DPP-4 Inhibitors in the Management of Diabetes

In the realm of Diabetes management, advancements are continually being made to offer patients effective and safe treatment options. Among these innovations are DPP4 inhibitors, a class of medications proving   to be a valuable addition to the          arsenal against Diabetes.

Before delving into DPP4 inhibitors, let us first see two important aspects.

What is Diabetes, and what are the hormones which affect glucose control?

Diabetes mellitus (DM) refers to uncontrolled blood glucose levels, which is seen when pancreas (a gland in our body, located behind the stomach, which produces hormones and digestive enzymes) is not able to produce adequate insulin or when the insulin is not able to work as intended, or both. There are other forms also, discussion of which is beyond the scope of this article.

Insulin and glucagon are both hormones produced by the pancreas, and are vital for regulating glucose metabolism in the body.

Insulin:

. Insulin is released by the pancreas when blood sugar levels rise, such as after eating a meal containing carbohydrates.

. Its primary role is to facilitate the uptake of glucose from the bloodstream into cells, particularly muscle and fat cells. This helps to lower blood sugar levels and provide energy to cells for various functions.

. Insulin also promotes the storage of excess glucose in the liver and muscles in the form of glycogen. It inhibits the breakdown of glycogen (glycogenolysis) and stimulates the synthesis of new glycogen (glycogenesis).

. Additionally, insulin plays a role in promoting the synthesis of fats (lipogenesis) and inhibiting the breakdown of fats (lipolysis).

. Glucagon is released by the pancreas when blood sugar levels are low, such as between meals or during periods of fasting.

. Its primary role is to raise blood sugar levels by stimulating the breakdown of glycogen stored in the liver (glycogenolysis) and the synthesis of new glucose from non-carbohydrate sources, such as amino acids (gluconeogenesis).

. Glucagon also promotes the release of fatty acids from fat cells (lipolysis), which can be used as an alternative energy source when glucose is limited.

Together, insulin and glucagon work in concert to maintain blood sugar levels within a narrow range ensuring that cells have a constant supply of energy for their metabolic needs.

Now, let's delve into the main hero of this article, DPP4 inhibitors, short for dipeptidyl peptidase-4

inhibitors, also known as gliptins, belong to a class of oral anti-Diabetes medications designed to lower blood glucose levels in individuals with type 2 Diabetes mellitus.

How do these medications work?

They work by blocking the action of the enzyme DPP4 (dipeptidyl peptidase-4), which is responsible for breaking down incretin hormones. The primary incretins involved are glucagon-like peptide-1 (GLP-

1)  and glucose-dependent insulinotropic polypeptide (GIP). These hormones play a crucial role in regulating blood glucose levels by stimulating insulin release and inhibiting glucagon secretion after meals. By inhibiting DPP4, these medications prolong the action of incretin hormones, thereby enhancing their glucose-lowering effects.

 Key benefits

One of the key advantages of DPP4 inhibitors is their mechanism of action, which operates in a glucose-dependent manner. This means that they primarily work when blood sugar levels are elevated, minimizing the risk of hypoglycemia, or low blood glucose, which is a common concern with some other Diabetes medications. This characteristic makes DPP4 inhibitors particularly suitable for individuals who are prone to low blood sugar levels or those who require tighter control over their blood sugar levels. DPP-4 inhibitors have been shown to effectively lower HbA1c levels by approximately 0.5-1.0 per cent when used as alone or in combination with other antidiabetic medications.

Additionally, DPP4 inhibitors offer several other benefits beyond glycemic control. Studies have suggested potential benefits on heart and, they have been  found to reduce the degree of inflammation. Furthermore, some DPP4 inhibitors have demonstrated favorable effects on weight and blood pressure, which are significant factors in Diabetes management and overall cardiovascular health.

Several DPP4 inhibitors are currently available on the market, each with unique characteristics and considerations of its own. Among the most commonly prescribed are Sitagliptin, Vildaglipitin, Linagliptin, Tenegliptin, Saxagliptin, Evogliptin and Alogliptin. These medications vary in terms of how many times they must taken per day, upon the kidney functioning, and on their  interactions with other medications, making it essential for healthcare providers to tailor treatment regimens to individual patient needs and medical histories.

Side effects

Like any medication, DPP4 inhibitors may be associated with certain side effects, although they are generally well-tolerated. Common side effects may include headache, infections involving nose and throat, and tummy disturbances such as vomiting/feeling sick and loose motions. Serious side effects such as pancreatitis (problem with the pancreas which causes tummy pain, vomiting, and can be a serious medical condition) and allergic reactions are rare but require prompt medical attention if they occur.

It is important for individuals with Diabetes to work closely with their healthcare providers to determine the most appropriate treatment approach for their condition. While DPP4 inhibitors offer significant advantages in terms of safety and efficacy, they are most effective when used as part of a comprehensive Diabetes management plan that includes lifestyle modifications such as diet and exercise.

In conclusion, DPP4 inhibitors represent a valuable therapeutic option for individuals with type 2 Diabetes, offering effective glycemic control with a favorable safety profile. With ongoing research and continued advancements in Diabetes care, these medications continue to play a pivotal role in improving the lives of patients living with this chronic condition.

Dr Ankur Sharma is Consulting Diabetologist