Prediabetes Market Demand By Drug Class, Age Group, Region And Forecast To 2030: Grand View Research Inc.

San Francisco, 28 May 2024: The Report Prediabetes Market Size, Share & Trends Analysis Report By Drug Class (Diguanide, Thiazolidinediones), By Age Group (Children, Adult), By Region, And Segment Forecasts, 2024 – 2030 The global prediabetes market size is anticipated to reach USD 323.83 million by 2030 and it is projected to grow at a CAGR of 7.21% from 2024 to 2030, according to a new report…

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Addressing Hormonal Imbalances: Polycystic Ovarian Syndrome - Drug Pipeline Landscape

Polycystic Ovarian Syndrome (PCOS) is a common endocrine disorder that affects millions of women worldwide. Characterized by hormonal imbalances, irregular menstrual cycles, and cysts on the ovaries, Polycystic Ovarian Syndrome (PCOS) can have a significant impact on reproductive health, fertility, and overall well-being. While lifestyle modifications and conventional treatments such as birth control pills and insulin-sensitizing medications are commonly used to manage symptoms, there remains a need for more targeted and efficacious therapies to address the underlying hormonal dysregulation associated with PCOS. In this article, we explore the drug pipeline landscape for Polycystic Ovarian Syndrome (PCOS), highlighting promising therapies and innovations aimed at improving outcomes for patients.

The treatment landscape for PCOS is evolving rapidly, driven by advances in understanding the complex pathophysiology of the disorder and the development of novel therapeutic approaches to address its underlying hormonal imbalances. Central to the pathogenesis of PCOS are disturbances in ovarian function, insulin resistance, and hyperandrogenism, which contribute to the hallmark features of the syndrome, including irregular menstrual cycles, anovulation, and hirsutism.

One area of active research in PCOS therapeutics is the development of drugs targeting insulin resistance and hyperinsulinemia, which are commonly observed in women with PCOS and are believed to play a central role in the pathogenesis of the disorder. Insulin-sensitizing agents such as metformin and thiazolidinediones have been shown to improve menstrual regularity, ovulation, and metabolic parameters in women with PCOS. However, newer agents with improved efficacy and fewer side effects are being investigated, including novel insulin sensitizers, glucagon-like peptide-1 (GLP-1) receptor agonists, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors.

Request the sample copy of report @ https://www.globalinsightservices.com/request-sample/GIS31256

Additionally, targeting hyperandrogenism, or elevated levels of male hormones such as testosterone, is a key therapeutic strategy in PCOS. Anti-androgen medications such as spironolactone and cyproterone acetate are commonly used to manage hirsutism and acne in women with PCOS. However, these medications are associated with side effects and may not be suitable for all patients. Novel anti-androgen therapies, including selective androgen receptor modulators (SARMs) and 5-alpha reductase inhibitors, are currently under investigation for their potential to safely and effectively reduce androgen levels and improve symptoms of hyperandrogenism in women with PCOS.

Furthermore, targeting ovarian function and ovulation is a central focus of PCOS therapeutics, particularly for women seeking to achieve pregnancy. While traditional ovulation induction agents such as clomiphene citrate and letrozole are commonly used in women with PCOS, newer treatments such as gonadotropin-releasing hormone (GnRH) antagonists and kisspeptin analogs are being explored for their potential to improve ovulation rates and pregnancy outcomes in this population.

In conclusion, the drug pipeline landscape for PCOS is characterized by ongoing research and innovation aimed at addressing the underlying hormonal imbalances and associated symptoms of the disorder. While challenges remain in translating preclinical findings into safe and effective treatments, the progress made in understanding the pathophysiology of PCOS and the development of targeted therapeutics offers hope for improved outcomes and quality of life for women affected by this complex endocrine disorder. As research continues to advance and clinical trials progress, the future holds promise for more personalized and effective treatments that can address the diverse needs of patients with PCOS.

Anti-diabetic Medication Market is Set To Fly High in Years to Come

Global Anti-diabetic Medication Market Report from AMA Research highlights deep analysis on market characteristics, sizing, estimates and growth by segmentation, regional breakdowns & country along with competitive landscape, player’s market shares, and strategies that are key in the market. The exploration provides a 360° view and insights, highlighting major outcomes of the industry. These insights help the business decision-makers to formulate better business plans and make informed decisions to improved profitability. In addition, the study helps venture or private players in understanding the companies in more detail to make better informed decisions. Major Players in This Report Include, AstraZeneca plc (United Kingdom), Bayer AG (Germany), C.H. Boehringer Sohn AG & Ko. KG (Germany), Bristol-Myers Squibb (United States), Eli Lilly (United States), Halozyme Therapeutics (United States), Johnson & Johnson (United States), Merck & Co. Inc. (United States), Novartis AG (Switzerland), Pfizer Inc. (United States). Free Sample Report + All Related Graphs & Charts @: https://www.advancemarketanalytics.com/sample-report/162818-global-anti-diabetic-medication-market Anti-diabetic medications are medicines developed to stabilize and control blood glucose levels amongst people with diabetes. Anti-diabetic medications are commonly used to manage diabetes. Anti-diabetic medications are all pharmacological agents that have been approved for hyperglycemic treatment in diabetes mellitus. The increasing prevalence of diabetes across the globe will stimulate the market potential for anti-diabetic medication during the forecast period. Market Drivers

Rising Prevalence of Chronic Diseases like Diabetes across the Globe

Growing Prevalence of Lifestyle-Induced Disorders such as Obesity

Market Trend

Increasing Adoption of Oral Antidiabetic Drugs

Opportunities

Rising Spending on Research and Development for Innovative Drugs

Challenges

Safety Issues Pertaining to Some Diabetic Drugs

Enquire for customization in Report @: https://www.advancemarketanalytics.com/enquiry-before-buy/162818-global-anti-diabetic-medication-market In this research study, the prime factors that are impelling the growth of the Global Anti-diabetic Medication market report have been studied thoroughly in a bid to estimate the overall value and the size of this market by the end of the forecast period. The impact of the driving forces, limitations, challenges, and opportunities has been examined extensively. The key trends that manage the interest of the customers have also been interpreted accurately for the benefit of the readers. The Anti-diabetic Medication market study is being classified by Type (Insulin (Rapid acting analog, Long-acting analog, Premixed insulin, Short-acting analog, and Intermediate-acting insulin), Drug class (Alpha glucosidase inhibitors, Biguanides, Sulphonylureas, GLP-1 (Glucagon-like peptide) agonists, DPP-IV (Dipeptidyl Peptidase) inhibitors, Meglitinides, SGLT-II (Sodium-Glucose Transport Proteins) inhibitors, and Thiazolidinedione)), Application (Prevent and Treatment Diabetes, Obesity Treatment, Cardiovascular Protection, Others), Route of Administration (Insulin Syringe/ Insulin Pen, Insulin Pump, Intravenous Infusion, Oral, Others), End User (Pediatric, Adult, Geriatric) The report concludes with in-depth details on the business operations and financial structure of leading vendors in the Global Anti-diabetic Medication market report, Overview of Key trends in the past and present are in reports that are reported to be beneficial for companies looking for venture businesses in this market. Information about the various marketing channels and well-known distributors in this market was also provided here. This study serves as a rich guide for established players and new players in this market. Get Reasonable Discount on This Premium Report @ https://www.advancemarketanalytics.com/request-discount/162818-global-anti-diabetic-medication-market Extracts from Table of Contents Anti-diabetic Medication Market Research Report Chapter 1 Anti-diabetic Medication Market Overview Chapter 2 Global Economic Impact on Industry Chapter 3 Global Market Competition by Manufacturers Chapter 4 Global Revenue (Value, Volume*) by Region Chapter 5 Global Supplies (Production), Consumption, Export, Import by Regions Chapter 6 Global Revenue (Value, Volume*), Price* Trend by Type Chapter 7 Global Market Analysis by Application ………………….continued This report also analyzes the regulatory framework of the Global Markets Anti-diabetic Medication Market Report to inform stakeholders about the various norms, regulations, this can have an impact. It also collects in-depth information from the detailed primary and secondary research techniques analyzed using the most efficient analysis tools. Based on the statistics gained from this systematic study, market research provides estimates for market participants and readers. Contact US : Craig Francis (PR & Marketing Manager) AMA Research & Media LLP Unit No. 429, Parsonage Road Edison, NJ New Jersey USA – 08837 Phone: +1 201 565 3262, +44 161 818 8166 [email protected]

Why don't you try to say thiazolidinedione 3 times and maybe you'll calm down

What Are My Options for Type 2 Diabetes Medications?

