Clinical trial NCT03670641
Conditions: Type 2 Diabetes Mellitus
Keywords: Insulin therapy Continuous glucose monitor
Sponsor: Sandra Sobel
Start date: 2019-03-26; Completion date: 2020-07-31
Enrollment: 10 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
REMIT-DM is a feasibility pilot study where participants will be recruited soon after their diagnosis of type 2 diabetes to be placed immediately on insulin therapy for maximum of four weeks with titrations of insulin guided by glucose levels and trends provided by a continuous glucose monitor (CGM), with the purpose of achieving diabetes remission.

Detailed description:
REMIT-DM is a feasibility pilot study that aims to show that previously published diabetes remission through early use and titration of short-term insulin therapy is possible and safe in the ambulatory diverse American population of patients with T2D, with continuous glucose level and trend information provided by CGM. We developed the algorithm based on published diabetes remission studies and include within the algorithm the CGM trend arrows to further refine insulin doses for both safety and efficacy purposes. Data captured by the CGM transmits automatically to the cloud and is accessible at any time of day by the multidisciplinary diabetes team, which includes the certified diabetes educator (CDE) and Endocrinologist. The CGM-guided insulin titration algorithm is designed to achieve euglycemia (defined as fasting CBG \< 100 mg/dL, and 2 hour post-prandial CBG \< 120 mg/dL) within 2 weeks of initiating insulin therapy, then to help maintain euglycemia for 2 weeks before discontinuing insulin entirely. Ten participants will undergo a maximum of 4 weeks of insulin therapy and will be assessed for remission afterwards to confirm enough recovery of beta cell function. (Complete remission is defined as fasting glycemia \<100 mg/dL without use of pharmacological therapy.) Afterwards, we will implement American Diabetes Association (ADA) guidelines for standard glycemic management, as necessary. We will use the data collected during this feasibility study to sharpen the CGM-guided insulin titration algorithm for creation of a T2DM remission mobile application that could then be tested and studied in a larger sample size.

The feasibility study will also take into account clinically meaningful data points e.g. the number of phone calls between the patient and the diabetes team, the patient experience, and patient satisfaction.

Arms: arm 1: 10 individuals with newly diagnosed type 2 diabetes will be started on basal (glargine) bolus (lispro) insulin therapy for up to 4 weeks with titrations guided by continuous glucose monitor (Dexcom G6) to achieve euglycemia and then insulin stopped after 4 weeks with hopes of diabetes remission.
Interventions: intervention 1: Glargine intervention 2: Lispro intervention 3: Dexcom G6
Intervention descriptions: intervention 1: Dexcom G6 CGM will be used to guide daily insulin glargine and lispro dose titrations in participants with newly diagnosed type 2 diabetes. After 4 weeks of CGM and insulin therapy, insulin will be discontinued and participant's labs monitored every 3 months to determine if diabetes remission achieved. intervention 2: Dexcom G6 CGM will be used to guide daily insulin glargine and lispro dose titrations in participants with newly diagnosed type 2 diabetes. After 4 weeks of CGM and insulin therapy, insulin will be discontinued and participant's labs monitored every 3 months to determine if diabetes remission achieved. intervention 3: Dexcom G6 CGM will be used to guide daily insulin glargine and lispro dose titrations in participants with newly diagnosed type 2 diabetes. After 4 weeks of CGM and insulin therapy, insulin will be discontinued and participant's labs monitored every 3 months to determine if diabetes remission achieved.

Protocol documents:
Prot_SAP_000.pdf: 
Page 1 of 5 
 
Study Protocol  
 
 
 
 
 
 
Official Title: Remission through Early Monitored Insulin Therapy 
- Duration Month (REMIT-DM) 
  
 
 
ClinicalTrials.gov ID (NCT number): NCT03670641 
 
 
 
Protocol Date: 06 July 2021 
 
 
 
 


