Classification of drugs in diabetes mellitus
All agents used in diabetology can be divided into two groups with opposite effects. The main pool consists of hypoglycemic agents, which lower blood sugar levels. These include:
- Insulin preparations. This is basic replacement therapy, which is life-saving in type 1 diabetes, but can also be prescribed in type 2.
- Synthetic oral agents. An extensive group of drugs classified by their site of action and effect on hormone secretion (sulfonylureas, biguanides, DPP-4 inhibitors, SGLT2 inhibitors, and others).
The second group consists of hyperglycemic agents (antagonists). A prominent representative is glucagon preparations. Unlike other drugs, they increase glucose concentration and are used exclusively for emergency management of severe hypoglycemia.
Mechanism of action of insulin
Insulin exerts its effects not directly, but by binding to specific receptors on the cell surface. This triggers a complex cascade of intracellular reactions leading to two main results:
- Enhanced glucose transport. In insulin-dependent tissues (which include muscle and adipose tissue), translocation of specific GLUT-4 transporters occurs. They move from the cytoplasm to the cell membrane and actively uptake sugar from the blood.
- Changes in intracellular metabolism. The hormone activates glycolysis enzymes, accelerating glucose utilization for energy production. Simultaneously, glycogen synthase—the enzyme responsible for glycogen synthesis—is stimulated, thanks to which glucose is stored in the liver and skeletal muscles.
It is important to note that insulin does not affect carbohydrate absorption in the intestine and does not enhance renal sugar excretion (these mechanisms are characteristic of other drug groups).
Endogenous insulin secretagogues
In type 2 diabetes mellitus, oral medications are often used to force the pancreatic beta cells to produce more of their own insulin. Such secretagogues include:
- Sulfonylureas (e.g., glibenclamide).
- Meglitinides (glinides). A typical representative is nateglinide, a phenylalanine derivative. It selectively blocks ATP-dependent potassium channels of beta cells. The drug enhances the earliest phase of secretion in response to glucose, provides a short insulin response, and is well suited for the prevention of postprandial hyperglycemia (blood sugar spikes after eating).
- Incretin mimetics and enhancers. These include glucagon-like peptide-1 (GLP-1) receptor agonists, which stimulate glucose-dependent secretion, as well as dipeptidyl peptidase-4 (DPP-4) inhibitors known as gliptins (e.g., saxagliptin).
Drugs with extrapancreatic action
Certain oral agents do not force the pancreas to work to exhaustion, but act on other links of metabolism:
- Biguanides. The main representative of this group is metformin. Unlike sulfonylureas, it does not stimulate insulin production at all. Its task is to reduce insulin resistance, that is, to increase the sensitivity of peripheral tissues to the already existing hormone.
- Alpha-glucosidase inhibitors. A representative of the group is acarbose, which is chemically a tetrasaccharide. The drug works exclusively in the lumen of the small intestine and is practically not absorbed into the systemic circulation. It competitively blocks the enzyme alpha-glucosidase, thereby slowing down and reducing the absorption of glucose from complex dietary carbohydrates. The main disadvantage of this mechanism is dyspeptic disorders (diarrhea, flatulence) arising from the fermentation of unabsorbed carbohydrates by the intestinal microflora.
Briefly: answers to topical questions
What specific drugs belong to the sulfonylurea group?
The sulfonylurea group includes the following specific drugs:
- Glibenclamide (including micronized).
- Gliclazide (including modified release gliclazide).
- Glimepiride.
- Gliquidone.
Sulfonylureas stimulate insulin secretion. For this group, rapid achievement of the glucose-lowering effect and low cost are indicated, along with disadvantages such as the risk of hypoglycemia, rapid development of resistance, and weight gain.
What is the mechanism of action of SGLT2 inhibitors (flozins)?
The mechanism of action of SGLT2 inhibitors (flozins) consists in blocking the sodium-glucose cotransporter 2 in the proximal renal tubules. This leads to a decrease in glucose and sodium reabsorption, returning them to the primary urine. As a result, sodium and glucose remain in the urine and draw water along with them, causing diuresis and natriuresis. This mechanism is insulin-independent and additionally contributes to weight loss. The effect of the drugs is mild, constant, does not cause acute dehydration, and does not activate the renin-angiotensin-aldosterone system.
What insulin preparations are distinguished depending on their duration of action?
Depending on the duration of action, the following groups of insulin preparations are distinguished:
- Ultra-short-acting insulins — insulin analogs: insulin lispro, insulin aspart, insulin glulisine.
- Short-acting insulins — e.g., Actrapid HM; neutral insulin for injection / Insulin S / Actrapid MC.
- Intermediate-acting insulins — e.g., isophane insulin HM; isophane insulin.
- Long-acting / prolonged-acting insulins — e.g., insulin glargine, insulin detemir, Ultratard HM.
What is the full mechanism of action of GLP-1 receptor agonists?
The mechanism of action of GLP-1 receptor agonists includes a complex effect on metabolism and digestion:
- Glucose-dependent stimulation of insulin secretion — enhanced insulin production in response to glucose.
- Reduction of glucagon secretion — glucose-dependent suppression, leading to decreased hepatic glucose production.
- Delayed gastric emptying — contributes to reducing postprandial glycemia.
- Reduced food intake — leads to weight loss and reduced insulin resistance.
- Reduction of de novo lipogenesis — accompanied by a decrease in serum transaminase levels.
To avoid confusing the mechanisms of oral agents: Biguanides = Beta-cell-independent (only increase sensitivity), while Sulfonylureas = Secretion of insulin.
Class and exam questions
How exactly does insulin force cells to take up glucose?
After binding to specific receptors, insulin triggers the translocation of GLUT-4 carrier proteins from the cytoplasm to the cell membrane. Once on the surface, these carriers actively uptake glucose into adipose and muscle tissue.
What is the fundamental difference between biguanides and sulfonylureas?
Sulfonylureas directly stimulate pancreatic beta cells, forcing them to release more insulin. Biguanides, on the other hand, do not affect secretion, but combat insulin resistance by increasing tissue sensitivity to the hormone.
Why does acarbose treatment often cause abdominal bloating?
Acarbose blocks enzymes that break down carbohydrates in the small intestine. As a result, unfermented sugars reach the large intestine, where local microflora begin to actively ferment them with abundant gas production.
Why are glucagon preparations used in diabetology?
Glucagon is a physiological antagonist of insulin and belongs to hyperglycemic agents. It is administered in emergency situations to rapidly increase blood sugar levels and manage severe hypoglycemia.
What else to study on this topic
- Mechanism of action of flozins (SGLT2 inhibitors) and renal glucose excretion.
- Pharmacokinetics and side effects of sulfonylureas.
- Differences in the mechanisms of action of GLP-1 agonists and DPP-4 inhibitors.
- Intracellular reaction cascade upon insulin receptor activation.
- Specifics of using insulin preparations in type 2 diabetes mellitus.
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