There are different types, or classes, of medications that work in different ways to lower blood glucose (also known as blood sugar) levels. Some options are taken by mouth and others are injected. Some of the commonly used classes of non-insulin medications include:

Metformin

Dipeptidyl peptidase 4 (DPP-4) inhibitors

Glucagon-like peptide 1 (GLP-1) and dual GLP-1/gastric inhibitory peptide (GIP) receptor agonists

Sodium-glucose cotransporter 2 (SGLT2) inhibitors

Sulfonylureas

Thiazolidinediones (TZDs)

Metformin

Metformin (Glucophage) is classified as a biguanide medication and is the only available medication in this class. Metformin lowers blood glucose levels primarily by decreasing the amount of glucose produced by the liver. Metformin also helps lower blood glucose levels by making muscle tissue more sensitive to insulin so blood glucose can be used for energy.

It is usually taken two times a day. A side effect of metformin may be diarrhea, but this is improved when the drug is taken with food.

DPP-4 Inhibitors

DPP-4 inhibitors help improve A1C (a measure of average blood glucose levels over two to three months) without causing hypoglycemia (low blood glucose). They work by preventing the breakdown of naturally occurring hormones in the body, GLP-1 and GIP. These hormones reduce blood glucose levels in the body, but they are broken down very quickly so it does not work well when injected as a drug itself.

By interfering in the process that breaks down GLP-1 and GIP, DPP-4 inhibitors allow these hormones to remain active in the body longer, lowering blood glucose levels only when they are elevated. DPP-4 inhibitors do not cause weight gain and are usually very well tolerated.

There are four DPP-4 inhibitors currently on the market in the U.S.:

Alogliptin (Nesina)

Linagliptin (Tradjenta)

Saxagliptin (Onglyza)

Sitagliptin (Januvia)

GLP-1 and Dual GLP-1/GIP Receptor Agonists

As noted in the description for DPP-4 inhibitors, GLP-1 and GIP are natural hormones in the body that help maintain glucose levels. Use of GLP-1 and dual GLP-1/GIP receptor agonists is another strategy to help use these hormones to improve blood glucose management in people with type 2 diabetes.

These medications have similar effects to the GLP-1 and GIP produced in the body but are resistant to being broken down by the DPP-4 enzyme. These medications can result in large benefits on lowering blood glucose and body weight. Some agents in this class have also been shown to prevent heart disease. Most of these medications are injected, with the exception of one that is taken by mouth once daily, called semaglutide (Rybelsus).

Injectable GLP-1 receptor agonists currently on the market include:

Dulaglutide (Trulicity)

Exenatide (Byetta)

Exenatide extended-release (Bydureon)

Liraglutide (Victoza)

Lixisenatide (Adlyxin)

Injectable semaglutide (Ozempic)

One dual GLP-1/GIP receptor agonist is currently on the market called tirzepatide (Mounjaro). How often you need to inject these medications varies from twice daily to once weekly, depending on the medication. The most common side effect with these medications is nausea and vomiting, which is more common when starting or increasing the dose.

SGLT2 Inhibitors

Glucose in the bloodstream passes through the kidneys where it can either be excreted in the urine or reabsorbed back into the blood. Sodium-glucose cotransporter 2 (SGLT2) works in the kidney to reabsorb glucose. A new class of medication, SGLT2 inhibitors, block this action, causing excess glucose to be eliminated in the urine.

By increasing the amount of glucose excreted in the urine, people can see improved blood glucose, some weight loss, and small decreases in blood pressure. Bexagliflozin (Brenzavvy), canagliflozin (Invokana), dapagliflozin (Farxiga), and empagliflozin (Jardiance) are SGLT2 inhibitors that have been approved by the Food and Drug Administration (FDA) to treat type 2 diabetes. SGLT2 inhibitors are also known to help improve outcomes in people with heart disease, kidney disease, and heart failure.

For this reason, these medications are often used in people with type 2 diabetes who also have heart or kidney problems. Because they increase glucose levels in the urine, the most common side effects include genital yeast infections.

Sulfonylureas

Sulfonylureas have been in use since the 1950s and they stimulate beta cells in the pancreas to release more insulin. There are three main sulfonylurea drugs used today, glimepiride (Amaryl), glipizide (Glucotrol and Glucotrol XL), and glyburide (Micronase, Glynase, and Diabeta). These drugs are generally taken one to two times a day before meals.

All sulfonylurea drugs have similar effects on blood glucose levels, but they differ in side effects, how often they are taken, and interactions with other drugs. The most common side effects with sulfonylureas are low blood glucose and weight gain.

TZDs

Rosiglitazone (Avandia) and pioglitazone (Actos) are in a group of drugs called thiazolidinediones. These drugs help insulin work better in the muscle and fat and reduce glucose production in the liver.

A benefit of TZDs is that they lower blood glucose without having a high risk for causing low blood glucose. Both drugs in this class can increase the risk for heart failure in some individuals and can also cause fluid retention (edema) in the legs and feet.

●Pathophysiology – Edema is a palpable swelling produced by expansion of the interstitial fluid volume. Generalized edema is produced by one or more of the following: increased capillary hydrostatic pressure, decreased capillary oncotic pressure, and/or increased capillary permeability. The retention of sodium and water by the kidneys must also occur for edema to develop.

●Evaluation of lower extremity edema – Our approach to the evaluation of leg edema in adults depends upon whether the patient has unilateral/asymmetric edema or bilateral edema, and upon the acuity of the edema.

•Acute unilateral (or asymmetric) edema – In patients with acute unilateral or asymmetric edema, we first evaluate for deep vein thrombosis (DVT). If DVT has been excluded, we evaluate for other causes of acute unilateral or asymmetric edema:

Acute edema:

Medications

Heart failure

Nephrotic syndrome

Venous thrombosis

Acute worsening of chronic causes

Chronic edema:

Venous insufficiency

Heart failure

Left-sided with preserved or reduced ejection fraction

Right-sided

Pulmonary hypertension (including sleep apnea)

Restrictive pericarditis

Restrictive cardiomyopathy

Renal disease (including nephrotic syndrome)

Liver disease (early cirrhosis)

Premenstrual edema

Pregnancy

Malnutrition (including malabsorption and protein losing enteropathy)

Pelvic compression (including tumor or lymphoma)

Dependent edema

Sodium or fluid overload (including parenteral fluids, antibiotics and other drugs with large amounts of sodium)

Refeeding edema

Idiopathic edema

Inflammation (including sepsis)

Medications

Chronic lymphedema:

Primary lymphedema (presenting in childhood)

Secondary lymphedema (including lymph node dissection)

Thyroid disease (myxedema)

•Chronic unilateral (or asymmetric) edema – In patients with chronic unilateral or asymmetric edema, a diagnosis can generally be made based upon clinical features. If the history and examination are not consistent with a particular diagnosis (eg, venous insufficiency, lymphedema, or complex regional pain syndrome), we obtain compression ultrasonography (CUS) with Doppler. If the CUS suggests pelvic outflow obstruction, we obtain a transvaginal ultrasound or a contrast-enhanced computed tomography (CT) scan of the pelvis.

•Acute bilateral edema – In patients with acute bilateral leg edema, we first evaluate for DVT. If DVT has been excluded, we assess for edema as a medication side effect (table 3) or as a manifestation of acute heart failure or acute nephrotic syndrome (table 2).

Table 3: DHP calcium channel blockers (e.g., amlodipine), other vasodilators:

Hydralazine

Minoxidil

Alpha-blockers

Endocrine:

Thiazolidinediones

Rosiglitazone

Pioglitazone

Glucocorticoids

Fludrocortisone

Estrogen

Progesterone

Tamoxifen

Aromatase inhibitors

Testosterone

Androgens

Less common meds:

Non-DHP calcium channel blockers (verapamil and diltiazem), anticonvulsants:

Gabapentin

Pregabalin

Antineoplastic:

Docetaxel

Cisplatin

Interleukin 2 therapy

Antiparkinson:

Pramipexole

Ropinirole

Antidepressants:

Monoamine oxidase inhibitors

Trazodone

Other:

Diazoxide

NSAIDs

Proton pump inhibitors 

•Chronic bilateral edema – In patients with chronic bilateral leg edema, a diagnosis can often be made based upon clinical features. If the history and examination are not consistent with a particular diagnosis (eg, chronic venous disease, heart failure, pulmonary hypertension, renal, or liver disease), we obtain a semiquantitative urine dipstick for protein and measure serum creatinine, serum albumin, prothrombin time, liver function tests, and thyroid-stimulating hormone. If those tests are unrevealing, we obtain an echocardiogram. If the echocardiogram does not suggest the etiology of the edema, and chronic venous disease does not seem likely, we obtain imaging of the pelvis to exclude venous outflow obstruction.

●Evaluation of upper extremity edema – Our approach to the differential diagnosis of arm edema in adults depends upon the acuity of the edema.

