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INDEX SR.NO. TITLE PAGE. NO. 1. Introduction to diabetes 1.1 Diabetes – as diseases 1.2 Various types of diabetes 1.3 Causes and symptoms of diabetes 1.4 Various treatment according to different routes 2. Introduction to metformin 2.1 Advantages and disadvantages of metformin 2.2 Detail study on main disadvantage of metformin 3. What are conjugates? 3.1 How to make conjugates? 3.2 Detail study on combining conjugate with metformin 4. Research methodology 5. Result and Discussion 6. Conclusion.

INTRODUCTION 1.1 DIABETES AS DISEASES Diabetes mellitus, often known simply as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough insulin, or the cells of the body becoming unresponsive to the hormone's effects. Diabetes accounts for approximately 4.2 million deaths every year, with an estimated 1.5 million caused by either untreated or poorly treated diabetes. 1.2 VARIOUS TYPES OF DIABETES 1. Type 1 Diabetes (T1D): An autoimmune disease where the pancreas stops producing insulin. 2. Type 2 Diabetes (T2D): The body becomes resistant to insulin, leading to high blood sugar. 3. Gestational Diabetes (GDM): Develops during pregnancy, usually in the second or third trimester. 1. LADA (Latent Autoimmune Diabetes in Adults): A form of T1D that develops in adults. 4. LADA (Latent Autoimmune Diabetes in Adults): A form of T1D that develops in adults 5. MODY (Maturity-Onset Diabetes of the Young): A genetic form of diabetes affecting young people. 6. Secondary Diabetes: Caused by another medical condition or treatment (e.g., pancreatitis, steroids)..

7. Monogenic Diabetes: Caused by a single genetic mutation (e.g., Wolfram syndrome). 8. Cystic Fibrosis-Related Diabetes (CFRD): Develops in people with cystic fibrosis. 9. Pancreatic Diabetes: Caused by pancreas damage or disease. 10. Steroid-Induced Diabetes: Caused by long-term steroid use. 1.3 CAUSES AND SYMPTOMS OF DIABETES • CAUSES 1. Genetics 2. Obesity 3. Physical inactivity 4. Age (45+) 5. Family history 6. Ethnicity (African American, Hispanic, Native American) 7. Previous gestational diabetes 8. Polycystic ovary syndrome (PCOS) 9. High blood pressure 10. High cholesterol.

• SYMPTOMS 1. Increased thirst and urination 2. Fatigue 3. Blurred vision 4. Slow healing of cuts and wounds 5. Tingling or numbness in hands/feet 6. Recurring skin infections 1.3 VARIOUS TREATMENT THROUGH DIFFERENT Oral Medications (T2D) 1. Metformin: First-line treatment (Glucophage) 2. Sulfonylureas: Stimulate insulin release (Glyburide, Glipizide) 3. Meglitinides: Stimulate insulin release (Repaglinide, Nateglinide) 4. Thiazolidinediones: Improve insulin sensitivity (Pioglitazone) 5. DPP-4 inhibitors: Block glucose release (Sitagliptin, Sax gliptin) ROUTES ORAL INJECTABLE.

6. SGLT2 inhibitors: Block glucose reabsorption (Canagliflozin, Empagliflozin) 7. Alpha-glucosidase inhibitors: Delay carbohydrate absorption (Acarbose) Injectables (T1D, T2D) 1. Insulin: Various types (Rapid-acting, Short-acting, Intermediate- acting, Long-acting) 2. GLP-1 receptor agonists: Enhance insulin secretion (Exenatide, Liraglutide) 3. Amylin analogs: Delay gastric emptying (Pramlintide) Combination Therapies 1. Metformin + Sulfonylurea: Improve insulin secretion and sensitivity. 2. Metformin + DPP-4 inhibitor: Enhance insulin secretion and sensitivity. 3. Insulin + GLP-1 receptor agonist: Improve glycemic control..

