Treatment of Type 2 Diabetes Mellitus: Modern Drugs and Approaches

Type 2 diabetes mellitus (T2DM) has turned into a global pandemic affecting millions of people worldwide. According to WHO projections, by 2030, diabetes will rank as the seventh leading cause of death [2]. This disease not only significantly impairs quality of life but also carries a high risk of developing severe complications, such as atherosclerotic cardiovascular events and heart failure (HF) [1]. Modern approaches to treating T2DM go far beyond simple glucose control, focusing on comprehensive organ protection and improving long-term patient outcomes.

Evolution of Treatment Approaches: From Glycemia to Organ Protection

For a long time, outpatient diabetes care was primarily focused on preventing microvascular complications and maintaining target glycemic levels [3]. However, recent studies have shown that patients with T2DM have a 2-to-4-fold increased risk of developing heart failure, as well as a high risk of cardiovascular mortality [1, 3]. This has led to a rethinking of treatment strategies and the need for closer collaboration between cardiologists and diabetologists to optimize cardiovascular prevention and heart failure management [1].

Despite the availability of numerous approved drugs for T2DM, many patients fail to achieve adequate glycemic control due to various factors [2]. Therefore, the search for new therapeutic options with multiple actions and better efficacy remains relevant. The WHO also emphasizes the importance of adhering to clinical guidelines for glycemic control for more effective diabetes management [2].

Innovative Drug Classes: SGLT2i and GLP-1 RA

Recent years have been marked by the emergence of new drug classes that not only effectively lower glucose levels but also demonstrate significant benefits in cardiovascular and renal protection.

Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i)

This class of drugs has revolutionized the treatment of T2DM. SGLT2i block glucose reabsorption in the kidneys, promoting its excretion in the urine and thereby lowering blood sugar levels. However, their key advantage lies in their pronounced cardio- and nephroprotective effects [1]. Numerous randomized clinical trials and meta-analyses have provided compelling evidence of the benefits of SGLT2i, particularly in the treatment of heart failure, both in patients with and without diabetes [1]. Studies such as DAPA-HF have shown unexpected and remarkable results confirming their efficacy in the prevention and treatment of HF [1].

Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA)

GLP-1 RA stimulate insulin secretion in a glucose-dependent manner, suppress glucagon secretion, delay gastric emptying, and promote a feeling of fullness, leading to weight loss. They have also shown strong evidence of benefit in cardiovascular prevention [1]. Since 2005, several GLP-1 RA have been approved, including liraglutide, albiglutide, dulaglutide, lixisenatide, as well as weekly formulations of exenatide and semaglutide [7]. The mechanisms of action of GLP-1 RA, as well as dual GIP/GLP-1 receptor agonists, share similarities with endocrine changes following bariatric surgery, making it possible to consider them as a means to achieve pharmacological remission of diabetes [4].

Other Modern Therapeutic Strategies

In addition to SGLT2i and GLP-1 RA, there are other important areas in the treatment of T2DM:

• Lipid-lowering therapy: For patients with T2DM who are at high cardiovascular risk, lipid-lowering drugs such as PCSK9 inhibitors and icosapent ethyl play an important role [1].
• Bariatric surgery: For patients with T2DM and obesity, bariatric surgery is considered one of the most effective and long-term treatments. Many patients achieve normalization of glucose levels within a few days after surgery [5].
• Intensive weight loss programs: Losing more than 10-15 kg as part of intensive programs can lead to T2DM remission, when glucose and HbA1c levels drop below the diagnostic threshold [4].
• Pharmacological remission: It has been proposed to consider a separate category of diabetes remission achieved and maintained with highly effective glucose- and weight-lowering medications. This may be relevant because modern drugs allow patients to safely achieve HbA1c and glucose levels below current thresholds for defining remission [4].

Comprehensive Approach and Treatment Personalization

Lifestyle modification, including diet and physical activity, remains the cornerstone of T2DM treatment, especially in obese patients, and is highly effective in promoting glucose regulation [5]. However, many people eventually experience difficulties maintaining optimal glycemic control and/or body weight through lifestyle changes alone. Therefore, additional therapeutic approaches are needed [5].

Obesity treatment in patients with T2DM requires a multifaceted approach [5]. Despite the abundance of FDA-approved therapeutic options, a significant portion of patients fail to achieve adequate glycemic control [2]. In China, for example, the most common oral antidiabetic drugs are insulin secretagogues (sulfonylureas, glinides), metformin, and alpha-glucosidase inhibitors. At the same time, two-drug combination therapy is more common (45.4%) than monotherapy (35.8%) [8].

Future research is also focused on finding common therapeutic strategies for T2DM and other conditions, such as Alzheimer's disease, given their epidemiological and pathological relationship, for example, through enzyme targeting [6].

Conclusion

Modern treatment of type 2 diabetes mellitus has undergone significant changes, shifting the focus from purely glycemic control to comprehensive cardiovascular and renal protection. Innovative drugs such as SGLT2i and GLP-1 RA, combined with traditional methods, lifestyle changes, and, if necessary, bariatric surgery, offer new opportunities to improve patient prognosis and quality of life. A personalized and multifaceted approach, as well as close cooperation between specialists, are the key to effectively managing this complex disease.

Sources

• [1] The interplay between cardiology and diabetology: a renewed collaboration to optimize cardiovascular prevention and heart failure management. https://pubmed.ncbi.nlm.nih.gov/32402065/
• [2] Treatment Avenues for Type 2 Diabetes and Current Perspectives on Adipokines. https://pubmed.ncbi.nlm.nih.gov/28081698/
• [3] Heart failure management; a perspective from diabetes care. https://pubmed.ncbi.nlm.nih.gov/33957144/
• [4] Challenging the Consensus Statement: Is It Time to Recognise Pharmacological Remission of Type 2 Diabetes? https://pubmed.ncbi.nlm.nih.gov/41852334/
• [5] Type 2 Diabetes Treatment in the Patient with Obesity. https://pubmed.ncbi.nlm.nih.gov/27519130/
• [6] Alzheimer's and type 2 diabetes treatment via common enzyme targeting. https://pubmed.ncbi.nlm.nih.gov/24059315/
• [7] Addressing Unmet Needs With Injectable Medications in Type 2 Diabetes Treatment: Glucagon-Like Peptide-1 Receptor Agonists. https://pubmed.ncbi.nlm.nih.gov/28991932/
• [8] China type 2 diabetes treatment status survey of treatment pattern of oral drugs users. https://pubmed.ncbi.nlm.nih.gov/24809622/

The information provided in this article is for reference purposes only and does not replace professional medical advice. Always consult a physician or other qualified healthcare professional with any questions regarding your health or treatment.