•Acute – Acute isolated upper extremity edema can be caused by trauma, infection, superficial thrombophlebitis, or inflammatory arthritis of the upper extremity. Upper extremity venous thrombosis should be suspected when none of the etiologies noted above are present or if there are other significant risk factors such as the presence of a venous catheter. CUS with Doppler is the study of choice for the initial evaluation of patients with possible upper extremity venous thrombosis.

•Subacute/chronic – More gradual swelling of the arm occurs with lymphedema.

●Pulmonary edema – Patients with pulmonary edema complain primarily of shortness of breath and orthopnea. Physical examination usually reveals a tachypneic patient with rales and possibly a diastolic gallop (S3). The diagnosis of pulmonary edema should be confirmed by radiologic studies because other disorders, such as a pulmonary embolus, may produce similar symptoms but will require different therapy.

●Ascites – Ascites is associated with abdominal distention and both shifting dullness and a fluid wave on percussion of the abdomen. If ascites is suspected, the diagnosis can be confirmed by ultrasonography.

●Other presentations of edema – Other forms of edema include lymphedema, myxedema, periorbital edema, and scrotal edema.

Mastering the Complex Maze: Navigating Type 2 Diabetes with Medvantage's Advanced Certification

Introduction:

Type 2 Diabetes Mellitus (T2DM) stands as a formidable challenge in the realm of healthcare, marked by its intricate pathophysiology and the far-reaching implications it holds for affected individuals. The Advanced Certificate in Diabetes Mellitus, offered by Medvantage, serves as a beacon of knowledge, equipping healthcare professionals with in-depth insights into T2DM. This article explores the program's focus on pathophysiology, clinical manifestations, diagnostic criteria, and evidence-based management strategies.

Pathophysiology of T2DM in Advanced Certificate in Diabetes Mellitus

1.Insulin Resistance: The foundation of T2DM lies in peripheral insulin resistance, where vital tissues—skeletal muscle, adipose tissue, and the liver—show diminished responsiveness to insulin. This disruption hampers glucose uptake and utilization, forming a key focus in the program's curriculum.

2.Beta-Cell Dysfunction: A progressive decline in pancreatic beta-cell function exacerbates hyperglycemia. Genetic factors, chronic inflammation, and metabolic stress contribute to the deterioration of insulin-secreting beta cells.

3.Adipose Tissue Dysregulation: Obesity-induced dysfunction in adipose tissue triggers an inflammatory milieu, releasing adipokines and free fatty acids. These factors intricately contribute to insulin resistance and disrupted glucose homeostasis, an aspect thoroughly explored in the advanced curriculum.

Clinical Manifestations:

1.Polyuria, Polydipsia, Polyphagia: The classical symptoms of T2DM find their roots in hyperglycemia-induced osmotic diuresis. It delves into the intricacies of fluid loss, increased thirst, and excessive hunger as cardinal signs demanding clinical attention.

2.Fatigue and Malaise: The program underscores the link between inefficient glucose utilization and persistent fatigue, recognizing the clinical relevance of energy metabolism in T2DM.

3. Microvascular and Macrovascular Complications: The comprehensive care required for individuals with T2DM, shedding light on the microvascular complications (retinopathy, nephropathy, neuropathy) and macrovascular complications (cardiovascular disease) resulting from chronic hyperglycemia.

Diagnostic Criteria:

1.Fasting Plasma Glucose and Oral Glucose Tolerance Test: The Course emphasizes the importance of precise diagnostic criteria, including elevated fasting plasma glucose levels and abnormal oral glucose tolerance tests.

2.Hemoglobin A1c (HbA1c): With a focus on long-term glycemic control, the program recognizes HbA1c levels as pivotal diagnostic and monitoring tools in T2DM.

Management in Advanced Certificate in Diabetes Mellitus:

1.Lifestyle Modification: The role of lifestyle interventions—regular physical activity, weight management, and a balanced diet—as fundamental pillars in T2DM management, addressing both insulin resistance and beta-cell dysfunction.

2.Oral Antidiabetic Medications: The curriculum covers a spectrum of pharmacotherapy options, including metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 (DPP-4) inhibitors, each targeting specific aspects of T2DM pathophysiology.

3.Injectable Therapies: In advanced cases, the program explores the necessity of insulin therapy or glucagon-like peptide-1 (GLP-1) receptor agonists to optimize glycemic control.

4.Patient Education and Continuous Monitoring: Medvantage underscores the pivotal role of patient empowerment through education on self-monitoring, medication adherence, and lifestyle management for long-term success.

Conclusion:

The Advanced Certificate in Diabetes Mellitus provided by Medvantage represents a milestone in advancing expertise in T2DM. Through a multifocal approach and a deep understanding of pathophysiology, the program lays the foundation for evidence-based clinical practice. As research progresses, the personalized care plans and tailored therapeutic strategies fostered by the course provides hope for improved outcomes and an enhanced quality of life for individuals navigating the complexities of T2DM.

what is best medication for Type II diabetes

The choice of medication for Type 2 diabetes depends on various factors, including individual health conditions, lifestyle, and preferences. Different medications work in different ways to help manage blood sugar levels. It's essential to consult with a healthcare professional to determine the most suitable treatment plan. Here are some common types of medications used for Type 2 diabetes:

Metformin:

Often the first-line treatment for Type 2 diabetes.

Helps lower blood sugar by reducing glucose production in the liver.

Improves the body's sensitivity to insulin.

Sulfonylureas:

Stimulate the pancreas to release more insulin.

Include medications like glipizide, glyburide, and glimepiride.

Meglitinides:

Work similarly to sulfonylureas but have a shorter duration of action.

Stimulate insulin release from the pancreas.

Examples include repaglinide and nateglinide.

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors:

Increase insulin release and reduce glucagon levels.

Examples include sitagliptin, saxagliptin, and linagliptin.

Thiazolidinediones (TZDs):

Improve insulin sensitivity in the body's cells.

Medications like pioglitazone and rosiglitazone belong to this class.

SGLT2 Inhibitors:

Lower blood sugar levels by promoting the excretion of glucose through urine.

Examples include empagliflozin, canagliflozin, and dapagliflozin.

GLP-1 Receptor Agonists:

Increase insulin release and decrease glucagon levels.

Also, slow down digestion, leading to a feeling of fullness.

Include medications like liraglutide, exenatide, and dulaglutide.

Insulin:

Used when other medications are not sufficient to control blood sugar levels.

Comes in various types, including rapid-acting, short-acting, intermediate-acting, and long-acting insulin.

The best medication for Type 2 diabetes varies from person to person.  Jardiance 25 mg cnsumes all of the ingredients It's crucial to consider factors such as the individual's overall health, lifestyle, and potential side effects of the medications

Effective Allopathic Treatments for Diabetes: Regain Control of Your Health

In an era where lifestyle diseases are becoming increasingly prevalent, diabetes stands out as a significant concern. Characterized by high blood sugar levels, diabetes can lead to a range of complications if left unmanaged. Fortunately, medical science has made remarkable strides in developing effective treatments to manage diabetes, and one such approach is through allopathy.

Understanding Allopathy Treatment for Diabetes

Allopathy, also known as conventional or mainstream medicine, is a widely practiced approach to medical treatment that utilizes pharmaceuticals and other interventions to alleviate symptoms and manage health conditions. Allopathic treatments for diabetes are based on a thorough understanding of the disease's underlying mechanisms and aim to control blood sugar levels, prevent complications, and enhance overall quality of life for individuals living with diabetes.

Key Allopathic Treatments for Diabetes

Insulin Therapy: For individuals with type 1 diabetes, insulin therapy is a cornerstone of treatment. Insulin is a hormone responsible for regulating blood sugar levels, and in type 1 diabetes, the body doesn't produce enough insulin. Allopathic treatment involves administering insulin through injections or insulin pumps to maintain normal blood sugar levels.

Oral Medications: Allopathic medicine offers a variety of oral medications for managing type 2 diabetes, which primarily focus on improving insulin sensitivity, reducing glucose production in the liver, and increasing insulin secretion from the pancreas. Common classes of medications include metformin, sulfonylureas, thiazolidinediones, and DPP-4 inhibitors.

GLP-1 Receptor Agonists: These injectable medications help regulate blood sugar levels by increasing insulin secretion, slowing digestion, and reducing appetite. GLP-1 receptor agonists are particularly effective for individuals with type 2 diabetes who struggle with weight management.

SGLT2 Inhibitors: These medications lower blood sugar levels by preventing the kidneys from reabsorbing glucose and promoting its excretion through urine. SGLT2 inhibitors also offer additional benefits such as weight loss and cardiovascular protection.

