Type 2 Diabetes MellitusPhase 4NCT04014192
Effects of SGLT2 Inhibitors on Islet Cell Function and Insulin Sensitivity in Patients of Type 2 Diabetes Mellitus
A Phase 4 study testing Dapagliflozin, Empagliflozin and Canagliflozin in people with Type 2 Diabetes Mellitus, run by Peking Union Medical College Hospital at 1 site in China.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- Dapagliflozin, Empagliflozin and Canagliflozin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Sep 2019to 31 Jul 2020
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- (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.
Who cannot join
- (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.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Peking Union Medical College Hospital
Beijing, Beijing Municipality, 100730
Weigang Zhao, MD, +86 13910054636, xiehezhaoweigang@163.com
Tao Yuan, MD, +86 13671067042, t75y@sina.com
About this study
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.
Read the detailed description
In this study, type 2 diabetes patients were treated with three kinds of SGLT2 inhibitors (dapagliflozin, empagliflozin and canagliflozin) for one week. With routine dose applied, (dapagliflozin 10mg/d, empagliflozin 10mg/d, canagliflozin 100mg/d), blood glucose level could be improved with small expected effect on body weight and no effect in lipid metabolism after the treatment period of one week. Normal glucose tolerance subjects (diagnosed of OGTT) were included as the control group.According to previous studies in three major SGLT2 inhibitors currently on the market, an increase in urinary glucose excretion and a decrease in blood glucose within three days after application in mice and human could be observed. Therefore, the short-term treatment cycle in this study is intended to be set at one week, and can be extended to two weeks if there is no significant decrease in blood glucose.
The insulin sensitivity, islet beta cell secretion function and islet alpha cell function of diabetic patients were measured at baseline (before taking SGLT2 inhibitors) and one week after taking SGLT2 inhibitors, of normal glucose tolerance subjects were measured only at baseline. The effect of SGLT2 inhibitors on islet cell function and insulin sensitivity would be evaluated in order to study the extrarenal action mechanism of SGLT2 inhibitors.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- Dapagliflozin, Empagliflozin, Canagliflozin
- Keywords
- Sodium and Glucose Synergistic Transporter 2 Inhibitor, Beta Cell Function, Alpha Cell Function, Insulin Sensitivity
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DapagliflozinDrug
Treated with dapagliflozin 10mg/d for one week.
EmpagliflozinDrug
Treated with empagliflozin 10mg/d for one week.
CanagliflozinDrug
Treated with canagliflozin 100mg/d for one week.
| Study group | Role | What they receive |
|---|---|---|
| Dapagliflozin Group | Experimental | 10mg/d for one week Receives: Drug: Dapagliflozin |
| Empagliflozin Group | Experimental | 10mg/d for one week Receives: Drug: Empagliflozin |
| Canagliflozin Group | Experimental | 100mg/d for one week Receives: Drug: Canagliflozin |
| Normal Glucose Tolerance Group | No intervention | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
Change from baseline to post-treatment in fasting insulin level.
Measured: 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.
Measured: 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.
Measured: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
Change from baseline to post-treatment in urinary output of uric acid, sodium, calcium, and phosphorus.
Measured: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jul 2019
- Study start1 Sep 2019
- Primary completion31 Jul 2020 (estimated)
- Study completion31 Jul 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 2 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Peking Union Medical College HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking Union Medical College Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04014192
- Sponsor's protocol ID
- Yuan-SGLT2
- Status last verified
- Aug 2019
- First submitted
- 7 Jul 2019
- Last updated
- 24 Sep 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 33117454
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of SGLT2 Inhibitors on Islet Cell Function and Insulin Sensitivity in Patients of Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT04014192
- Acronym / sponsor ID
- Yuan-SGLT2
- Conditions
- Type 2 Diabetes Mellitus
- Keywords
- Sodium and Glucose Synergistic Transporter 2 Inhibitor, Beta Cell Function, Alpha Cell Function, Insulin Sensitivity
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Peking Union Medical College HospitalUniversity, hospital or other
- Study start
- 1 Sep 2019 (actual)
- Primary completion
- 31 Jul 2020 (estimated)
- Study completion
- 31 Jul 2020 (estimated)
- First posted
- 10 Jul 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
In this study, type 2 diabetes patients were treated with three kinds of SGLT2 inhibitors (dapagliflozin, empagliflozin and canagliflozin) for one week. With routine dose applied, (dapagliflozin 10mg/d, empagliflozin 10mg/d, canagliflozin 100mg/d), blood glucose level could be improved with small expected effect on body weight and no effect in lipid metabolism after the treatment period of one week. Normal glucose tolerance subjects (diagnosed of OGTT) were included as the control group.According to previous studies in three major SGLT2 inhibitors currently on the market, an increase in urinary glucose excretion and a decrease in blood glucose within three days after application in mice and human could be observed. Therefore, the short-term treatment cycle in this study is intended to be set at one week, and can be extended to two weeks if there is no significant decrease in blood glucose.
The insulin sensitivity, islet beta cell secretion function and islet alpha cell function of diabetic patients were measured at baseline (before taking SGLT2 inhibitors) and one week after taking SGLT2 inhibitors, of normal glucose tolerance subjects were measured only at baseline. The effect of SGLT2 inhibitors on islet cell function and insulin sensitivity would be evaluated in order to study the extrarenal action mechanism of SGLT2 inhibitors.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Dapagliflozin Group | Experimental | Drug: Dapagliflozin10mg/d for one week |
| Empagliflozin Group | Experimental | Drug: Empagliflozin10mg/d for one week |
| Canagliflozin Group | Experimental | Drug: Canagliflozin100mg/d for one week |
| Normal Glucose Tolerance Group | No intervention | – |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- (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.
Key exclusion criteria (7 listed)
- (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].
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DapagliflozinTreated with dapagliflozin 10mg/d for one week. | Drug | Dapagliflozin Group |
| EmpagliflozinTreated with empagliflozin 10mg/d for one week. | Drug | Empagliflozin Group |
| CanagliflozinTreated with canagliflozin 100mg/d for one week. | Drug | Canagliflozin Group |
Primary outcome
Change from baseline to post-treatment in insulin sensitivity.
Time frame: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
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
Change from baseline to post-treatment in islet beta cell secretory function.
Time frame: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
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)
Change from baseline to post-treatment in islet alpha cell secretory function.
Time frame: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
Islet Alpha Cell secretory function is calculated by area under the curve of blood glucose、glucagon level in OGTT.
6 secondary outcomes
Change from baseline to post-treatment in weight.
Time frame: 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.
Time frame: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
Change from baseline to post-treatment in fasting insulin level.
Time frame: 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.
Time frame: 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.
Time frame: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
Change from baseline to post-treatment in urinary output of uric acid, sodium, calcium, and phosphorus.
Time frame: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Derived from this study: PubMed 33117454Yuan 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Dapagliflozin, Empagliflozin and Canagliflozin in people with Type 2 Diabetes Mellitus, run by Peking Union Medical College Hospital at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Weigang Zhao, MD (+86 13910054636, xiehezhaoweigang@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline to post-treatment in insulin sensitivity. (time frame: Baseline, Week 1(extended to Week 2 if without significantly decrease in blood glucose)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04014192, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2019; AzTrials last refreshed its copy on 6 Nov 2026.