Overview of Diabetes Treatment

Insulin and Insulin Analogs

Insulin is vital for managing diabetes, particularly in type 1 and advanced type 2 patients. Traditional insulin and analogs like glargine, lispro, and aspart improve patient outcomes by closely mimicking physiological insulin profiles, activating insulin receptors to enhance glucose uptake and regulate blood glucose levels.

Related Services at Ace Therapeutics

• Preclinical Development of Insulin Analogs
• PK/PD Studies of Insulin and Insulin Analogs
• In Vivo Efficacy Models
• Bioanalytical Assays

Oral Hypoglycemic Agents (OHAs)

Metformin - As a widely used first-line treatment, metformin primarily works by reducing hepatic glucose production and enhancing insulin sensitivity. This dual action helps lower blood sugar levels effectively.

Sulfonylureas and Meglitinides - These medications stimulate pancreatic beta cells and promote the secretion of insulin. Increased insulin levels help lower the level of blood glucose.

DPP-4 Inhibitors - DPP-4 inhibitors are a class of oral hypoglycemic drugs that inhibit the enzyme dipeptidyl peptidase-4 (DPP-4). DPP-4 inhibitors enhance incretin hormone activity, which aids insulin secretion and reduces glucagon release.

Related Services at Ace Therapeutics

• Preclinical Development of Oral Hypoglycemic Agents
• Efficacy Studies of Oral Hypoglycemic Agents
• Combinatorial Drug Testing
• Metabolic Assessments
• Diabetic Animal Models
• Enzymatic Assays (e.g., DPP-4 Activity)

GLP-1 Receptor Agonists

Liraglutide and semaglutide, amongst others, have emerged as one of the most reviewed GLP-1 receptor agonists in both diabetes management and the treatment of obesity. These drugs act by mimicking the action of a naturally occurring hormone, GLP-1, which is secreted in response to nutrient intake. They thus bind to GLP-1 receptors, stimulating insulin secretion in a glucose-dependent manner and hence lower blood glucose.

Related Services at Ace Therapeutics

• GLP-1 New Drug R&D Service
• Chronic Efficacy Studies for Glycemic Control and Weight Management
• Pharmacokinetic Profiling
• In Vivo Safety Assessments
• Mechanistic Studies on GLP-1 Pathway Activation
• Combination Therapy Assessments

Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

These drugs include empagliflozin and canagliflozin, which are classified under a class of SGLT2 inhibitors. The mechanism of their action involves inhibiting the protein SGLT2 in the kidneys to reduce blood glucose levels. This inhibition reduced glucose reabsorption from the renal tubules and enhanced its excretion through the urine at higher rates.

Related Services at Ace Therapeutics

• SGLT2 New Drug R&D Service
• Efficacy in Diabetic Nephropathy Models
• Pharmacodynamic Monitoring
• Long-Term Safety Evaluations
• Comparative Effectiveness Research

Thiazolidinediones (TZDs)

Thiazolidinediones (such as pioglitazone and rosiglitazone) primarily lower blood glucose by enhancing insulin sensitivity in adipose tissue, muscle, and liver.

Related Services at Ace Therapeutics

• Preclinical Development of TZDs
• In Vivo Efficacy Studies: Assess TZDs' effects on glucose regulation in various animal models.
• Mechanistic Studies: Investigate the impact of TZDs on insulin signaling pathways and adipocyte function.
• Long-Term Toxicology Assessments: Monitor potential long-term effects on cardiovascular and liver health.

Alpha-Glucosidase Inhibitors

Acarbose and miglitol, along with other alpha-glucosidase inhibitors, can reduce post-meal blood sugar levels by stopping the absorption of carbohydrates in the intestine.

Related Services at Ace Therapeutics

• Preclinical Development of Alpha-Glucosidase Inhibitors
• Efficacy Testing for Alpha-Glucosidase Inhibitory Activity
• Digestive Enzyme Assays
• Combination Therapy Studies

Glucagon Receptor Antagonists

Glucagon receptor antagonists (such as monoclonal antibodies or small molecules targeting glucagon) aim to lower blood glucose levels by reducing hepatic glucose production and indirectly promoting insulin secretion through improved glucose homeostasis.

Related Services at Ace Therapeutics

• Preclinical Development of Glucagon Receptor Antagonists
• Mechanistic Evaluations: Study the effects of glucagon receptor antagonists on liver metabolism.
• Pharmacokinetic Studies: Analyze the pharmacokinetics of different administration routes.
• Safety Assessments: Evaluate long-term safety effects on the cardiovascular system and other organs.

Bile Acid Sequestrants

Medications like colesevelam are bile acid sequestrants that reduce the level of blood sugar by binding to bile acids, which inhibit their reabsorption. This in turn improves cholesterol levels.

Related Services at Ace Therapeutics

• Preclinical Development of Bile Acid Sequestrants
• Preclinical Animal Studies: Efficacy and safety studies related to bile acid sequestrants, including their effects on glucose levels.
• Cholesterol Profiling: Changes in cholesterol and lipid profile should be monitored to see its impact on the incidence of cardiovascular disease.
• Metabolic Pathway Analysis: investigate the influence of the drug on various metabolic pathways in the liver and intestines.

Closed-Loop Systems and Artificial Pancreas

Emerging closed-loop systems and artificial pancreas technologies are at the core of the revolution in diabetes management, thus enabling a far more automatic and responsive insulin therapy compared to what has ever been possible. These systems integrate continuous glucose monitoring with automated insulin delivery through seamless feedback mechanisms that almost perfectly mimic the function of a healthy pancreas.

Fig 1. Closed loop artificial pancreas. (Dler Saber, et al., 2013)

Gut Microbiota and Metabolic Health

Gut microbiota has emerged as a very indispensable field in research with regard to the role it plays in glucose metabolism, regulation of insulin sensitivity, and generally in metabolic health. Evidence is emerging to show that gut microbiota variation and diversity can importantly cause changes in metabolic disorders such as type 2 diabetes.

Fig 2. Gut microbes are linked with metabolic disorder. (Cani PD, et al., 2021)

Anti-inflammatory Approaches

Chronic inflammation is considered a critical contributor to the pathogenesis and development of diabetes, partly through the regulation of insulin resistance and metabolic changes. Thus, targeting inflammation with pharmacological interventions provides a promising approach for the management of metabolic health and treatment of diabetes.

Fig 3. A schematic presentation of the concept of metaflammation. (Kuryłowicz A, et al., 2020)

Gene Editing Technologies

Innovations in gene editing technologies, including CRISPR-Cas9, could offer potential to correct genetic defects driving diabetes.

Biologics and Novel Drug Formulations

Biologics, especially monoclonal antibodies and fusion proteins, are emerging as targeted therapies for diabetes. In addition, the development of novel drug formulations, such as liposomes, nanoparticles, depot formulations, and inhalable biologics, is playing a key role in improving the delivery, stability, and effectiveness of these biologic therapies.