Blood Pressure and Cholesterol Management: People with diabetes are at a higher risk of developing cardiovascular complications. Allopathy emphasizes managing blood pressure and cholesterol levels to reduce the risk of heart disease, stroke, and other related issues.

The Importance of Lifestyle Modifications

While allopathic treatments play a crucial role in diabetes management, they are most effective when complemented by healthy lifestyle changes. These include adopting a balanced diet rich in whole grains, lean proteins, fruits, and vegetables, engaging in regular physical activity, maintaining a healthy weight, managing stress, and getting adequate sleep. Lifestyle modifications can enhance the effectiveness of allopathic treatments, potentially reducing the need for higher medication doses.

Personalized Treatment Plans

Allopathic treatments for diabetes are not one-size-fits-all solutions. Healthcare providers tailor treatment plans based on individual factors such as the type of diabetes, overall health, age, and any existing complications. Regular monitoring of blood sugar levels, along with ongoing communication with healthcare professionals, ensures that treatment plans can be adjusted as needed to achieve optimal results.

Conclusion

Diabetes is a complex condition that requires comprehensive management. Allopathy offers a diverse range of treatments that address the various aspects of diabetes, from regulating blood sugar levels to preventing complications. However, it's important to remember that successful diabetes management also requires active participation in making healthy lifestyle choices. By combining effective allopathic treatments with positive lifestyle modifications, individuals with diabetes can regain control of their health and lead fulfilling lives. Always consult a healthcare professional before making any changes to your diabetes treatment plan.

Insulin Sensitizers Market Is Estimated To Witness High Growth Owing To Increasing Prevalence of Insulin Resistance

The global Insulin Sensitizers Market is estimated to be valued at US$ 15.09 billion in 2023 and is expected to exhibit a CAGR of 5.5% over the forecast period 2023-2030, as highlighted in a new report published by Coherent Market Insights. Market Overview: Insulin sensitizers are medications that help improve insulin sensitivity and reduce blood sugar levels in individuals suffering from insulin resistance. These drugs are primarily used in the treatment of type 2 diabetes and metabolic syndrome. Insulin resistance occurs when the body's cells become inefficient at using insulin, leading to high blood sugar levels. Insufficient insulin sensitivity can also result in other health complications such as obesity, hypertension, and cardiovascular diseases. Insulin sensitizers play a crucial role in managing insulin resistance by enhancing the body's response to insulin and facilitating glucose uptake by the cells. These medications help regulate blood sugar levels, decrease the risk of diabetes-related complications, and improve overall metabolic health. The growing prevalence of insulin resistance, coupled with the rising global burden of diabetes, is driving the demand for insulin sensitizers. Market Key Trends: One key trend observed in the insulin sensitizers market is the increasing focus on combination therapies. Healthcare providers are increasingly prescribing combination therapies that include insulin sensitizers along with other diabetes medications to achieve optimal glycemic control. The combination approach allows for better blood glucose management, reduced side effects, and improved patient adherence to treatment regimens. For example, a common combination therapy includes a sulfonylurea (such as glimepiride or glipizide) along with a thiazolidinedione (such as pioglitazone). The sulfonylurea stimulates insulin secretion from the pancreas, while the thiazolidinedione improves insulin sensitivity and reduces insulin resistance. This combination therapy offers a dual mechanism of action, resulting in better glycemic control in patients with type 2 diabetes. PEST Analysis: - Political: Government policies and regulations related to drug pricing and reimbursement can impact the insulin sensitizers market. Price controls or changes in reimbursement policies can affect the financial viability of manufacturers and influence market dynamics. - Economic: The growing healthcare expenditure, increasing disposable income, and rising healthcare awareness are favorable economic factors that contribute to the growth of the insulin sensitizers market. - Social: Lifestyle changes, sedentary behaviors, unhealthy dietary habits, and the high prevalence of obesity contribute to the rising incidence of insulin resistance and diabetes globally. - Technological: Advancements in drug delivery systems, such as insulin pens and pumps, have improved patient convenience and adherence to insulin sensitizers. Key Takeaways: 1: The Global Insulin Sensitizers Market Size is expected to witness high growth, exhibiting a CAGR of 5.5% over the forecast period. This growth is primarily driven by the increasing prevalence of insulin resistance and the rising global burden of diabetes. Insulin sensitizers play a crucial role in managing insulin resistance and improve overall metabolic health. 2: Regionally, North America is anticipated to be the fastest growing and dominating region in the insulin sensitizers market. The region's high prevalence of diabetes, well-established healthcare infrastructure, and favorable reimbursement policies contribute to its market dominance. 3: Key players operating in the global insulin sensitizers market include Eli Lilly and Company, Novo Nordisk, Sanofi, Merck & Co., Bristol Myers Squibb, AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, and Takeda Pharmaceutical. These companies focus on product innovation, strategic collaborations, and geographic expansion to gain a competitive edge in the market.

What Does Insulin Resistance Mean?

What Does Insulin Resistance Mean? https://blogdiabetes.com/blood-sugar Welcome to our channel, where we strive to provide you with accurate and reliable information about diabetes and related topics. In today's video, we will be delving into the concept of insulin resistance – a condition that affects millions of individuals worldwide. As a diabetes expert, I will guide you through the intricacies of insulin resistance, shedding light on its causes, symptoms, potential complications, and management strategies. Insulin resistance refers to a metabolic condition in which the body's cells become less responsive to the effects of insulin. Insulin, a hormone produced by the pancreas, plays a crucial role in regulating blood sugar levels. It facilitates glucose uptake by the cells, allowing them to utilize this essential energy source efficiently. However, when cells develop resistance to insulin, glucose fails to enter the cells effectively, leading to elevated blood sugar levels. In this video, we will explore the primary causes of insulin resistance. Genetic factors, sedentary lifestyle, poor dietary choices, excessive weight gain, and certain medical conditions like polycystic ovary syndrome (PCOS) and hypertension contribute to its development. By understanding these factors, individuals at risk can make informed decisions to prevent or manage the condition effectively. Recognizing the symptoms associated with insulin resistance is crucial for early detection and intervention. Fatigue, frequent urination, increased thirst, weight gain, and difficulty losing weight are some common signs to watch out for. Failure to address insulin resistance promptly can result in the progression to prediabetes or even type 2 diabetes, with potential complications such as cardiovascular disease, kidney problems, and nerve damage. Managing insulin resistance involves adopting a holistic approach. In this video, we will discuss dietary modifications, regular physical activity, and weight management techniques that can help improve insulin sensitivity. Additionally, we will explore the role of medications, such as metformin and thiazolidinediones, in managing insulin resistance. It is important to note that these medications should only be prescribed by a healthcare professional after a thorough evaluation. Moreover, we will delve into the significance of monitoring blood sugar levels, as well as the importance of routine check-ups to assess your overall health. Lifestyle changes, including a balanced diet rich in whole grains, fruits, and vegetables, coupled with regular exercise, can significantly improve insulin sensitivity and overall well-being. Join us in this enlightening video as we address the concerns surrounding insulin resistance, debunk common misconceptions, and provide practical strategies to manage this condition effectively. Remember, knowledge is empowering, and with the right information, you can take control of your health and prevent the progression of insulin resistance. Don't forget to hit the subscribe button and turn on notifications for more informative content on diabetes-related topics. Stay healthy, stay informed! =========================== Affiliate Disclaimer: While we receive affiliate compensation for reviews/promotions on this page, we always offer an honest opinion, relevant experiences and genuine views related to the product or service itself. Our goal is to help you make the best purchasing decisions, however, the views and opinions expressed are ours only. =========================== source https://www.youtube.com/watch?v=oZ2QKe0mrHc

Type 2 Diabetes Market – Unlocking Balance, Empowering Health: Transforming Type 2 Diabetes Care with Innovation

The Type 2 Diabetes Market Report assists in determining the optimum distribution methods for certain products as well as possible markets for future product launches. The report also analyses the purchase and supply trends that influence the market’s production strategy. The Type 2 Diabetes market research study is one of the most detailed market research reports available, highlighting the Type 2 Diabetes industry’s constraints, market trends, opportunities, driving factors, emerging trends, product types, applications, and competition.

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You can get insights into comprehensive TOC, Tables, and Charts presented throughout the report for valuable data, information, important statistics, trends, and detailed competitive landscape information in this market.

Type 2 Diabetes Market TOC: 

The following are the leading companies in the global Type 2 Diabetes market: 

Takeda Pharmaceutical Co. Ltd

Sanofi SA

Novo Nordisk AS

Novartis AG

Merck & Co. Inc

Eli Lilly and Co.

Daiichi Sankyo Co. Ltd

Boehringer Ingelheim International GmbH

AstraZeneca PLC

Amgen Inc.