Page 2 of 5 
 
Scientific Background 
 
REMIT-DM is a feasibility study that aims to show that previously 
published diabetes remission through early use and titration of short-
term insulin therapy is possible and safe in the ambulatory diverse 
American population of patients with T2D, with continuous glucose 
level and trend information provided by CGM. We developed the 
algorithm based on published diabetes remission studies and include 
within the algorithm the CGM trend arrows to further refine insulin 
doses for both safety and efficacy purposes. Data captured by the CGM 
transmits automatically to the cloud and is accessible at any time of day 
by the multidisciplinary diabetes team, which includes the certified 
diabetes educator (CDE) and Endocrinologist. The CGM-guided insulin 
titration algorithm is designed to achieve euglycemia (defined as fasting 
CBG < 100 mg/dL, and 2 hour post-prandial CBG < 120 mg/dL) within 
2 weeks of initiating insulin therapy, then to help maintain euglycemia 
for 2 weeks before discontinuing insulin entirely. Ten subjects will 
undergo a maximum of 4 weeks of insulin therapy and will be assessed 
for remission afterwards to confirm enough recovery of beta cell 
function. (Complete remission is defined as fasting glycemia <100 
mg/dL without use of pharmacological therapy.) Afterwards, we will 
implement American Diabetes Association (ADA) guidelines for 
standard glycemic management, as necessary. We will use the data 
collected during this feasibility study to sharpen the CGM-guided insulin 
titration algorithm for creation of a T2DM remission mobile application 
that could then be tested and studied in a larger sample size. 
The feasibility study will also take into account clinically meaningful 
data points e.g. the number of phone calls between the patient and the 
diabetes team, the patient experience, and patient satisfaction. 
Study Objectives 
 
 
 


Page 3 of 5 
 
Study Design & Methods 
 
Participants will be assessed by the endocrinologist and diabetes 
educator to be able to perform skills necessary for CGM use and insulin 
delivery. If the CDE determines that the patient is unable or unwilling to 
perform the necessary care tasks, this will be communicated to the 
endocrinologist for potential exclusion from the study. 
 
The Research Activities: 
 
-Study Visit 1: The PAID-5 survey will be administered to assess 
diabetes distress by the RN CDE prior to the diabetes education session. 
Subject will undergo standard of care diabetes self-management 
education by the study team members, including the initiation of the 
CGM. OGTT lab blood draw will be done. 
 
-Study Visit 2: Subject will undergo standard of care education for 
insulin start. Research activity: study team will provide the insulins and 
instruct the subject in the insulin titration protocol and how CGM 
readings will be used to manage insulin doses. Subject will adjust their 
meal-time insulin doses by the before meal blood sugar and the CGM 
predictive arrows and their daily basal insulin based on how close 
fasting glucose was to glucose target. Study team will confirm that 
subject understands how the study works using the teach-back method. 
Ample time for question and answer will be allotted. 
 
-Study Visit 3: The PAID-5 will be administered at this visit as well as 
the satisfaction survey. These will both be administered by the RN CDE 
prior to the education session. If remission is achieved, patient will turn 
in their CGM and go off their insulin. A repeat OGTT lab blood draw 
will be done at this time as well. If remission is not achieved, the 
standard ADA algorithm would apply and patient would be placed back 
on their medication(s). However, there may be some patients that would 
prefer to stay on insulin or for which remaining on insulin therapy is 


Page 4 of 5 
 
appropriate. The patient will be started on appropriate therapy as guided 
by clinical decision making. 
 
-Study Visits 4-6: post 4 weeks-1 year patient will have standard of care 
endocrinology visits driven by clinical decision making. 
 
-Study Visit 7: At 12 months, the PAID-5 and satisfaction survey will 
again be administered by the RN CDE. 
 
Algorithm Development/Data Analysis Period: 
 
-Post 12 month intervention period: Algorithm and Protocol 
development 
 
All program data, e.g. number of calls, length of calls, information 
reviewed/requested on call, documentation of extraneous calls, e.g. after 
hours/outside of schedule. Clinical outcomes, e.g. rates of 
hypoglycemia, laboratory results will be analyzed and reviewed. Based 
on the findings a full protocol that includes the finalized insulin titration 
algorithm and program processes will be prepared. 
 
