Effects of SGLT2 Inhibitors on Islet Cell Function and Insulin Sensitivity in Patients of Type 2 Diabetes Mellitus

• Status: Unknown status
• Trial end date: 2020-07-31
• Target enrollment: 0
• Participant gender: All

Summary

The main pathogenesis of type 2 diabetes mellitus is insulin resistance and insufficient secretion of insulin by pancreatic beta cells. SGLT2 (sodium-glucose synergistic transporter 2) inhibitor is a kind of newly developed hypoglycemic medicine, which increases urinary glucose excretion and lowers blood glucose in an insulin-independent manner. The mechanisms of its effects on insulin resistance, insulin secretion by pancreatic beta cells and glucagon secretion by pancreatic alpha cells, are not well studied in domestic and foreign, and there is no unified conclusion. A few studies concerning SGLT2 inhibitors have observed that insulin resistance and islet beta cell secretion function can be improved by the improvement of glucotoxicity and lipotoxicity, but its effect on pancreatic alpha cell function to increase glucagon level, thereby increasing liver glucose output, may be one of the mechanisms of its side effects. In this study, patients with type 2 diabetes mellitus were treated with three domestic listed SGLT2 inhibitors (dapagliflozin, empagliflozin and canagliflozin) for one week, which were expected to improve the glucotoxicity, but excluding the effects on lipotoxicity and body weight, to observe the changes of islet beta cell and alpha cell function and insulin sensitivity. Three different SGLT2 inhibitors were used in order to make clear whether this effect is the unique effect of different structure of drugs or the similar effect of this kind of drugs.

• Phase: Phase 4
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Peking Union Medical College Hospital
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Canagliflozin; Dapagliflozin; Empagliflozin; Insulin; Sodium-Glucose Transporter 2 Inhibitors

Criteria

Inclusion Criteria:

• (1)According to the diagnostic criteria of World Health Organization (WHO) in 1999, type 2 diabetes mellitus was diagnosed clinically. The age ranged from 18 to 70 years (including 18 and 70 years). There was no limit to the duration of diabetes mellitus and gender.

• (2)Basic antidiabetic therapy is not limited.

• (3)HbA1c ≥ 7%.

• (4)eGFR ≥60 ml/min；without contraindications to SGLT2 Inhibitors.

• (5)Sign written consent form voluntarily.

Exclusion Criteria:

• (1)Other types of diabetes mellitus.

• (2)Unstable control of blood glucose(fasting blood glucose > 11.1 mmol/L).

• (3)Acute complications of diabetes mellitus within 6 months.

• (4)History of myocardial infarction or stroke within 6 months, or existing severe cardiovascular disease and risk.

• (5)Abnormal liver function [i.e. serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) is 1.5 times higher than the upper limit of normal value].

• (6)Severe hypertension that defined as systolic blood pressure ≥160 mmHg, diastolic blood pressure ≥90 mmHg with drug therapy, or hypotension (resting seat blood pressure < 90/50 mmHg).

• (7)psychosis, alcohol dependence or history of drug abuse, lactation women, participation in other studies three months before the trial, allergic constitution or allergic to a variety of drug and those researchers think inappropriate to the research.