The Role of SGLT2 Inhibitors and GLP-1 agonists in the Treatment of Diabetes

Introduction

“I don’t want to exercise if I can have a good meal without gaining weight,” said Elon Musk, the founder of Tesla, who said what all women dream of. Tasting food is one of the best things in life, and who can resist the temptation when food is in front of them?

As human society shifts from agriculture to industry to the current commercial generation, diets are becoming more abundant and refined, and diabetes has become a national disease. According to the International Diabetes Federation (IDF), the total number of people with diabetes in the world will reach a new high of 7.8 billion in 2045. Diabetes has been one of the top 10 causes of death in China. According to the 2019 Diabetes Yearbook of the National Institutes of Health, there are about 2.3 million people with diabetes in Taiwan, and the number continues to grow at a rate of 25,000 per year, which will become a major killer of health care resources if left unattended.

The good news is that although diabetes is one of the top 10 causes of death, it is not an incurable disease. Many pharmaceutical companies are looking at the business opportunities of diabetes and have developed various kinds of drugs to control blood sugar. Among them, SGLT2 Inhibitor and Glp-1 analog have been frequently mentioned in the past few years, and so far, clinical trials of different drug companies for different groups are still in full swing.

In 2021, the EMPEROR Trial noted that SGLT2 inhibitors have a place in the treatment of heart failure in addition to lowering glucose, opening up a whole new field of opportunities for SGLT2 inhibitors to add new indications. Moreover, Glp-1 analogs are also making their way into the self-financed market, taking advantage of weight loss opportunities. Next, we will briefly introduce SGLT2 Inhibitor and Glp-1 analog, two of the more popular hypoglycemic drugs in recent years.

SGLT2 Inhibitor

Mechanism

There are many ion-transport receptors in the human kidney, including the SGLT1 receptor and SGLT2 receptor located in the proximal tubule. The SGLT1 receptor is responsible for recycling 10% of the glucose that enters the body, while the SGLT2 receptor is responsible for recycling 90% of the glucose that enters the body, which indicates that the SGLT2 receptor plays an important role in glucose absorption in the body.

SGLT receptors recycle both glucose and sodium. Therefore, if SGLT receptors are inhibited, glucose recycling in the kidneys will be reduced, which in turn will lower blood glucose. Because SGLT2 is responsible for recycling 90% of the glucose entering the body, SGLT2 is currently used as the target of diabetes medication.

According to clinical observation, SGLT2 inhibitors can excrete about 78 grams of glucose per day, which is about the sugar content of two 500ml glasses of milk. It also has a hypotensive effect because it excretes sodium ions at the same time. It is worth mentioning that taking SGLT2 inhibitors for six months can lower HbA1c by 0.8 to 1.0% on average.

Commercially available SGLT2 inhibitor

The following table briefly summarizes the more common commercially available SGLT2 inhibitors for your reference.

Trade name	Academic Name	Dosage
Jardiance	Empagliflozin	25mg
Forxiga	Dapagliflozin	10mg
Canaglu	Canagliflozin	100mg
Steglatro	Ertugliflozin	5mg
Glyxambi	Empagliflozin/Linagliptin	25/5mg
Qtern	Dapagliflozin/Saxagliptin	5/10mg

Side effects

Although SGLT2 inhibitors are effective in removing sugar, there are still side effects to be aware of. Common side effects of SGLT2 inhibitors include: genitourinary tract infection, dehydration, risk of hypotension, diabetic ketoacidosis, nausea, muscle pain, etc. The most common side effects are genitourinary tract infections, so it is important to advise patients to drink more water to help reduce the occurrence of side effects and improve their quality of life.

Glp-1 agonist

Mechanism

GLP-1 agonists are found in the saliva of the Gila Monster, a venomous lizard that lives in the desert. Gila Monster is a large, slow-moving lizard that eats only once or twice a year and uses the secretion of its salivary hormone Exendin-4 (a hormone with similar properties to GLP-1, sharing 53% of its amino acid sequence) to induce the proliferation of the pancreas and intestine to facilitate food absorption. It is this efficiency in food breakdown and absorption that has made GLP-1 agonists a target for drug development.

If you are interested in knowledge of reptiles, you can also click to see this article below!

Two fragments of GLP-1, 7-37 and 7-36, were found to be effective regulators of insulin gene expression and insulin secretion. Further studies have shown that GLP-1 plays a role in the protection of pancreatic β-cell function. Therefore, GLP-1 agonists not only stimulates insulin secretion, but also inhibits β-cell apoptosis and maintains blood glucose stability in humans. In fact, GLP-1 agonists have a wide range of effects on human organ systems, including cardiac muscle, neurons, weight control, and energy expenditure. For this reason, there is currently a clinical Off-Label-Use for self-funded weight loss.

Commercially available GLP-1 agonists

The following table summarizes the commercially available GLP-1 agonists for your reference.

Academic Name	Trade name	Frequency of injections
Liraglutide	Victoza	The starting dose is 0.6 mg once daily, and the dose should be increased by 0.6 mg at intervals of at least one week to 3.0 mg once daily
Dulaglutide	Trulicity	The starting dose is 0.75 mg once a week, which may be increased to 1.5 mg once a week for better glycemic control.
Semaglutide	Ozempic	Starting dose of 0.25 mg once a week for four weeks, once a week

Side effects

Common side effects of GLP-1 agonists include nausea, diarrhea, vomiting, dehydration and dizziness. Acute pancreatitis and deterioration of kidney function are relatively rare but serious side effects. It is important to note that patients with medullary thyroid cancer and type 2 multiple endocrine neoplasia syndrome are contraindicated.

Conclusion

Recently, famous beverage companies and lasagna makers have been offering chestnut flavors to grab the business opportunities in autumn. After all, lifestyle modification is also very important. I hope you can maintain your health and avoid becoming a risk group for diabetes.

There is another type of medication for older frail patients with type 2 diabetes – DPP4i – but I’ll save that for another time.

References:

1. International Diabetes Federation. IDF🔗
2. The BJM-Incretin mimetics 🔗
3. Gila Monster Venom, Gut Hormones, and Diabetes: The Winding Path to Drug Discovery 🔗
4. DrugWatch-SGLT2 Inhibitors Side Effects 🔗
5. Micromedex
6. Image taken from pixabay