Eligibility Criteria 
 
Inclusion criteria: 
• Age ≥18 
• A1C criteria - >7.0 
• Diagnosed with T2D within 4 years 
• Lifestyle controlled 
• Subject may be on up to 2 medications for diabetes. 
• Smart phone or home computer compatible with DEXCOM 
CLARITY software 
• English speaking 
• Assessed by endocrinologist and diabetes educator to be able to 
perform skills necessary for CGM use and insulin delivery 


Page 5 of 5 
 
 
Exclusion criteria: 
• Autoimmune Type 1 DM, defined as positive GAD65 or islet cell 
antibodies 
• Pregnant 
• Chronic Kidney Disease (CKD) Stage IV or greater 
• Mental and/or cognitive disorder (based on documented disorder 
and/or assessment of physician or educator) 
• No access to computer for downloading CGM 
• BMI <18.0 
 
Statistical Considerations 
 
This is a feasibility study that does not require power calculation. 
 
Baseline characteristics will be described using measures of central 
tendencies (means, median, standard deviations). To examine time to 
glucose target range, hypo/and hyperglycemia, logistic regression will 
be used. Covariates in the models will include demographic factors, 
glucose dosing information, insulin protocol used. 

ICF_001.pdf: 
Page 1 of 1 
 
Study Consent  
 
 
 
 
 
 
Official Title: Remission through Early Monitored Insulin Therapy 
- Duration Month (REMIT-DM) 
  
 
 
ClinicalTrials.gov ID (NCT number): NCT03670641 
 
 
 
Consent Date: 06 July 2021 
 
 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
1
Division of Endocrinology and Metabolism
Consent to Act as a Participant in a Research Study
Study Title:
Remission through Early Monitored Insulin Therapy Duration-Month (REMIT-DM)
Principal Investigator:
Sandra Indacochea Sobel, MD
Clinical Assistant Professor of Medicine,
Division of Endocrinology and Metabolism
Clinical Chief of Endocrinology, UPMC Mercy
1400 Locust Street Suite 5120 Pittsburgh, PA 15217
T:  412-232-9150 sobelsi@upmc.edu
Source of Support: Pitt Innovation Challenge (PInCH) 2017, Clinical and Translational 
Science Institute (CTSI)
What is the purpose of this study? 
The purpose of this study is to see if use of continuous glucose monitoring data 
from people diagnosed with type 2 diabetes within the past 4 years and started on 
insulin temporarily can guide an insulin dosing system, called an algorithm, with the 
hopes of achieving diabetes remission after the short-term use of insulin. We also want 
to find out about experiences of patients using a CGM device in this way.
Why is this research being done? 
Type 2 diabetes is a disease where the pancreas does not make enough insulin and/or 
the insulin doesn’t work as it should. Many people with type 2 diabetes will use insulin to 
control their blood sugars, often after they have had the disease for a while.
However, there have been studies showing that giving insulin early on for a very short 
period can rest the insulin-making cells in the body. In many cases, it can make it so 
that people who recently found out that they have type 2 diabetes can have normal 
blood sugars without needing medication for a year or more. This is called diabetes 
remission. 
Studies about this, so far, have taken place with people admitted to the hospital for 
several weeks. While in the hospital, blood sugar finger stick tests are done so that 
doctors can adjust insulin doses. This study will use this method by giving insulin within 
4 years of a diabetes diagnosis, to cause a remission without having the person stay in 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
2
the hospital and without frequent finger sticks. This study will be done in the outpatient 
setting. 
This study will use newer blood sugar testing technology that is available to people with 
