Type 2 Diabetes MellitusNCT02846233
Stepping-down Approach in Patients With Chronic Poorly-controlled Diabetes on Advanced Insulin Therapy?
A study testing GLP1 receptor agonist, basal insulin and SGLT2 inhibitor in people with Type 2 Diabetes Mellitus, run by University of California, San Francisco at 1 site in United States.
Trial summary
In traditional step-up approach, the patients with poorly-controlled type 2 diabetes are instructed to take up to 4 insulin injections daily or multiple daily injections (MDI) as the most advanced therapy. However, a significant number of these patients continue to have poor diabetes control. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Type 2 Diabetes Mellitus
- What is being tested?
- GLP1 receptor agonist, basal insulin and SGLT2 inhibitor
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2016to Dec 2018
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- The following patients with diabetes mellitus type 2 who can give written consent will be eligible for enrollment. They must meet all criteria.
- > 21 years of age
- Body mass index (BMI) ≥30 kg/m2
- On insulin at least 2 times daily comprising both a basal and a prandial insulin or a pre-mix insulin with or without other non-insulin medications for a least past 3 months
- A1c >8%
- eGFR >45%
Who cannot join
- The patients with any of the following criteria will be excluded.
- Any patient who does not meet the above inclusion criteria.
- Pregnancy
- Patients who are on a SGLT2i and a GLP1 RA injection at the time of enrollment.
- diabetes mellitus type 1
- C-peptide below normal range if measured in the past.
Show all 11Show fewer
- patients with a history of diabetes ketoacidosis
- A history of recent and frequent (≥ 2 times within past 3 months) urinary tract infection or genito-urinary candidiasis requiring antibiotic and/or anti-fungal therapies.
- a personal or family history of medullary thyroid carcinoma (MTC) or in patients with Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- eGFR <45%
- patients with a history of acute pancreatitis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Is the Stepping-down Approach a Better Option Than Multiple Daily Injections in Patients With Chronic Poorly-controlled Diabetes on Advanced Insulin Therapy?
In traditional step-up approach, the patients with poorly-controlled type 2 diabetes are instructed to take up to 4 insulin injections daily or multiple daily injections (MDI) as the most advanced therapy. However, a significant number of these patients continue to have poor diabetes control. The most common reason is the noncompliance with multiple injections and the patient's reluctance to accept insulin-induced weight gain. More recently, the algorithm in diabetes management has significantly changed to accommodate the newer generation of medications. Addition of the diabetes medications, that can induce weight loss such as oral Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors and once-weekly glucagon-like peptide (GLP)-1 receptor agonists (GLP1 RA) injection, to a basal insulin is now recommended before the patient is advanced to MDI. This approach works very well in most patients since weight loss gives the patients an extra motivation to take medication regularly. Similarly, the patient does not require to take an insulin injection before each meal throughout the day in this approach.
Unfortunately, there are still a large number of patients with poor glycemic control who are still on MDI. Some of them were initiated on MDI before the availability of newer generations of medications. Some were started simply because the physician was not aware of or not the familiar with the new recommendations. Regardless of the reason, these patients are likely to remain on MDI despite chronic poor glycemic control since the physicians are understandably reluctant to step down the most advanced insulin therapy. In addition, there has been no data on the benefits and safety of the stepping-down approach from the most advanced insulin therapy to the more patient-friendly approach that is the combined use of oral SGLT2i and once-weekly GLP1 RA injection.
Read the detailed description
A prospective, randomized, open-label, controlled, parallel-group trial is planned. This study is an interdepartmental collaborative study among the Department of Internal Medicine, Department of Family \& Community Medicine (UCSF Fresno), Sierra Vista Family Medicine Residency Program and Division of Endocrinology.
The study will be conducted at the following multiple locations in order to maximize the patient recruitment:
- Internal medicine clinic at Derian Koligian ambulatory care center (ACC)
- Family practice medicine clinic at ACC
- Diabetes clinic at ACC
- Internal medicine clinic at University Medicine Associates in East medical Plaza
- Endocrine clinic at University Medicine Associates in East medical Plaza
- Sierra Vista clinics
The patients will be recruited during the first 12 months of the study or until the predetermined sample size is reached, whichever comes first.
The patient's primary care provider will be informed of the enrollment in the study if the participant gives the permission to do so.
All participants in both group will need to make all 3 visits to UCSF Clinical Research Center over 16- week period.
(1) First visit: Once the site co-investigators identify the suitable and interested study patient, a trained research coordinator will contact the patient for the first visit. The patient will be seen at the UCSF Clinical Research Center by the research coordinator and a physician co-investigator.