What is Metformin? Metformin is an oral anti-diabetic medication that belongs to the biguanide class. It is primarily used to treat type 2 diabetes mellitus. How Does Metformin Work? Metformin works by: 1. Decreasing glucose production in the liver 2. Increasing insulin sensitivity 3. Enhancing glucose uptake in muscles 4. Reducing glucose absorption from the gut Advantages and Disadvantages of metformin Advantages: 1. Effective glucose control 2. Weight-neutral 3. Low risk of hypoglycemia 4. Cardiovascular benefits 5. Affordable 6. Anti-PCOS effects 7. Anti-cancer properties.

Disadvantages: 1. Gastrointestinal side effects/Stomach disturbance 2. Lactic acidosis risk 3. Vitamin B12 deficiency 4. Kidney function concerns 5. Increased infection risk 6. Headaches and fatigue 7. Interactions with other medications Detail study on main disadvantage of metformin So, here the main disadvantage or side effect cause due to metformin is stomach disturbance. Stomach disturbances, also known as gastrointestinal (GI) disorders or dyspepsia, refer to a range of symptoms and conditions affecting the stomach and digestive system. So, to cure or reduce that side effect we will combine conjugates with metformin. Conjugates, specifically probiotic conjugates, have shown potential in mitigating stomach disturbances caused by metformin..

WHAT ARE CONJUGATES? Conjugates refer to compounds formed by linking two or more distinct molecules or entities to create a new therapeutic agent. Conjugates aim to enhance the efficacy, safety, and delivery of medications. Conjugates have revolutionized medicine by enabling targeted and efficient delivery of therapeutic agents. HOW ARE CONJUGATES FORM? Conjugates are formed through various chemical and biological methods, depending on the type of conjugate and its intended application Chemical Conjugation Methods 1. Amide Bond Formation: React metformin with a compound containing a carboxyl group (-COOH) using EDC (1-Ethyl-3- (3dimethylaminopropyl) carbodiimide) and NHS (N-Hydroxy succinimide). 2. Ester Bond Formation: React metformin with a compound containing a hydroxyl group (-OH) using EDC and NHS. 3. Thiol-Maleimide Conjugation: React metformin with a compound containing a thiol group (-SH) using maleimide. Biological Conjugation Methods 1. Enzymatic Conjugation: Use enzymes like transglutaminase to conjugate metformin to proteins or peptides. 2. Chemoenzymatic Conjugation: Combine chemical and enzymatic methods..

Conjugation Reactions 1. Metformin-Aluminum Hydroxide Conjugate: React metformin with aluminum hydroxide in water. 2. Metformin-Polymer Conjugate: React metformin with polymers like PEG or PLA. 3. Metformin-Protein Conjugate: React metformin with proteins like albumin or gelatin. 4. Metformin-Lipid Conjugate: React metformin with lipids like phospholipids. IS IT POSSIBLE TO MAKE CONJUGATES WITH ALUMINIUM HYDROXIDE AND MAGNESIUM HYDROXIDE? Yes, it's possible to make conjugates of metformin with aluminum hydroxide and magnesium hydroxide with using simethicone as a lubricant. METHODOLOGY Step 1: Materials Preparation - Al (OH)₃ - Mg (OH)₂ - Metformin HCl - Simethicone - Microcrystalline cellulose.

- Magnesium stearate - Silicon dioxide Step 2: Conjugate Preparation - Mix Al (OH)₃ & Mg (OH)₂ (1:1) - Add metformin HCl - Stir & dry under vacuum Step 3: Formulation Development - Tablet: Conjugate (85% w/w), Simethicone (2% w/w) - Capsule: Conjugate (90% w/w), Simethicone (3% w/w) Step 4: Simethicone Addition - Mix simethicone with conjugate & excipients Step 5: Tablet/Capsule Manufacture - Direct compression or wet granulation Step 6: Quality Control - FTIR, XRD, SEM, EDS Step 7: Stability Studies - Accelerated & long-term stability testing Step 8: Regulatory Compliance - FDA-approved, ICH guidelines.