Growth Plus Reports analyses the important trends in each segment and sub-segment of the Type 2 Diabetes market, as well as forecasts at the global and regional levels from 2023 to 2031. The market has been segmented in our report based on product type and application.

SEGMENTS

GLOBAL TYPE 2 DIABETES MARKET – ANALYSIS & FORECAST, BY DRUG CLASS

Sulfonylureas

Meglitinide/Phenylalanine Analogues

Glucagon-like Peptide-1 (GLP-1) Receptor Agonists

Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

Biguanide (AMPK Activator)

Thiazolidinediones (PPARγ Activator)

Others (α-Glucosidase Inhibitors, Amylin Analogues, Dopamine-D2 Receptor Agonists, Sodium-glucose Cotransport-2 (SGLT-2) Inhibitors, etc.)

GLOBAL TYPE 2 DIABETES MARKET – ANALYSIS & FORECAST, BY DISTRIBUTION CHANNEL

Hospital Pharmacies

Retail Pharmacies

Online Pharmacies

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Businesses can use Type 2 Diabetes market reports to learn more about market drivers and market limitations, which can help them decide whether to reduce or increase the production of a specific product. As globalization increases, many organizations require global market research that includes practical market data to improve strategic planning. This global Type 2 Diabetes market report analyses key market dynamics and provides comprehensive statistics and information for business growth. To carry out the Type 2 Diabetes market research study, professional and sophisticated methods and techniques such as SWOT analysis, and GRG Health’s unique GrowthMIX strategy were used.

The report is beneficial in providing information regarding several important questions that are vital for the market players such as manufacturers and partners, end users, etc. while assisting them in planning investments and capitalizing on market potential.

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What Next After Metformin? Guidelines and Indian Context

Authored by H B Chandalia

Go toPrevalence of T2DM in IndiaUnique challenges in managing T2DM in IndiaPathophysiological challenges of Indian T2DM patientsDietary differences in India and western countriesMetformin monotherapy- first line drugLimitations of current OADsSulfonylureas (SUs)Thiazolidinediones (TZDs)Incretin based therapiesInsulin therapySodium-glucose co-transporter 2 (SGLT2) inhibitors: novel therapy independent of InsulinDapagliflozinGlycemic efficacyNon-glycemic benefits of dapagliflozinWeight lossBlood pressureSafety profile of dapagliflozin

SGLT 2 inhibitors added on to metforminInternational guidelines for T2DMGo toStudy design

Abstract

There is a rapidly increasing epidemic of type 2 diabetes in India and other Asian countries due to rapid urbanization and lifestyle changes occurring in the country. India faces several challenges in diabetes management, including a rising prevalence in urban and rural areas, lack of disease awareness among the public, limited health care facilities, high cost of treatment, and rising prevalence of diabetic complications. Current antidiabetic agents fail to address disease progression and are often associated with weight gain and risk of hypoglycemia. SGLT2 represents a novel target for the treatment of diabetes. The mechanism of SGLT2 inhibition is independent of circulating insulin levels or insulin sensitivity; therefore, these agents can be combined in type 2 diabetes with all other antidiabetic classes, including exogenous insulin. Dapagliflozin is the first in class SGLT2 inhibitor that is associated with substantial improvements in glycemic control, reduction in weight especially fat mass, modest reduction in blood pressure and low risk of hypoglycemia. Besides this, there are indications that dapagliflozin is capable of improving β cell function and reduction in albuminuria. Although the long-term efficacy and safety of SGLT2 inhibitors remain under study, the class represents a novel therapeutic approach in the treatment of type 2 diabetes.

Keywords: Dapagliflozin; Metformin; SGLT2 inhibitors; Type 2 diabetes mellitus

Introduction

The prevalence of Type 2 diabetes is rising globally. A recent report by International Diabetes Federation (IDF) on the global scenario shows that the prevalence of diabetes in 2014 was 382 million and estimated to increase to an alarming 592 million by 2035.Nearly 80% of the diabetic population lives in the developing countries [1] and greater than 60% of world diabetes population will be in Asia [2]. Diabetes is fast gaining the status of a potential epidemic in India with more than 62 million diabetic individuals currently diagnosed with the disease [1]. It is predicted that by 2030 diabetes mellitus may afflict up to 79.4 million individuals in India, while China (42.3 million) and United States (30.3 million) will also see significant increases in the disease [1].

The etiology of diabetes in India is multifactorial and includes genetic factors along with environmental influences. Some of the major factors which pose unique challenges in managing T2DM in India are presented in Table 1. The prevalence estimates are escalating both in the urban and rural regions of India. Although the prevalence of diabetes is lower in low socioeconomic group versus the high-income groups living in urban areas, the former group has higher prevalence of complications. This is because they tend to neglect the disease due to lack of awareness and also due to economic barriers [3]. Low disease awareness among the population is also one of the major causes for diabetes epidemic [3]. Cost of diabetes care is very high and it increases many-fold in case of complications which require admission to hospital, surgery or insulin treatment. Many patients suffer from vascular complications at the time of diagnosis due to the fact that the person is asymptomatic and has low awareness about the disease. Early diagnosis of diabetes (at pre-diabetes stage) will make early initiation of treatment possible and thus avoid occurrence of vascular complications. Early intervention could also help to preserve the beta cell function [4]. Because of progressive nature of diabetes, patients fail to achieve target with multiple anti-diabetic agents. With early diagnosis and proper management, it may be possible to prevent T2DM along with its long term complications. Impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) representation pre-diabetic state which is also highly prevalent in India. Current estimates show that India has nearly 3.0% of adults with prediabetes [4].

The pathophysiology of T2DM is progressive, characterized by decreased insulin sensitivity, deteriorating beta cell function [5], and decreased incretin function [6]. Decreased insulin function leads to chronic hyperglycemia (during fasting and postprandial periods) and acute glycemic fluctuations. These may be associated with microvascular and macrovascular complications caused by excessive protein glycation and activation of oxidative stress [7-9].

As compared to western countries, India has a higher prevalence of diabetes despite having lower overweight and obesity rates, suggesting that diabetes may occur at a much lower body mass index (BMI) in Indians compared with Europeans [10]. Therefore, lean Indian adults with a lower BMI may be at equal risk as those who are obese [11]. Further, South Asian population has several unique characteristics like onset of diabetes at young age, a relatively lower BMI at the time of diagnosis with accompanying insulin resistance and reduced insulin secretory capacity. This body type is termed as thin-fat phenotype (thin muscle but increased body fat) and is associated with an increased risk of developing diabetes [10]. Indians develop T2DM at a younger age than the western populations and also develop diabetes with minor weight gain [12]. The development of the disease at a young age predisposes the patients to develop chronic long-term complications at a relatively young age with severe morbidity and early mortality in the most productive years of life [12]. Further, Indians are genetically predisposed to the development of coronary artery disease due to dyslipidaemia and low levels of high density lipoproteins; these determinants make Indians more prone to development of the complications of diabetes. Due to high ethnic and genetic susceptibility for the disease, Indians have lower threshold limits for the environmental risk factors and indicate that diabetes must be carefully screened and monitored regardless of patient’s age in India [13,14]. Under-nutrition during intrauterine development causes permanent changes in the structure and function of the developing systems of the fetus. This increases susceptibility to disease in later life. Asians mothers (especially in rural India) thought to be chronically undernourished because of their low BMI with iron and other nutrient deficiencies. One-third of Indian babies are born with low birth weight (LBW<2.5kg) [15]. It is thus possible that maternal and fetal under nutrition contribute to the diabetes epidemic in the Asian countries [15].

Studies have shown that in all parts of India, T2DM patients consume high total and complex carbohydrate (CHO) in their diet when compared with dietary recommendations. An earlier study has shown that 64.1±8.3% (95% CI 63.27 to 64.93) of total calories come from CHO in the T2DM group which has a direct effect on postprandial blood glucose and insulin response [16]. This suggests that CHO consumption by T2DM patients in India is higher than that recommended by the guidelines [16]. This unique feature in Indian dietary habit makes Indians more prone to T2DM as compared to western countries.

Metformin stands out not only for its antihyperglycemic properties but also for its effects beyond glycemic control such as improvements in endothelial dysfunction, oxidative stress, insulin resistance, lipid profiles and fat redistribution [17]. Negligible risk of hypoglycaemia when used in monotherapy and few drug interactions of clinical relevance give this drug a high safety profile and most preferred choice as first line therapy.

Current guidelines from ADA/EASD and AACE/ACE recommend early initiation of metformin as a first-line drug for monotherapy and combination therapy for patients with T2DM. This recommendation is based primarily on metformin’s glucose-lowering effects, relatively low cost, and generally low level of side effects, including the absence of weight gain [18]. The optimal second-line drug when metformin monotherapy fails is not clear.