During the first visit, all patients in both group will
- be given the information about the study.
- sign the consent form.
- be randomly assigned to either treatment (i.e. Step Down) or control (MDI) group by using A Randomization Plan from http://www.randomization.com.
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ).
Medication changes at first visit:
In treatment group,
- All prandial insulin injections (Humalog, Novolog, Apidra, Novolin R or Humulin R), usually 3 times daily before meals, will be discontinued.
- Basal insulin (NPH, Lantus, Levimir, Toujeo or Tresiba), usually once daily at bed time, will be continued at 80 % of the home dose. The dose will be gradually increased until the patient is back on the home dose (the dose that the patient has been taking at home prior to the enrollment) or fasting BG of 80-130mg/dl is achieved by using the self-titration regimen.
- If the patient is on pre-mixed basal+prandial insulin 2-3 times daily, it will be discontinued and a basal insulin alone, (NPH, Lantus, Levemir, Toujeo or Tresiba), will be given at 40% of total daily dose of pre-mixed insulin. The dose will be gradually increased until fasting BG of 80-130mg/dl is achieved by using the self-titration regimen.
- Metformin, that most patients are expected to be on, will be continued, but other non-insulin oral medications for diabetes will be discontinued. If the patient is not on metformin, then Metformin ER will be started at 500mg with a meal for 2 weeks as a routine care and then 1000mg daily as a maintenance dose if tolerated.
- Both SGLT2i and GLP1 RA will be added to metformin and a basal insulin.
The patient will be trained on the injection technique of the once-weekly GLP1 RA, potential side effects, risk and benefits of all new medications in detail, hypoglycemia management and the self-titration regimen for the basal insulin.
In the control group, there will not be any change in MDI therapy, and the participants will continue to have the usual and standard care through the primary care provider. The participants should not receive SGLT2i and GLP1 RA during the study period.
(2) Second visit: At 4 weeks after the patient starts taking new medications, the patients will make the 2nd visit to the UCSF Clinical Research Center.
During the 2nd visit, the patient in the treatment group will
- be enquired about any side effect of the medications.
- be reviewed on insulin dose and the use of self-titration regimen for the basal insulin.
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ).
In the control group, there will not be any change in MDI therapy, and the participants will continue to have the usual and standard care through the primary care provider. The participants should not receive SGLT2i and GLP1 RA during the study period.
During the 2nd visit, the patient in the control group will
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ). (3) Third visit: The patients will make the 3rd or final visit to the UCSF Clinical Research Center at 12 weeks after 2nd visit or 16 weeks from the date of the start of both SGLT2i and a GLP1 RA.
During the 3rd visit, the patients in both groups will
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ).
The investigators will try to make a clinic appointment with primary care provider one month prior to the last visit to the research center for those who are in the treatment group if the patient gives the permission to do so. Therefore the primary care provider will be able to order the medications through the patient's health insurance plan if the patient wishes to remain on the study medications beyond the study period. Alternatively, the patients can go back on insulin therapy that was given prior to the study.
Monitoring of the treatment group:
The patients in both groups will monitor FPGs daily at minimum. The research coordinator will call all participants in both groups at weeks 1, 2, 8, and 12 to review fasting glucose measurements, ask for possible adverse events, incidents of hypoglycemia, and any change in medication.
All participants in both groups in both groups will be reviewed again at the UCSF Clinical Research Center at weeks #4 and #16 for both blood tests and physical examinations.
Outcome measurements:
The primary outcome is the change in A1c at the end of 16 weeks of study period and secondary outcomes are the changes in fasting blood glucose, weight, blood pressure, heart rate, fasting lipids, serum sodium and potassium, serum creatinine, liver enzymes, CBC, medication adherence scores and treatment satisfaction scores . These changes will be compared between the two independent groups, namely the treatment group and the control group, and also within the same group.
Blood test and questionnaire:
The following blood work will be drawn and analyzed at the community regional medical center at baseline (first visit), at 4 weeks and at the end of the study at 16 weeks:
- A1c
- Complete Blood Count (CBC) with differential
- Complete metabolic panel (CMP)
- Fasting lipid profile
Patient satisfaction with treatment in both groups will be measured by the validated the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form.
Patient adherence will be determined by using the Brief Medication Questionnaire (BMQ).
SAMPLE SIZE AND ANALYSIS PLAN:
The investigators will attempt to recruit and consent 20 patients in each arm that was calculated to provide an 80% statistical power at a 0.05 alpha in this continuous endpoint, two independent sample study.
