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In the last few decades, there have been a lot of great improvements in how type 2 diabetes (T2DM) is treated. Researchers are always looking for new ways to treat diseases. The area of T2DM research is now very interested in how to control blood sugar and reduce complications caused by diabetes.Before, The Lancet Diabetes Endocrinology released a detailed review about new therapeutic targets for T2DM, how drugs work, and how well they lower blood sugar. It requires coming up with new ideas since standard insulin and a lot of other new drugs are on the way.
The current state of T2DM treatment development
In the past few years, the number of people with T2DM has been rising quickly all over the world. It has become a major threat to public health all over the world. The main treatment for people with T2DM is hypoglycemic therapy. This is because the short-term goal of T2DM treatment is to reduce hyperglycemia. Patients with T2DM will also have a better quality of life and live longer if they change their lifestyle to be healthier and take other drugs to avoid complications from diabetes treatment.
It is important to note that a large number of new treatments have been used successfully. Such as continuous glucose tracking, insulin pumps, and oral hypoglycemic sodium-glucose co-transport protein 2 (SGLT2) inhibitors. With injectable glucagon-like peptide-1 (GLP-1) agonists, the number of people who have good control of their blood sugar has not gone up as predicted. Which may be affected by how easy it is to get drugs, how well patients are educated, and how motivated they are. This could be caused in part by things like how easy it is to get drugs, how well patients are educated, and how motivated they are to take their medications. New ways of treating T2DM, like making glucose-lowering drugs work better and reducing serious side effects like weight gain and diabetic hypoglycemia, could help solve the problem.
What's New in Treating Type 2 Diabetes?
Changes in how insulin is made
In 2021, insulin will have been around for 100 years. Scientists are still looking into different ways to take insulin, how to inject it, how well it works, and if it is safe.
Icodec insulin is a new basal insulin analog that works for a long time. It binds tightly but reversibly to albumin to lower blood sugar slowly and steadily. Patients with T2DM can get a dose of icodec insulin once a week. This is because the insulin is very concentrated. And it works the same way and is as safe as insulin U100 taken once a day.
In terms of "smart" insulin delivery, new findings include insulin analogs with a sugar-linked structure (like MK-2640) and subcutaneous insulin delivery devices that respond to blood sugar levels. The first one can connect to insulin receptors to lower blood sugar. Or it could connect to mannose receptors to break down and get rid of itself. The second one is based on glucose-responsive vesicles or phenylboronic acid-glucose complex gel microspheres, which can control how much insulin is released when blood sugar levels are too high. "Smart insulin" is where insulin research is going, but it is still in the early stages of research.
Insulin resistance is the new force that needs to be fought.
Adiponectin is a protein that fat cells release. It is closely linked to insulin resistance and being overweight. In vivo and in vitro tests have shown that adiponectin has anti-atherosclerotic, anti-diabetic, and anti-inflammatory benefits and can stop diabetes and cardiovascular diseases from getting worse. We want to point out that several studies are currently being done on Adiponectin and its derivatives, such as PPAR agonists. Different therapies have shown different amounts of glycemic reduction, but these studies are still in the preclinical stage.
Most of the fibroblast growth factor (FGF)-21 comes from the liver. It has been known for a long time that it is a metabolic factor that controls how fat and glucose are used and how sensitive insulin is. Most of the time, FGF-21 and its products cause Adiponectin to be released. Exogenous FGF-21 can still lower blood sugar and body weight in mice that are obese and resistant to insulin, according to tests done before they were put in people. At the moment, phase 1 and phase 2 clinical studies have shown that FGF21 and other drugs with similar structures work. Even though the effects on humans and animals are different, we are excited to learn more in the future.
In addition to adiponectin and hepatocyte factor FGF-21, the paper says Small-molecule oral GLP-1 receptor agonists, GLP-1 pro-secretory agents, and imeglimin, an innovative drug that targets mitochondrial bioenergetics, are also potential ways to treat T2DM. At the same time, it's hard to know how to treat T2DM without making people sick.
Small-molecule GLP-1 receptor agonists taken by mouth
GLP-1 agonists are a type of drug called an entero-insulin, which can help with more than just dropping blood sugar. Things like losing weight, having a lower systolic blood pressure, and having better lipid makeup. Studies like LEADER, SUSTAIN-6, and REWIND show that people with T2DM who take GLP-1 agonists may be less likely to have bad things happen to their kidneys.
Small-molecule oral GLP-1 agonists should be easier for diabetics to take. In preclinical animal models, small-molecule oral GLP-1 receptor agonists change the amounts of cAMP in islet cells in a way that depends on how much glucose is in the blood. This increases insulin secretion and lowers blood glucose, and the pharmacokinetic study results of these drugs in human trials are something to look forward to.
GLP-1 agents can also work by getting L cells in the intestine to make more GLP-1. And lab tests on animals have shown that GLP-1 agonist drugs can help animals with poor glucose tolerance.
Metformin is used as a starting point to make the small-molecule drug imeglimin. In Japan, the FDA said it could be used to treat T2DM. We think that Imeglimin will lower blood sugar by making it easier for pancreatic cells to release insulin. And it makes the body more sensitive to insulin, avoiding insulin resistance caused by a high-fat diet and stopping the liver from making glucose.
Also, bariatric surgery can change the hormone environment in the intestines. This means that single-molecule peptides that target multiple receptors (like GLP-1, glucose-dependent insulinotropic polypeptide, glucagon, or peptide YY) could be used. So, future studies may also focus on dual or triple single-molecule peptide agonists that target GLP-1 and other targets.
Innovative treatments that can only be used in certain situations
Based on what we know now, peroxisome proliferator-activated receptor (PPAR) agonists, glucagon receptor agonists, glucokinase activators, and inhibitors of the glucocorticoid metabolizing enzyme 11-hydroxysteroid dehydrogenase (11-HSD) are unlikely to be used in the clinic because the evidence of benefit and risk is not promising.
Individualized care of T2DM in the future
The article says that in the future, people with T2DM may choose glucose-lowering drugs based on their personal phenotype (for example, based on anthropometric or laboratory parameters) or even their genotype. Cluster analysis showed that the same cluster of T2DM patients were not only more or less likely to get certain complications of diabetes, But this group's diseases also move at different rates.
This shows that the main pathophysiological mechanisms of disease onset may be different for different people in the same subgroup, and that the best way to treat them may also be different. In the future, genetic traits of T2DM patients may be able to predict the effectiveness of certain diabetic drugs and the chance of side effects.
Conclusion
Scientists are working on ways to help diabetics better control their blood sugar levels. Through a number of creative ways, some of which are likely to work in the long run. It can change how T2DM is treated and taken care of.
The authors' team talked about smart insulin delivery agents, drugs that target poor mitochondrial function (like imeglimin), GLP-1 secretagogues, small-molecule oral GLP-1 receptor agonists, and single-molecule peptides that can interact with multiple endocrine hormone receptors at the same time. We hope to help people with T2DM a lot by lowering their blood sugar and keeping their weight in check. Also, treatments to improve risk factors and other health problems that are linked to T2DM may become more important.
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