T2DM is typically managed with rigorous medical therapy and a stepwise approach which includes lifestyle modifications, addition of oral antidiabetic drugs (OADs) and addition of insulin. OADs are normally introduced when lifestyle modifications fail to adequately controlglycemia. They are very useful for managing hyperglycemia, especially in the early stages of disease. Insulin and other antihyperglycemic agents like sulfonylureas (SUs), biguanides, thiazolidinediones (TZDs) and incretin based therapies are the drugs routinely used in the treatment of T2DM.However, there are several limitations that prevent antihyperglycemic agents from reaching their potential (Table 2).

SUs are as effective in lowering HbA1c, but their use is associated with hypoglycaemia and weight gain up to 2kg [17]. It has also been found that though they are effective in lowering the blood glucose rapidly in the initial phase of therapy, this effect is not sustained over time. SU therapy was implicated as a potential cause of increased cardiovascular disease mortality in the University Group Diabetes Program study [17].

TZDs, well known as insulin sensitizers, appear to have a more durable effect on glycemic control, particularly in comparison with SUs [19]. However, TZDs lead to weight gain, fluid retention, peripheral oedema, and a two-fold increased risk for congestive cardiac failure, potential for increased fracture risk [19].

Glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors offer analtered way of reducing hyperglycaemia by targeting the incretin system. GLP-1- based therapies have a beneficial effect on weight, because of their inhibitory effect on appetite via the gut-brain axis [20]. However, use of GLP-1 RA is associated with dose-dependent gastrointestinal side effects including nausea, vomiting and diarrhoea, and also two potential safety issues are pancreatitis and medullary carcinoma of the thyroid [21]. DPP 4 inhibitors are less potent to reduce hyperglycaemia compared to GLP 1 RA and besides that they are weight neutral [21].

Insulin therapy is often accompanied by hypoglycemia and weight gain which have been identified by patients and health care providers as common concerns prior to insulin initiation. These are key factors responsible for patients reluctance to insulin intensification [22]. Interestingly, the weight gain associated with insulin therapy is mainly seen in patients who had experienced significant weight loss prior to institution of insulin therapy [23]. Further, traditional vial and syringe method of insulin administration is associated with needle stick injury, social stigma, lack of convenience, difficulty with accurate dosing and therefore decreased adherence to the prescribed insulin regimen. New insulin analogs are effective in reducing HbA1c levels with a lower risk of overall and nocturnal hypoglycemia compared with conventional insulins [24]. They have also been shown to induce less weight gain than either NPH or insulin glargine [24].

Of immense therapeutic importance, intra subject coefficient of variation of insulin response has been shown to be 20-40%, 20% for human regular and rapid acting analogues and 40% for Neutral Protamine Hagedorn (NPH) and glargine insulin. All the above pharmacological drugs focus on reducing hyperglycemia and improving insulin sensitivity. These drugs target the primary defects associated with T2DM. However, despite the wide choice of treatment options available, glycemic control declines over time and eventually combination of other antihyperglycemic agents is required [25].

SGLT2 inhibitors are a new class of oral antidiabetic drugs, which reduce hyperglycemia by increasing urinary glucose excretion independent of insulin action [26]. SGLT2, located in the renal proximal tubule, reabsorbs90% of the filtered glucose [27] and its inhibition represents a new form of pharmacotherapy for the treatment of type 2 diabetes. The mechanism of action of SGLT2 inhibitors is unique and does not depend upon beta-cell function or tissue insulin sensitivity [26]. Through SGLT2 inhibition, reabsorption of tubular glucose is reduced and urinary glucose excretion increased [27] SGLT2 inhibitor induced glucose excretion is proportional to the amount of glucose filtered by the kidneys, which is a function of the glomerular filtration rate (GFR) and plasma glucose concentration [28]. Increased plasma glucose concentration (as observed in DM) leads to increased glucose filtration (dependent on the GFR) and may allow greater excretion of glucose with SGLT2 inhibition. The effect of SGLT2 inhibitors diminishes as patients plasma glucose concentrations decrease, the intrinsic risk of hypoglycemia with this drug class is low [28].

Dapagliflozin, a potent and selective SGLT2 inhibitor, has been shown to improve glycemic control in patients with type 2 diabetes when used as monotherapy [29-31] or in combination with metformin [32,33], sulfonylureas [34-36], thiazolidinedione [37], DPP4 inhibitors [38], or insulin [39].

Multiple trials have examined the efficacy of dapagliflozin versus placebo in lowering the HbA1c in drug-naive T2DM individuals. In a 24-week multicenter study [31], decrease in dapagliflozin treated subjects HbA1c was 0.5-0.6% (from a baseline HbA1c of 7.8-8.0%) and FPG decrease by ~25mg/dl (from a baseline FPG of 160mg/dl). In a subgroup of subjects with baseline HbA1c of 10.1-12.0%, dapagliflozin (5 and 10mg/ day) reduced the HbA1c by 2.88 and 2.66%, respectively. In another 24-week study [29,30], Dapagliflozin lowered the HbA1c by 0.7-0.8% from a baseline HbA1c of 7.8-8.1%. The efficacy of dapagliflozin in lowering the plasma glucose concentration as add-on therapy has been examined in poorly controlled T2DM treated with metformin, sulfonylureas and pioglitazone. Dapagliflozin effectively reduced the HbA1c in poorly controlled diabetic individuals independent of the background therapy. In a 24-week study [32], metformin-treated individuals with HbA1c 7-10% were randomized to receive different doses of dapagliflozin or placebo. The placebo-subtracted reduction in HbA1c at 24 weeks was -0.37 to -0.54%. Dapagliflozin also produced a dose-dependent decrease in FPG. 71% of subjects in this study participated in a 102-week extension study and the decrease in HbA1c was maintained at 102 weeks [33].

As add-on therapy, dapagliflozin has been shown to have similar potency to sulfonylureas in lowering the HbA1c in poorly controlled metformin-treated diabetic subjects. In a 52-week head-to-head study [34], meformin-treated subjects (HbA1c >6.5%) were randomized to receive dapagliflozin or glipizide. After an 8-week lead in period, dapagliflozin and glipizide were up-titrated over 18 weeks to 10 and 20 mg, respectively. The decrease in HbA1c at 52 weeks was identical in both groups (0.52%) [34], and the decrease in HbA1c in dapagliflozin-treated subjects was maintained at 102 weeks [35]. In a 24-week study [36], sulfonylurea treated subjects with poor glycemic control (HbA1c 7-10%) were randomized to receive different doses of dapagliflozin or placebo. The placebo-subtracted decrease in HbA1c was -0.44 to -0.68%, respectively. Dapagliflozin (5 and 10mg) has also been examined in a 24-week study [37] in poorly controlled (mean HbA1c 8.4%), pioglitazone-treated T2DM subjects. The placebo-subtracted decrease in HbA1c was -0.40 and -0.55%, respectively, and the decrease in HbA1c was maintained at 48 weeks. Dapagliflozin equally reduced the fasting and the postprandial plasma glucose concentration by ~ 25mg/dl.

In a larger study (n =800), [39] the addition of dapagliflozin (2.5, 5 and 10mg/day) to insulin-treated T2DM individuals (receiving ~70-80 units/day for a mean of ~6 years) caused a dose-dependent decrease in HbA1c (-0.40, -0.49 and -0.57%, respectively) compared with placebo over 24 weeks and the decrease in HbA1c was maintained at 48 weeks [39].

Other factors which play important role in the pathophysiology of T2DM were also improved by dapagliflozin alone or in combination with other diabetic drugs. Hypertension and albuminuria are risk factors for cardiovascular (CV) and renal disease in patients with T2DM [40]. Control of glycemia, blood pressure (BP) and albuminuria are critical for reducing CV and renal risk. Dapagliflozin reduces HbA1c and BP in patients with T2DM and also reduces urinaryalbumin:creatinine ratio in T2DM patients with hypertension using renninangiotensin system blockade without increasing any renal AEs [40]. Further, dapagliflozin improved glycemia in T2D patients with CVD, and improved insulin sensitivity in patients with T2D for up to 52 weeks. [41] Dapagliflozin alone and in combination with saxagliptin was shown to improve ßcell function and increased insulin clearance [42].

In addition to the beneficial effects related to improved glycemic control, dapagliflozin exerts additional non-glycemic benefits in T2DM patients that make the drug desirable as monotherapy and as combination therapy.