The calculation was based on the following:
A mean Hemoglobin A1c of 8.5±1% at the initiation of the study period. In the treatment group we anticipate a decline in Hemoglobin A1c of 12-15% by the end of the study period. The standard deviation for the mean A1c was derived from the literature.
The data will be analyzed by using SPSS software. Significance testing will be conducted at the two-sided 5% level. Continuous variables will be examined for normality and if assumption is met, differences in mean values will be tested using Student's t test an analysis of variance (ANOVA). If not normally distributed, non-parametric procedures will be used, including Wilcoxan rank Sum test. Categorical data will be analyzed using Fisher's exact test and Chi square analysis. Since before/after comparisons will also be performed on the same study patients we will utilize paired t tests and McNemar's chi-square test.
- Conditions
- Type 2 Diabetes Mellitus
- Being tested
- GLP1 receptor agonist, basal insulin, SGLT2 inhibitor, Metformin
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GLP1 receptor agonistDrug
Also called Albiglutide (Tanzeum) or , Dulaglutide (Trulicity)
"Albiglutide or Dulaglutide" will be added to a basal insulin.
basal insulinDrug
Also called Lantus, Toujeo, NPH, levemir
The participant will continue with the basal insulin.
SGLT2 inhibitorDrug
Also called Empagliflozin (Jardiance)
"Empagliflozin" will be added to a basal insulin.
MetforminDrug
The participant will continue with metformin.
| Study group | Role | What they receive |
|---|---|---|
| Treatment group | Active comparator | Interventions: All prandial insulin injections, usually 3 times daily before meals, will be discontinued. Basal insulin, usually once daily at bed time, will be continued at 80 % of the home dose. Albiglutide OR Dulaglutide AND Empagliflozin will be added to metformin and a basal insulin. Receives: Drug: GLP1 receptor agonist; Drug: basal insulin; Drug: SGLT2 inhibitor; Drug: Metformin |
| Control group | No intervention | Interventions: There will not be any change in insulin therapy, and they will continue to have the usual and standard care through the primary care provider. They should not receive SGLT2i and GLP1 RA during the study period. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in A1c at the End of Study Period
change in A1c (%) from baseline to end of study at 16 weeks
Measured: 16 weeks (from baseline to end of study at 16 weeks)
Secondary outcomes (7)
Changes in Weight
change (in pounds) from baseline to the end of study at 16 weeks
Measured: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Blood Pressure
change (mmHg) of systolic BP from baseline to the end of study at 16 weeks
Measured: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Heart Rate
change (beats/min) from baseline to the end of study at 16 weeks
Measured: 16 weeks
Changes in LDL
change (mg/dL) from baseline to the end of study at 16 weeks
Measured: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Total Cholesterol
change (mg/dL) from baseline to the end of study at 16 weeks
Measured: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Serum Creatinine
change (mg/dL) from baseline to the end of study at 16 weeks
Measured: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Treatment Satisfaction Scores (DM-SAT Total Score)
Patient satisfaction with treatment in both groups will be measured by the validated the Diabetes Medications Satisfaction Tool (DM-SAT). Response options range from 0="not at all satisfied" to 10="extremely satisfied" and a total score is calculated ranging from 0 to 100, with higher scores indicating more diabetes medication satisfaction.
Measured: 16 weeks (from baseline to end of study at 16 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2016 (estimated)
- Study startAug 2016
- Primary completionDec 2018
- Study completionDec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)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 University of California, San FranciscoThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Francisco
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- SOE NAING, MD, Principal investigator, UCSF - Fresno
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02846233
- Sponsor's protocol ID
- RDMSTEP
- Status last verified
- Oct 2020
- First submitted
- 19 Jul 2016
- Last updated
- 10 Nov 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Herman WH, Kalyani RR, Wexler DJ, Matthews DR, Inzucchi SE. Response to Comment on American Diabetes Association. Approaches to Glycemic Treatment. Sec. 7. In Standards of Medical Care in Diabetes-2016. Diabetes Care 2016;39(Suppl. 1):S52-S59. Diabetes Care. 2016 Jun;39(6):e88-9. doi: 10.2337/dci16-0003. No abstract available.
PubMed 27222560Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, DeFronzo RA, Einhorn D, Fonseca VA, Garber JR, Garvey WT, Grunberger G, Handelsman Y, Henry RR, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez GE; American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE). CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. Endocr Pract. 2016 Jan;22(1):84-113. doi: 10.4158/EP151126.CS. No abstract available.
