular events and many others), body mass index, glycated hemoglobin (HbA1c), RBS, LFT, RFT, Urea, creatinine, ketonuria, glucosuria, and pus cell were identified. For the analysis, descriptive statistics were calculated using SPSS version 25. At the beginning of the trial, a body mass index (BMI), wasist to hip ratio (WHR) and waist circumference (WC) was identified to evaluate the prospective effect of the medicines on weight reduction in diabetic patients. All the above parameters were approximately similar between patients of each group. At the end of 4th and 12th week, the difference in BMI, WHR and WC was identified between group A male with group B male and vice versa. The analysis shown the significant differences between groups. Moreover, group A has shown more decrease in anthropometric parameters as compared to group B. The more prominent difference was found in week 12. Moreover, the HbA1c, FBS and RBS were exhibited a degree of similarity among patients in each respective group. At the end of the 4th and 12th weeks, a discernible contrast in HbA1c, FBS and RBS was observed between male/female participants in group A and those in group B. The analysis has demonstrated statistically significant differences between the groups. Furthermore, it has been observed that both the groups exhibited a greater outcome to control glucose. A significant difference was observed during the 12th week. Moreover, the safety profile was evaluated, the average of lipid profile, liver enzymes, pancreatic enzymes, of Group A and B were found approximately similar and under normal range. In conclusion, in the treatment of weight gain, it has been determined that combination of Tab Empagliflozin with Tab Metformin is more effective than combination of Tab Empagliflozin with Tab Linagliptin. Moreover, the use of combination of Tab Empagliflozin with Tab Metformin led to an improvement in the quality of life of the patient, and both combinations had better outcomes in terms of the safety profiles of diabetic patients Aupervised by Prof,Dr.Khalid Mustafa Memon 2023-10-01T00:00:00Z http://hdl.handle.net/123456789/16867 CLINICAL EFFICACY AND SAFETY OF METFORMIN VERSUS APPLE CIDER VINEGAR (ACV) IN PREDIABETICS DR.SHIZMA JUNEJO (06-115212-003) Prediabetes is defined as a state of abnormal glucose homeostasis where blood glucose levels are elevated above normal, but not as high as those required for diagnosis of diabetes. Usually there are no clinical features except overweight or obesity but it may be characterized by hyperglycemia, increased thirst and food intake, frequent urination, fatigue. etc. If kept un-checked it proceeds to development of type 2 diabetes. . Following registration with clinical trials.gov vide NCT number 05759442, a clinical trial was conducted after approval of ERC & FRC. The objectives of the study were (1) to evaluate and compare the clinical efficacy of metformin HCl versus apple cider vinegar (ACV) along with lifestyle modification of diet control and exercise in pre-diabetics and (2) to assess the adverse effects, safety profile and cost effectiveness of metformin and ACV in pre-diabetics. After approval of ERC and FRC screening of prediabetics was started. Males and females ,17-40 years of age as per ADA 2010 and ISPAD 2018 criteria, were then enrolled following written informed consent. The subjects were randomized by computer generated list into Group A (control)being given (N=25, tablet Metformin HCl, 500 mg orally BD and Group B given (N=25, Apple cider vinegar 15 ml diluted in 200 ml water with dinner) for 12 weeks after excluding the 1st week of study due to escalation dose strategy. Both groups were kept on lifestyle modifications, including diet control and exercise alongside the treatment. Subjects were evaluated at baseline, week 6 and 12 for Anthropometric and Physiological parameters (Weight, Height, BMI, Waist circumference, Hip circumference, Waist hip ratio, Neck circumference, Blood pressure, Acanthosis nigricans). Metabolic parameters (HbA1c, FBG, Lipid profile) and Safety profile (CBC, SGOT, Serum Creatinine) were evaluated at baseline & week 12. Blood group was determined at baseline only while adverse effects were evaluated at 6 and 12 weeks. Cost effectiveness was evaluated at the end of study. Majority of participants were in age group 32 to 40 years. Blood group AB was found to be the commonest. In group A, the reduction in weight, HBA1c, FBG, HDL, was highly significant when day 0 values were compared with week 12. In group B, highly significant reduction resulted in weight, BMI, waist circumference, hip circumference, FBG, HDL with significant viii reduction in waist hip ratio and triglycerides with no effect on the neck circumference. Parameters for safety profile showed non-significant results in both groups for day 0 & week 12 indicating metformin and ACV being safe in the dose and for duration used. Metformin has exerted significant reducing effects on weight, HbA1c and FBG while apple cider vinegar has shown significant reduction in weight and FBG only.Study concluded that clinical efficacy of metformin is superior than the apple cider vinegar in prediabetics. Both drugs are found to be safe and no adverse effect in either group was reported , furthermore. Metformin is far more cost effective than apple cider vinegar Supervised by Prof,Dr.Nasim Karim 2023-10-01T00:00:00Z