The urinary loss of 60-80g of glucose per day equates to a negative energy balance of 240 - 320 cal/day or an equivalent body weight of 2-3pounds/month if this caloric deficit is not offset by an increase in caloric intake. Consistent with this, weight loss was observed in diabetic subjects treated with dapagliflozin at all doses and at all stages of the disease [43]. Reduction in body weight was 2.26kg to 5.43kg as monotherapy [44], second add on therapy or add on to Insulin [44]. The weight loss primarily was due to a decrease in fat mass which is 2/3rd [44] while lean tissue mass reduction was 1/3rd as measured by dual-energy X-ray absorptiometry (DXA). Reduction in waist circumference was 2.5cm [44].

A consistent finding in all dapagliflozin studies has been a reduction in systolic/diastolic blood pressure of 4-5/2-3mmHg respectively [45]. This has been attributed to the diuretic effect that occurs during the initial days of dapagliflozin treatment [46]. Since uric acid and sodium reabsorption in the proximal tubule are coupled, decrease in serum uric acid concentration consistently has been observed in diabetic patients treated with dapagliflozin [47].

A major safety concern for anti-diabetic agents is the potential for patients to develop hypoglycaemia. Indeed, thus far, clinical trials have revealed virtually no instances of major hypoglycemic events, despite some increased risk of mild or moderate hypoglycemic events, which mostly occurred when they are superimposed with the background SU and Insulin therapy [34,39]. Clinical trials have consistently shown the early SGLT2 inhibitor dapagliflozin to be a safe agent for diabetic patients. Following an initial safety trial in healthy subjects showing that dapagliflozin was safe and well tolerated and did not induce hypoglycemia or produce any other adverse events [47], its safety was examined in type 2 diabetic patients, confirming that multiple oral doses of dapagliflozin rarely caused major hypoglycemia or other adverse events [29].

An increased incidence of mycotic vulvo-vaginal infections in women and mycotic balanitis in males has been observed. Rates of balanitis in men are several-fold less than rates of vulvovaginitis in women, and both infections are easily resolved by standard therapies [29]. SGLT2 inhibitors also possess a diuretic effect, hence symptoms related to volume depletion may occur [48]. Consequently, these agents should be used cautiously in elderly, any patient already on a diuretic, and patient with tenuous intravascular volume status.

Studies with dapagliflozin have demonstrated that treatment with an SGLT2 inhibitor has no deleterious effect on renal function [49]. Moreover, because the majority of drug’s clearance is by the liver, no dose adjustment is necessary in patients with renal impairment [49]. Because of its mechanism of action, the efficacy of dapagliflozin to reduce plasma glucose concentrations is highly dependent on the level of renal function. As the GFR declines, there is a decrease in the filtered glucose load and a progressive decrease in the glucose lowering ability of the drug. Thus dapagliflozin is not recommended if eGFR is <45 mi/min/1.73m2 [48].

It is possible that SGLT2 inhibitor therapy may prevent diabetic nephropathy. Enhanced sodium-glucose reabsorption in the proximal tubule has been shown to play an important role in the development of diabetic nephropathy [49]. SGLT2 inhibitors may prevent diabetic nephropathy not only by reducing the plasma glucose concentration but also by increasing sodium delivery to the distal nephron, thereby inhibiting the glomerulotubular feedback reflex [49]. Type 2 diabetes is a major risk factor for cardiovascular (CV) disease, and the presence of both Type 2 diabetes and cardiovascular disease increases the risk of death [50]. There is concern that intensive glucose lowering or the use of specific glucose-lowering drugs may be associated with adverse cardiovascular outcomes. Therefore, it is necessary to establish the cardiovascular safety benefits of glucose-lowering agents [51]. Since the mode of action of SGLT2 inhibitors is independent of insulin secretion; these agents are associated with a low risk of hypoglycemia, which has been linked to increased CV events. In addition, the drug has been demonstrated to ameliorate a variety of CV risk factors and potential pathways as described in Figure 1 [52]. Dapagliflozin has an acceptable CV profile. Meta-analyses have been performed analyzing the cardiovascular safety of dapagliflozin [53].

Meta-analysis did not show an increased CV risk for dapagliflozin-treated patients, with no evidence for an increased risk of major CV events and with hazard ratios <1 consistently across various composite CV endpoints and across different subgroups [53]. Also, EMPA-REG study with Empagliflozin, another SGLT2, showed that T2DM patients with high risk for cardiovascular events who received empagliflozin, as compared with placebo, had a lower rate of the primary composite cardiovascular outcome and of death from any cause when the study drug was added to standard care [54]. In CVD REAL, A large multinational study, treatment with SGLT-2i versus oGLDs was associated with a lower risk of HHF and death, suggesting that the benefits seen with empagliflozin in a randomized trial may be a class effect applicable to a broad population of T2D patients in real-world practice [55]. In CVD REAL Nordic study a total of 40,908 patients with T2D were identified as new users of dapagliflozin (n=10227) ora DPP 4 inhibitor (n=30681). Dapagliflozin was associated with a lower risk of MACE, HHF and all-cause mortality compared with DPP-4 inhibitors: HRs 0.79 (95%confi-dence interval [CI] 0.67-0.94), 0.62(95% CI 0.50- 0.77), and 0.59(95% CI 0.49-0.72), respectively [56].

Recently, the U.S. Food and Drug Administration (FDA) issued a Drug Safety Communication that warns of an increased risk of diabetic ketoacidosis (DKA) with surprisingly mild to moderate glucose elevations (euglycemic DKA [euDKA]) associated with the use of all the approved sodium-glucose cotransporter 2 (SGLT2) inhibitors [57]. In the randomized controlled T2D study program, more than 18,000 patients exposed to dapagliflozin and the frequency of reported events suggestive of DKA (blinded and unblinded events) was less than 0.1% [56]. Similarly in DECLARE study 17,150 patients randomized todapagliflozin or placebo, the total number of reported blinded events of potential DKAs is less than 0.1% [58]. In a retrospective analysis of randomized phase 2 and 3 empagliflozin trials (13,000 T2D participants), there were eight events consistent with DKA with no imbalance observed between patients treated with empagliflozin 10mg (two events), empagliflozin 25mg (one event), and placebo (five events) [59]. The canagliflozin (another SGLT2 inhibitor) data reported by Erondu et al. [60] appeared to have a greater incidence of DKA, but 6 out of the 12 cases had evidence of latent autoimmune diabetes in adults or T1D or tested positive for GAD65 antibodies. Thus the evidence so far suggests that the risk of euDKA (and not simple ketosis) in T2DM related to the use of SGLT2 inhibitors will probably turn out to be very low with an acceptable frequency. Still, physicians and patients need to be made aware that such risk may be increased in long-standing T2DM patients with marked beta-cell insufficiency or in latent autoimmune diabetes. This potential complication related to SGLT2 inhibition is predictable, detectable, and preventable so that the balance of benefits and risks favors the use of SGLT2 inhibitors in the T2DM population [58].

Numerous preclinical and clinical studies indicate that SGLT2 inhibitors are efficacious but still they may not be the first choice for T2DM therapy. Currently, the standard first line therapy is metformin, due to its low cost and favourable safety profile. SGLT2 inhibitors could quickly become a second-line therapy, and may possibly replace metformin as the first-line therapy in the future [61]. SGLT2 inhibitors may be a particularly good choice for T2DM patients who do not achieve adequate glycaemic control with metformin or other anti-diabetic drugs. In two clinical studies, dapagliflozin as an add-on to metformin decreased HbA1c levels significantly without any serious adverse effects [32].

ADA guidelines recommend weight loss for all overweight or obese individuals who have /are at risk for diabetes. Weight reduction is especially important in Asians who have lower cut-offs for overweight and obesity and hence are highly predisposed to development of diabetes and worsening of diabetes [59]. Shantha et al. [60], in 2012 demonstrated that intentional weight loss of 10% in obese individuals with T2DM could potentially decrease percentage HbA1c by 0.81%. WHO recommends lowered cut-off points for overweight/obesity for Asians in the Asia Pacific region (overweight: BMI =23 kg/m² in comparison with 25kg/m² for western populations) [10].

The major change in treatment options since the publication of the 2012 position statement has been the availability of a new class of glucose-lowering drugs, the sodium-glucose cotransporter 2 (SGLT2) inhibitors. These agents reduce HbA1c by 0.5-1.0% (5.5-11mmol/mol) versus placebo [61]. When compared with most standard anti-diabetic agents in headto- head trials, they appear to be roughly similarly efficacious with regard to initial HbA1c lowering [62]. Additional potential advantages include modest weight loss and consistent lowering of systolic and diastolic blood pressure along with reductions in plasma uric acid levels and albuminuria [63]. Current treatment guidelines approved SGLT2 inhibitors as monotherapy, they are mainly used in combination with metformin and/or other agents. Given their demonstrated efficacy and clinical experience to date, they are reasonable options as second-line or third-line agents [61].