PubMed 26731084Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.
PubMed 25011946
Study at a glance
From the registry record, last updated by the sponsor on 10 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Is the Stepping-down Approach a Better Option Than Multiple Daily Injections in Patients With Chronic Poorly-controlled Diabetes on Advanced Insulin Therapy?
- ClinicalTrials.gov ID
- NCT02846233
- Acronym / sponsor ID
- RDMSTEP
- Conditions
- Type 2 Diabetes Mellitus
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of California, San FranciscoUniversity, hospital or other
- Study start
- Aug 2016 (actual)
- Primary completion
- Dec 2018 (actual)
- Study completion
- Dec 2018 (actual)
- First posted
- 27 Jul 2016 (estimated)
- Results
- Posted 10 Nov 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In traditional step-up approach, the patients with poorly-controlled type 2 diabetes are instructed to take up to 4 insulin injections daily or multiple daily injections (MDI) as the most advanced therapy. However, a significant number of these patients continue to have poor diabetes control. The most common reason is the noncompliance with multiple injections and the patient's reluctance to accept insulin-induced weight gain. More recently, the algorithm in diabetes management has significantly changed to accommodate the newer generation of medications. Addition of the diabetes medications, that can induce weight loss such as oral Sodium-glucose Cotransporter-2 (SGLT2) Inhibitors and once-weekly glucagon-like peptide (GLP)-1 receptor agonists (GLP1 RA) injection, to a basal insulin is now recommended before the patient is advanced to MDI. This approach works very well in most patients since weight loss gives the patients an extra motivation to take medication regularly. Similarly, the patient does not require to take an insulin injection before each meal throughout the day in this approach.
Unfortunately, there are still a large number of patients with poor glycemic control who are still on MDI. Some of them were initiated on MDI before the availability of newer generations of medications. Some were started simply because the physician was not aware of or not the familiar with the new recommendations. Regardless of the reason, these patients are likely to remain on MDI despite chronic poor glycemic control since the physicians are understandably reluctant to step down the most advanced insulin therapy. In addition, there has been no data on the benefits and safety of the stepping-down approach from the most advanced insulin therapy to the more patient-friendly approach that is the combined use of oral SGLT2i and once-weekly GLP1 RA injection.
Detailed description
A prospective, randomized, open-label, controlled, parallel-group trial is planned. This study is an interdepartmental collaborative study among the Department of Internal Medicine, Department of Family \& Community Medicine (UCSF Fresno), Sierra Vista Family Medicine Residency Program and Division of Endocrinology.
The study will be conducted at the following multiple locations in order to maximize the patient recruitment:
- Internal medicine clinic at Derian Koligian ambulatory care center (ACC)
- Family practice medicine clinic at ACC
- Diabetes clinic at ACC
- Internal medicine clinic at University Medicine Associates in East medical Plaza
- Endocrine clinic at University Medicine Associates in East medical Plaza
- Sierra Vista clinics
The patients will be recruited during the first 12 months of the study or until the predetermined sample size is reached, whichever comes first.
The patient's primary care provider will be informed of the enrollment in the study if the participant gives the permission to do so.
All participants in both group will need to make all 3 visits to UCSF Clinical Research Center over 16- week period.
(1) First visit: Once the site co-investigators identify the suitable and interested study patient, a trained research coordinator will contact the patient for the first visit. The patient will be seen at the UCSF Clinical Research Center by the research coordinator and a physician co-investigator.
During the first visit, all patients in both group will
- be given the information about the study.
- sign the consent form.
- be randomly assigned to either treatment (i.e. Step Down) or control (MDI) group by using A Randomization Plan from http://www.randomization.com.
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ).
Medication changes at first visit:
In treatment group,
- All prandial insulin injections (Humalog, Novolog, Apidra, Novolin R or Humulin R), usually 3 times daily before meals, will be discontinued.
- Basal insulin (NPH, Lantus, Levimir, Toujeo or Tresiba), usually once daily at bed time, will be continued at 80 % of the home dose. The dose will be gradually increased until the patient is back on the home dose (the dose that the patient has been taking at home prior to the enrollment) or fasting BG of 80-130mg/dl is achieved by using the self-titration regimen.
- If the patient is on pre-mixed basal+prandial insulin 2-3 times daily, it will be discontinued and a basal insulin alone, (NPH, Lantus, Levemir, Toujeo or Tresiba), will be given at 40% of total daily dose of pre-mixed insulin. The dose will be gradually increased until fasting BG of 80-130mg/dl is achieved by using the self-titration regimen.
