Type 1 Diabetes Medications-Non-insulin Hypoglycemic

Type 1 diabetes is a difficult problem in the treatment of diabetes. At present, the glycemic control rate of Chinese patients with type 1 diabetes is less than half, and traditional insulin therapy for type 1 diabetes has side effects such as hypoglycemia events and weight gain. It has important clinical significance for the drug to help patients with type 1 diabetes meet the blood sugar safety target. This article mainly expounds the role of three types of type 1 diabetes medications including metformin, glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter inhibitors.

Metformin

The hypoglycemic mechanism of metformin is mainly to reduce hepatic glucose output by inhibiting gluconeogenesis. In China, the indications in the drug insert of metformin include type 1 diabetes, which is currently the only non-insulin hypoglycemic type 1 diabetes medications that can be used in China. However, in the standard of diagnosis and treatment of the American Diabetes Association, the only type 1 diabetes medications as an indication is pramlintide, and type 1 diabetes is not listed as an indication for metformin. Studies have found that when metformin is applied to patients with type 1 diabetes, the glycated hemoglobin can be decreased in the short term, but the long-term application may be due to insulin reduction, resulting in an insignificant decrease in glycated hemoglobin. In addition, long-term use of metformin can reduce body weight, and the slowing of carotid intima-media thickness thickening suggests a possible anti-atherosclerotic effect.

GLP-1 receptor agonists

GLP-1 can increase the biosynthesis and secretion of insulin, inhibit the secretion of glucagon, inhibit appetite and food intake, and delay the emptying of gastric contents. Native GLP-1 is rapidly degraded by dipeptidyl peptidase-4 in vivo, while GLP-1 receptor agonists are not degraded by dipeptidyl peptidase-4 and it can play a role by activating GLP-L receptor instead of physiological GLP-L. GLP-1 receptor agonists have the potential to exert hypoglycemic effects in patients with type 1 diabetes through non-insulin-dependent effects such as lowering glucagon or delaying gastric emptying. Current studies suggest that GLP-1 receptor agonists can reduce glycated hemoglobin in patients with type 1 diabetes, but the decrease in glycated hemoglobin gradually decreases with the prolongation of application time. Compared with placebo in long-term studies, the difference in glycated hemoglobin does not reach any 0.4% of clinically significant, limited absolute benefit. The weight-reducing effect of GLP-1 receptor agonists remains, but long-term data on their benefit in macrovascular complications are lacking.

SGLT-2 inhibitors

SGLT-2 is expressed in the proximal tubules of the kidney and mediates the reabsorption of nearly 90% of the filtered glucose load. SGLT-2 inhibitors promote renal excretion of glucose, thus lowering blood sugar levels. The mechanism of action of SGLT-2 inhibitors is non-insulin-dependent hypoglycemia, so it is considered to have application prospects in type 1 diabetes.

The InTandem3 trial is a study of soxagliflozin combined with insulin in type 1 diabetes. The results show that SGLT-2 inhibitors have a good and stable hypoglycemic effect in patients with type 1 diabetes, and retain weight loss, It has the advantages of benefiting from cardiovascular risk factors, but has the disadvantage of increasing the risk of diabetic ketoacidosis. Therefore, whether the incidence of diabetic ketoacidosis in patients with type 1 diabetes mellitus after using SGLT-2 inhibitors will definitely increase will become one of the key questions whether it can be safely used in clinical practice.

A 2018 meta-analysis applied continuous glucose monitoring to observe blood glucose fluctuations and found that the average blood glucose level, blood glucose standard deviation, and average blood glucose fluctuation range were reduced in the SGLT-2 inhibitor combined with insulin group, indicating that the application of SGLT-2 inhibitors can reduce blood glucose fluctuations. The decrease of blood sugar and the reduction of blood sugar fluctuations can make the blood sugar decrease without a significant increase in hypoglycemic events. Avoiding excessive reduction of insulin doses to avoid hypoglycemia may be one of the reasons why the glycated hemoglobin of patients in the SGLT-2 inhibitor group can continue to decline.

Summary

This article mainly discusses the efficacy of metformin, GLP-1 receptor agonists and SGLT-2 inhibitors in patients with type 1 diabetes. Although the above type 1 diabetes medications have the advantages of lowering blood sugar, reducing body weight, and reducing insulin dosage in clinical trials, only metformin has corresponding indications for type 1 diabetes in China, and the rest of type 1 diabetes medications are still in the exploratory stage, and need more research data to support.