All major organizations (American Diabetes Association (ADA)/European Association for the Study of Diabetes (EASD)/ American Association of Clinical Endocrinologists (AACE)) recommend metformin as first-line therapy in individuals with new-onset diabetes and also recommend as a combination therapy with other anti-diabetic agent in case of disease progression. Dapagliflozin is an effective novel strategy to reduce the plasma glucose concentration in type 2 diabetic subjects. The drug’s unique mechanism of action, which is independent of insulin sensitivity and beta cell function, allows the use of dapagliflozin in combination with all other antidiabetic agents and at all stages of the disease. However, because metformin does not improve beta cell function, metformin-treated individuals experience a progressive increase in HbA1c after the first year of therapy. Dapagliflozin can provide an effective therapeutic option in metformin-failing diabetic individuals. An increase in the plasma glucagon-like peptide-1 (GLP-1) concentration has been observed in some clinical studies following initiation of dapagliflozin therapy. This observation makes the double combination of dapagliflozin plus a dipeptidyl peptidase IV (DPP-IV) inhibitor an attractive therapeutic option in metformin-failing individuals. In newly diagnosed T2DM individuals with a very high HbA1c (e.g., >9.0%), metformin alone will not lower the HbA1c to the treatment goal (<7.0%). Dapagliflozin plus metformin have an additive effect to lower the HbA1c. Dapagliflozin monotherapy produces a profound decrease in HbA1c in patients with a high initial HbA1c (>9.0%). The combination of dapagliflozin plus metformin is an attractive therapeutic option in newly diagnosed diabetic individuals with a high initial HbA1c. Dapagliflozin can provide an effective therapeutic option in metformin-failing diabetic individuals. Metformin cannot be started in about 10- 20% of subjects with new-onset diabetes due to either gastrointestinal (GI) side effects or due to renal failure. Thus, dapagliflozin, as monotherapy or in combination with a DPP-IV inhibitor, can provide an effective initial therapy in metformin-intolerant individuals. Because dapagliflozin is effective in lowering the HbA1c at all stages of diabetes, it can be added in subjects who fail on multiple oral agent therapy or in insulin-treated individuals who do not reach the target glycemic control. Progressive beta-cell failure is the principle factor responsible for the progression of T2DM. Thus, preservation of β-cell function can be expected to produce a durable reduction in HbA1c. More data will be required before making definitive conclusions about the durability of dapagliflozin. To the extent that glucotoxicity contributes to the decline in beta-cell function in subjects with impaired glucose tolerance (IGT) or impaired fasting glucose (IFG), these drugs also may prove useful in the treatment of ‘prediabetes’. Lastly, unlike most currently available antidiabetic agents, SGLT 2 inhibitors promote weight loss and reduces blood pressure which would be expected to have potential cardiovascular benefit [64,65].

Conclusion

The pathogenesis of type 2 diabetes involves numerous defects and no single anti-diabetic agent can correct all these metabolic disturbances. An effective anti-diabetic therapy will require multiple drugs used in combination. Based on expert commentsinhibition of SGLT2 represents a highly promising therapeutic approach for T2DM treatment. With a unique mechanism of action-increased urinary glucose excretionthe SGLT2 inhibitors can be used as monotherapy as well as in combination with currently available anti-diabetic agents. Their distinct, targeted mechanism of action makes SGLT2 inhibitors good candidates for combination therapies with other anti-diabetic agents as well as insulin. Moreover, due to their high potential to control hyperglycemia, effect on visceral fat and improvement in insulin sensitivity, SGLT2 inhibitors are expected to have protective effects against micro and macrovascular complications. With these properties, the SGLT2 inhibitors have potential for use throughout the continuum of diabetes treatment in Indian populationas Indian patient’s needs are unique due to environmental, social and genetic facts. Considering International glycemic control guidelines, mechanism of action, substantial improvements with respect to glycemic and extragycemic parameters and safety profile associated with Dapagliflozin, it could be excellent choice for managing T2DM after metformin in Indian patients.

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Prospect of Marine Bioactive Peptides as DPP4 Inhibitor

Authored by:  Md Morshedul Alam

Abstract

Dipeptidy peptidase 4 (DPP4) is an enzyme that plays important role in metabolism and due to its exacerbating role in glucose metabolism, it is essential to inhibit its function to ameliorate Type 2 Diabetes Mellitus (T2DM). Vildagliptin, sitagliptin and some other drugs are being used worldwide. As a new source, marine derived bioactive peptide having DPP4 inhibitory effect would have a promising role to control its regulatory effect on disease manifestation.

Keywords: DPP4 inhibition; Marine derived origin; Marine bioactive peptide

Abbreviations: DPP4: Dipeptidy Peptidase 4; T2DM: Type 2 Diabetes Mellitus; GIP: Glucose-Dependent Insulinotropic Polypeptide; GLP1: Glucagon-like Peptide-1; ROS: Reactive Oxygen Species, RAGE: Receptor for Advanced Glycation End Products; FDA: Food and Drug Administration; APCs: Antigen-Presenting Cells

    Introduction

Dipeptidyl peptidase 4 (DPP4)/CD26 is a serine exopeptidase enzyme that cleaves the N-terminal dipeptides with proline or alanine amino acids from the N-termini of polypeptides leading to regulate the activities of a number of peptide hormones and chemokines. It is known that DPP4 is responsible for the degradation of several incretins such as glucagon-like peptide-1 (GLP1), glucose-dependent insulinotropic polypeptide (GIP), thus regulating the blood glucose level by sensitizing insulin secretion [1]. Upon T cell stimulation, DPP4 expression is markedly up-regulated along with its increased release in soluble form in the blood, which also suggests DPP4 as a T cell co-stimulatory molecule that exerts its effect through binding to adenosine deaminase and interacting with T cell receptor complex. Bunch of studies suggests that DPP4 is a novel adipokine, which is correlated with the amount of adipose tissue inflammation, and insulin resistance as well. Several reports suggest that DPP4 is also released in soluble form exerts lots of cellular effects such as stimulation of reactive oxygen species (ROS), induction of inflammation in smooth muscle cells. Generally, soluble DPP4 interacts to cell surface receptor(s) and executes numerous effects such as activation of T cells, induction of smooth muscle cells inflammation, stimulation of insulin resistance in various tissues, augmentation of CD86 in antigen-presenting cells (APCs), enhancement of smooth muscle cell proliferation, stimulation of reactive oxygen species (ROS) generation and induction of receptor for advanced glycation end products (RAGE) gene expression, and so on [2].

To manage the excessive adverse effects of DPP4 at the cellular level, scientists are suggesting some pharmacological intervention as a drug and in this case vildagliptin, sitagliptin, approved by the Food and Drug Administration (FDA), are most widely used. Beside these two drugs, saxagliptin and alongliptin are also being suggested [3]. Most of the cases these drugs are approved to be used in a combinatorial therapy like in combination with metformin, sulphonylureas, thiazolidinediones etc. As an alternative source of DPP4 inhibitor, marine derived sources would have a great potential in therapy [4] and more specifically marine derived bioactive peptides production would be one of the areas of utmost interest in DPP4 inhibitor activity. It is known that ficin digested gliadins-derived peptides possess strong dipeptidyl peptidase 4 inhibitory activity as well as antihypertensive and antioxidant activities. As a functional food or dietary supplement, marine peptides derived from seaweeds, sponges, fish-skin, fish-bones, fish-scales, mollusks, crustaceans and marine byproducts including substandard muscles, viscera and trimmings would have a great potential targeting DPP4 inhibition. It is known that Gly-Pro-Ala peptide works as a DPP4 inhibitor, which has a great relevance as a natural source for Type II diabetes mellitus (T2DM) management in both in vitro and in vivo through incretin effect. In one study using RubisCO of Halophila stipulacea, a sea grass, lots of bioactive peptides were found by using chymotripsine digestion, which showed strong DPP4 inhibitory activities such as GL, PL, GF, KY, RL, TY, VF. In the same species, trypsine digestion gives DPP4 inhibitory activity with the bioactive peptide sequence of DF. Proteinase K digestion also gives DPP4 inhibitory function with TP, SP, KP, EP, QP, AY, EY, GV, HI, QV, RI, TP and so on. In line with these, pancreatic elastase digestion provides several important bioactive peptide sequences having DPP4 inhibitory role such as RA, PL, WT, ET, KG, KT, NV, RG, and so on [5]. Thus, marine source as a bioactive peptide would have huge potential.

The recent age, blue economy emerged a lot of potential and various countries are now focusing on exploring the marine resources in their coastal region. Various pharmaceutical companies are also searching for new sources of secondary metabolites and as a DPP4 inhibitory agent, bioactive peptide from marine origin would open a new window to explore this field.

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