- Metformin, that most patients are expected to be on, will be continued, but other non-insulin oral medications for diabetes will be discontinued. If the patient is not on metformin, then Metformin ER will be started at 500mg with a meal for 2 weeks as a routine care and then 1000mg daily as a maintenance dose if tolerated.
- Both SGLT2i and GLP1 RA will be added to metformin and a basal insulin.
The patient will be trained on the injection technique of the once-weekly GLP1 RA, potential side effects, risk and benefits of all new medications in detail, hypoglycemia management and the self-titration regimen for the basal insulin.
In the control group, there will not be any change in MDI therapy, and the participants will continue to have the usual and standard care through the primary care provider. The participants should not receive SGLT2i and GLP1 RA during the study period.
(2) Second visit: At 4 weeks after the patient starts taking new medications, the patients will make the 2nd visit to the UCSF Clinical Research Center.
During the 2nd visit, the patient in the treatment group will
- be enquired about any side effect of the medications.
- be reviewed on insulin dose and the use of self-titration regimen for the basal insulin.
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ).
In the control group, there will not be any change in MDI therapy, and the participants will continue to have the usual and standard care through the primary care provider. The participants should not receive SGLT2i and GLP1 RA during the study period.
During the 2nd visit, the patient in the control group will
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ). (3) Third visit: The patients will make the 3rd or final visit to the UCSF Clinical Research Center at 12 weeks after 2nd visit or 16 weeks from the date of the start of both SGLT2i and a GLP1 RA.
During the 3rd visit, the patients in both groups will
- have the blood test for A1c, CMP, CBC, fasting lipid and measurements of body weight, height, blood pressure, and heart rate.
- complete both the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form and the Brief Medication Questionnaire (BMQ).
The investigators will try to make a clinic appointment with primary care provider one month prior to the last visit to the research center for those who are in the treatment group if the patient gives the permission to do so. Therefore the primary care provider will be able to order the medications through the patient's health insurance plan if the patient wishes to remain on the study medications beyond the study period. Alternatively, the patients can go back on insulin therapy that was given prior to the study.
Monitoring of the treatment group:
The patients in both groups will monitor FPGs daily at minimum. The research coordinator will call all participants in both groups at weeks 1, 2, 8, and 12 to review fasting glucose measurements, ask for possible adverse events, incidents of hypoglycemia, and any change in medication.
All participants in both groups in both groups will be reviewed again at the UCSF Clinical Research Center at weeks #4 and #16 for both blood tests and physical examinations.
Outcome measurements:
The primary outcome is the change in A1c at the end of 16 weeks of study period and secondary outcomes are the changes in fasting blood glucose, weight, blood pressure, heart rate, fasting lipids, serum sodium and potassium, serum creatinine, liver enzymes, CBC, medication adherence scores and treatment satisfaction scores . These changes will be compared between the two independent groups, namely the treatment group and the control group, and also within the same group.
Blood test and questionnaire:
The following blood work will be drawn and analyzed at the community regional medical center at baseline (first visit), at 4 weeks and at the end of the study at 16 weeks:
- A1c
- Complete Blood Count (CBC) with differential
- Complete metabolic panel (CMP)
- Fasting lipid profile
Patient satisfaction with treatment in both groups will be measured by the validated the Diabetes Medications Satisfaction (DM-SAT) Questionnaire form.
Patient adherence will be determined by using the Brief Medication Questionnaire (BMQ).
SAMPLE SIZE AND ANALYSIS PLAN:
The investigators will attempt to recruit and consent 20 patients in each arm that was calculated to provide an 80% statistical power at a 0.05 alpha in this continuous endpoint, two independent sample study.
The calculation was based on the following:
A mean Hemoglobin A1c of 8.5±1% at the initiation of the study period. In the treatment group we anticipate a decline in Hemoglobin A1c of 12-15% by the end of the study period. The standard deviation for the mean A1c was derived from the literature.
