Modern therapy in type 2 diabetes mellitus – what should you know?

Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Chronic hyperglycemia is associated with long-term damage, dysfunction, and failure of various organs, especially the eyes, kidneys, nervous system, heart, and blood vessels. (1)

Long-term complications include retinopathy with potential vision loss; nephropathy leading to renal failure; peripheral neuropathy with risk of foot ulcers, amputation, and Charcot arthropathy; and autonomic neuropathy causing gastrointestinal, genitourinary, cardiovascular symptoms and sexual dysfunction. (1)

Type 2 diabetes mellitus develops due to progressive loss of adequate β-cell insulin secretion in the presence of peripheral insulin resistance. (1)

Oral antihyperglycemic therapy consists of several groups depending on their mechanism of action: (3,4)

1. Biguanides (metformin)

2. Sulfonylureas (glipizide, glyburide, gliclazide, glimepiride)

3. Thiazolidinediones (pioglitazone, rosiglitazone)

4. Glinides (repaglinide, nateglinide)

5. Alpha-glucosidase inhibitors (acarbose, miglitol, voglibose)

6. DPP-4 inhibitors (sitagliptin, saxagliptin, vildagliptin, linagliptin, alogliptin)

7. SGLT2 inhibitors (dapagliflozin, canagliflozin)

Mechanism of action

1. Biguanides – usually first-line therapy. They inhibit hepatic glucose production. Metformin improves insulin sensitivity and is prescribed at diagnosis when insulin resistance is present and endogenous insulin reserves are sufficient.

2. Sulfonylureas – insulin secretagogues that stimulate endogenous insulin secretion. Representatives include gliclazide, glimepiride, glibenclamide, and glipizide.

3. Thiazolidinediones – insulin sensitizers acting via activation of PPAR-γ, increasing insulin sensitivity, peripheral glucose uptake, adiponectin levels, and fatty acid oxidation.

4. Glinides

Repaglinide – short-acting agent that lowers blood glucose by stimulating pancreatic insulin release.
Nateglinide – activity depends on functional beta cells. They do not stimulate insulin release in absence of glucose and have minimal effect between meals. Vascular effects are not sufficiently studied. (5)

5. Alpha-glucosidase inhibitors – reduce carbohydrate absorption in the small intestine and decrease postprandial glucose rise.

6. DPP-4 inhibitors – prolong the action of GLP-1 and enhance glucose-dependent insulin secretion.

7. SGLT2 inhibitors – reduce renal glucose reabsorption and increase urinary glucose excretion. They have demonstrated cardiovascular safety and benefit.

Oral therapy must be used cautiously in patients with renal or hepatic impairment, with dose adjustment or discontinuation in acute failure.

Combination of oral antidiabetic drugs

Table 1- adapted from reference number. 5

References:

1. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus

The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.Diabetes Care. 2000;23(1s), достапно на: https://www.medscape.com/viewarticle/412642_2?form=fpf, последно пристапено на: 22.01.2024

2. Davies, M.J., Aroda, V.R., Collins, B.S. et al.Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia65, 1925–1966 (2022). Достапно на: https://doi.org/10.1007/s00125-022-05787-2, последно пристапено на 01.11.2023
3. Ganesan K, Rana MBM, Sultan S. Oral Hypoglycemic Medications. [Updated 2023 May 1]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov /books/NBK482386/ Последно пристапено на 01.11.2023.