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

NCT04014192 | Unknown Phase 4

• 1 other identifier: Yuan-SGLT2
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Type 2 Diabetes Mellitus

Keywords

Sodium and Glucose Synergistic Transporter 2 Inhibitor; Beta Cell Function; Alpha Cell Function; Insulin Sensitivity

Outcome Measures

Primary Outcomes (3)

• Change from baseline to post-treatment in insulin sensitivity.

  Insulin sensitivity is calculated by the following formula according to blood glucose and insulin levels in OGTT (Oral Glucose Tolerance Test). 1.1 OGTT Matsuda and De Fronzo Insulin Sensitivity Index（ISOGTT）：10000/square root(Gluc0×Ins0×mean Gluc×mean Ins)。Mean gluc and mean Ins are average values calculated by each value in 0, 60, 120 and 180 minutes of OGTT. 1.2 QUICKI（quantitative insulin sensitivity check index）model：1/(log\[Ins0\]+ log\[Gluc0\]) 1.3 HOMA-IR：(Gluc0×Ins0)/22.5

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

• Change from baseline to post-treatment in islet beta cell secretory function.

  Islet beta cell secretory function is calculated by area under the curve of blood glucose、 insulin、C-peptide in OGTT and following formula above. 2.1 Stumvoll first phase insulin secretion：1,194+4.724×Ins0-117.0 ×Gluc60 + 1.414×Ins60 2.2 Stumvoll second phase insulin secretion：295+0.349×Ins60-25.72×Gluc60+1.107×Ins0 2.3 HOMA-β：(20×Ins0)/(Gluc0-3.5)

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

• Change from baseline to post-treatment in islet alpha cell secretory function.

  Islet Alpha Cell secretory function is calculated by area under the curve of blood glucose、glucagon level in OGTT.

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

Secondary Outcomes (6)

• Change from baseline to post-treatment in weight.

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

• Change from baseline to post-treatment in fasting blood glucose and non-fasting blood glucose.

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

• Change from baseline to post-treatment in fasting insulin level.

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

• Change from baseline to post-treatment in blood lipid including cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol.

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

• Change from baseline to post-treatment in urine volume and urine glucose level.

  Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)

Study Arms (4)

Dapagliflozin Group

EXPERIMENTAL

10mg/d for one week

Drug: Dapagliflozin

Empagliflozin Group

EXPERIMENTAL

10mg/d for one week

Drug: Empagliflozin

Canagliflozin Group

EXPERIMENTAL

100mg/d for one week

Drug: Canagliflozin

Normal Glucose Tolerance Group

NO INTERVENTION

Interventions

Dapagliflozin DRUG

Treated with dapagliflozin 10mg/d for one week.

Dapagliflozin Group

Empagliflozin DRUG

Treated with empagliflozin 10mg/d for one week.

Empagliflozin Group

Canagliflozin DRUG

Treated with canagliflozin 100mg/d for one week.

Canagliflozin Group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• (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.

Sponsors & Collaborators

• Peking Union Medical College Hospital: lead

Study Sites (1)

Peking Union Medical College Hospital

Beijing, Beijing Municipality, 100730, China

RECRUITING

Related Publications (1)

• Yuan T, Liu S, Dong Y, Fu Y, Tang Y, Zhao W. Effects of dapagliflozin on serum and urinary uric acid levels in patients with type 2 diabetes: a prospective pilot trial. Diabetol Metab Syndr. 2020 Oct 27;12:92. doi: 10.1186/s13098-020-00600-9. eCollection 2020.

  PMID: 33117454 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Interventions

dapagliflozin; empagliflozin; Canagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Glucosides; Glycosides; Carbohydrates

Central Study Contacts

Weigang Zhao, MD

CONTACT

+86 13910054636; xiehezhaoweigang@163.com

Tao Yuan, MD

CONTACT

+86 13671067042; t75y@sina.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 7, 2019
• First Posted: July 10, 2019
• Study Start: September 1, 2019
• Primary Completion: July 31, 2020
• Study Completion: July 31, 2020
• Last Updated: September 24, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)