The data will be analyzed by using SPSS software. Significance testing will be conducted at the two-sided 5% level. Continuous variables will be examined for normality and if assumption is met, differences in mean values will be tested using Student's t test an analysis of variance (ANOVA). If not normally distributed, non-parametric procedures will be used, including Wilcoxan rank Sum test. Categorical data will be analyzed using Fisher's exact test and Chi square analysis. Since before/after comparisons will also be performed on the same study patients we will utilize paired t tests and McNemar's chi-square test.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Treatment group | Active comparator | Drug: GLP1 receptor agonist, Drug: basal insulin, Drug: SGLT2 inhibitor, Drug: MetforminInterventions: All prandial insulin injections, usually 3 times daily before meals, will be discontinued. Basal insulin, usually once daily at bed time, will be continued at 80 % of the home dose. Albiglutide OR Dulaglutide AND Empagliflozin will be added to metformin and a basal insulin. |
| Control group | No intervention | –Interventions: There will not be any change in insulin therapy, and they will continue to have the usual and standard care through the primary care provider. They should not receive SGLT2i and GLP1 RA during the study period. |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- The following patients with diabetes mellitus type 2 who can give written consent will be eligible for enrollment. They must meet all criteria.
- > 21 years of age
- Body mass index (BMI) ≥30 kg/m2
- On insulin at least 2 times daily comprising both a basal and a prandial insulin or a pre-mix insulin with or without other non-insulin medications for a least past 3 months
- A1c >8%
Key exclusion criteria (11 listed)
- The patients with any of the following criteria will be excluded.
- Any patient who does not meet the above inclusion criteria.
- Pregnancy
- Patients who are on a SGLT2i and a GLP1 RA injection at the time of enrollment.
- diabetes mellitus type 1
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 |
|---|---|---|
| GLP1 receptor agonistAlso: Albiglutide (Tanzeum) or , Dulaglutide (Trulicity)"Albiglutide or Dulaglutide" will be added to a basal insulin. | Drug | Treatment group |
| basal insulinAlso: Lantus, Toujeo, NPH, levemirThe participant will continue with the basal insulin. | Drug | Treatment group |
| SGLT2 inhibitorAlso: Empagliflozin (Jardiance)"Empagliflozin" will be added to a basal insulin. | Drug | Treatment group |
| MetforminThe participant will continue with metformin. | Drug | Treatment group |
Primary outcome
Change in A1c at the End of Study Period
Time frame: 16 weeks (from baseline to end of study at 16 weeks)
change in A1c (%) from baseline to end of study at 16 weeks
7 secondary outcomes
Changes in Weight
Time frame: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Blood Pressure
Time frame: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Heart Rate
Time frame: 16 weeks
Changes in LDL
Time frame: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Total Cholesterol
Time frame: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Serum Creatinine
Time frame: 16 weeks (from baseline to end of study at 16 weeks)
Changes in Treatment Satisfaction Scores (DM-SAT Total Score)
Time frame: 16 weeks (from baseline to end of study at 16 weeks)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Nov 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 27222560Herman WH, Kalyani RR, Wexler DJ, Matthews DR, Inzucchi SE. Response to Comment on American Diabetes Association. Approaches to Glycemic Treatment. Sec. 7. In Standards of Medical Care in Diabetes-2016. Diabetes Care 2016;39(Suppl. 1):S52-S59. Diabetes Care. 2016 Jun;39(6):e88-9. doi: 10.2337/dci16-0003. No abstract available.
- Background: PubMed 26731084Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, Dagogo-Jack S, DeFronzo RA, Einhorn D, Fonseca VA, Garber JR, Garvey WT, Grunberger G, Handelsman Y, Henry RR, Hirsch IB, Jellinger PS, McGill JB, Mechanick JI, Rosenblit PD, Umpierrez GE; American Association of Clinical Endocrinologists (AACE); American College of Endocrinology (ACE). CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. Endocr Pract. 2016 Jan;22(1):84-113. doi: 10.4158/EP151126.CS. No abstract available.
- Background: PubMed 25011946Diamant M, Nauck MA, Shaginian R, Malone JK, Cleall S, Reaney M, de Vries D, Hoogwerf BJ, MacConell L, Wolffenbuttel BH; 4B Study Group. Glucagon-like peptide 1 receptor agonist or bolus insulin with optimized basal insulin in type 2 diabetes. Diabetes Care. 2014 Oct;37(10):2763-73. doi: 10.2337/dc14-0876. Epub 2014 Jul 10.
- 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.
SOE NAING, MD principal investigator
UCSF - Fresno
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing GLP1 receptor agonist, basal insulin and SGLT2 inhibitor in people with Type 2 Diabetes Mellitus, run by University of California, San Francisco at 1 site in United States.
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 6 inclusion and 11 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: finished, as of the sponsor's last update on 10 Nov 2020. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Nov 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in A1c at the End of Study Period (time frame: 16 weeks (from baseline to end of study at 16 weeks)). 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 NCT02846233, which also lists 3 linked publications.
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 10 Nov 2020.