diabetes. It can give blood sugar readings every few minutes with minimal finger pricks. 
(You may have to prick your finger if there is inconsistency between your blood sugar 
reading and your symptoms.) This technology is called Continuous Glucose Monitoring, 
or CGM for short. CGM is already tested and available. The CGM device has 3 parts: a 
catheter, a small sensor that is placed on your stomach and a pager-like device that 
gives you your blood sugar readings.
Many of our patients are already using CGM to measure their blood sugars instead of 
doing finger pricks. Instead of admitting people to the hospital to achieve a “remission” 
with frequent finger pricks to gauge insulin doses, we want to use CGM to measure 
blood sugars as an outpatient. This allows for less finger pricks and many more blood 
sugar values to help guide better insulin adjusting. We will show you how to use your 
CGM and we will give you a lot of education and support to ensure your safety and well-
being during this study. 
Who is being asked to take part in this research study?
You are invited to be part of this study as you have been diagnosed with type 2 diabetes 
in the last 4 years as diagnosed by your endocrinologist or primary care provider. We 
plan to invite 10 people with type 2 diabetes to participate. You are a good fit for this 
study because you have type 2 diabetes, a hemoglobin A1C level >7.0% (a measure of 
blood sugars over a 3-month period), are over the age of 18 years old, and have access 
to a home computer (desktop or laptop for downloading CGM records). 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
3
What procedures will be performed for research purposes?
If you decide to take part in this research study, you will have the following procedures 
that are not part of your standard medical care: 
1. You will be asked to sign a consent form agreeing to participate in this study 
2. You will be prescribed insulin therapy from the beginning for up to 4 weeks to try 
and achieve diabetes remission. If you are already on metformin therapy, you 
may continue this medication but will be asked to hold it for 2 days twice during 
the study to perform standard blood tests, which includes an oral glucose 
tolerance test (OGTT) performed at the first and third study visit.
3. You will be asked to use the readings from a CGM so that your insulin doses can 
be adjusted daily to achieve diabetes remission. You will have access to a team 
of experienced diabetes educators who will guide you during this process under 
the direction of our endocrinologists Dr. Sobel and Dr. Rometo.
4. You will be asked to complete surveys about:
a. your satisfaction with the study
b. your experience now living with diabetes 
The surveys will be done when you are having your initial, 3 month and at the 
final study visit. 
5. Your Private Health Information in your Electronic Medical Record will be 
accessed by our team. Members of the research team including the diabetes 
educators, physicians, statistician and/or study coordinator will access your 
record for up to 24 months after the study is complete to obtain lab values, data, 
and changes in condition or medical care.
6.  After you have returned the CGM at one month, we will collect all of your CGM 
data from the Dexcom CLARITY software as well as medical record data from 
your routine diabetes care team visits. There are no procedures you will be 
asked to do. We will collect all the data from all of the participants and analyze it 
to see if the use of CGM and algorithm were effective in getting patients to 
normal blood sugars.
We will provide you with standard diabetes clinical procedures and education that are 
considered usual care. These are not research procedures. If you are a patient in our 
clinic not in a study, your care includes:

Visits with your endocrinologist which include an initial visit and follow-up visits at 
3 months, 6 months, 9 months, and 12 months. 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
4

The visit with the endocrinologist will include a full assessment that includes a 
physical exam and review. Your endocrinologist will also order routine diabetes 
labs for these visits. 

You will also be asked to wear a Continuous Glucose Monitor (CGM) to 
determine the right insulin doses for you. 

You will also visit with a diabetes educator and dietitian who will provide 
instruction on healthy eating, activity, care of high and low blood sugars, CGM 
use and information on who and when to call the Diabetes Team. 
As part of your standard medical care, you will be asked to come in 4-6 weeks after you 
start the insulin for a visit with the endocrinologist who will review your test results and 
see if you have rested your insulin-making cells for diabetes remission. If further 
medicines should be needed to help control your blood sugars after the short-term use 
of insulin, then the endocrinologist will follow the current standard of diabetes 
management according to the American Diabetes Association guidelines in prescribing 
your therapy. After that, the follow-up portion of the study will last 12 months and most 
data collection will take place as part of the routine visits with the endocrinologist. You 
will have a visit with the diabetes educator and endocrinologist at 12 months.
Your participation in this study will not change your standard medical care nor eliminate 
the need for medical visits as per your doctor’s order. 
What are the possible risks, side effects, and discomforts of this research study?
1. There is a risk of a breach of confidentiality if your medical information or your 
identity are obtained by someone other than the investigators, but precautions 
will be taken to prevent this from happening.
2. We also cannot guarantee that your diabetes responds to the use of insulin and 
achieves remission.
3. Risks of insulin use include low blood sugar, weight gain, allergic reactions and 
infections, and drug interactions. Symptoms of low blood sugar include 
headache, hunger, weakness, sweating, tremors, irritability, trouble 
concentrating, rapid breathing, fast heartbeat, fainting, or seizure (severe 
hypoglycemia can be fatal). 
4. Risks of CGM use include mild pain at time of insertion of subcutaneous 
catheter, minor bleeding or bruising at insertion site, skin irritation around 
insertion site, infection or lipohypertrophy. 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
5
Are there any possible benefits from taking part in this study?
There is no guarantee that you will benefit from being in this research, however this 
study may contribute to diabetes care knowledge for all. 
What treatments or procedures are available if I decide not to take part in this 
research study?
If you choose not to participate you will still see your endocrinologist as usual and you 
can still see the diabetes educator and registered dietitian. You can also utilize a 
professional continuous glucose monitor for 2 weeks as part of routine care. 
If I agree to take part in this research study, will I be told of any new risks that 
may be found during the study? 
You will be promptly notified if any new information either good or bad about type 2 
diabetes intensive insulin therapy for remission develops during this study and which 
may cause you to change your mind about continuing to participate. 
Will my insurance provider or I be charged for the costs of any procedures 
performed as part of this research study?
Neither you nor your insurance provider will be charged for the costs of any of the 
procedures performed for this research study. You will be charged in the usual manner 
for your standard medical care (care you would receive even if you were not 
participating in this research study).
Will I be paid if I take part in this study?  
Yes, you will be paid $250 for participating. You will receive this stipend at clinic visits 1, 
3, 4, 6 and 7 where we obtain information for use in our study. You will receive $50 at 
each of these visits. You will be paid on a reloadable debit card. We are also paying for 
your parking. 
Since you are being compensated for your participation in this study, your name, 
address, and social security number will be released to the Accounting Office. If the 
total reimbursement for your participation in research is greater than $600 in a year, this 
will be reported to the Internal Revenue Service (IRS) as income. 
The insulin and CGM are being paid for through a $25,000 PINCH award and the blood 
glucose testing supplies are being donated by the UPMC Center for Diabetes and 
Endocrinology. 
Who will pay if I am injured because of taking part in this study?
You waive no legal rights from signing this consent form. Emergency medical treatment 
for injuries directly related to your participation in this research study will be provided to 
you by the hospitals of UPMC. Your insurance company may be billed for the costs of 
this emergency treatment, but none of these costs will be charged directly to you. If your 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
6
research-related injury requires medical care beyond this emergency treatment, you will 
be responsible for the costs of this follow-up care. At this time, there is no plan for any 
additional financial compensation.
If you believe that the research procedures have resulted in an injury to you: 
Immediately contact the Principal Investigator Sandra Sobel, MD. She is listed on the 
first page of this form.
How will my data be protected?
Any data produced from this study will be stored in your electronic health record and 
available to physicians and medical professionals that you see for care. Data from 
surveys or from the Dexcom CGM will be de-identified and assigned a subject ID if 
moved from a secure server. The research team will have access to your electronic 
health record. Every member of the research team is under a confidentiality agreement. 
Just as with the use of your information for health care purposes, we cannot guarantee 
its privacy. Your data, if printed and/or published, will be de-identified. Hard copies of 
research data will be de-identified and stored in locked file cabinets in the Division of 
Endocrinology and Metabolism for a minimum of 7 years. Any information related to 
adverse events you may suffer during the study period will be disclosed to your 
physician in your electronic medical record. 
Who will have access to identifiable information related to my participation in this 
research study?
The investigators listed on the first page of this consent form and their clinical staff (who 
help to provide your diabetes care, like the dietitian) may have access to identifiable 
information (which may include your identifiable medical information) related to your 
participation in this research study:
Authorized representatives of the University of Pittsburgh Research Conduct and 
Compliance Office. Their office is responsible for monitoring appropriate conduct of 
research studies on campus. 
Authorized representatives of the sponsor of this research study, the Clinical and 
Translational Science Institute (CTSI) on behalf of the Pitt Innovation Challenge (PInCh 
2017) award. 
In unusual cases, the investigators may be required to release identifiable information 
(which may include your identifiable health information) related to your participation in 
this research study in response to an order from a court of law. If the investigators learn 
that you or someone with whom you are involved with is in danger or potential harm, 
they will need to inform, as required by Pennsylvania law, the appropriate agencies. 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
7
Authorized representatives of the UPMC Health system hospitals or other affiliated 
health care providers may have access to identifiable information (which may include 
your identifiable medical information). The fact that you are participating in a research 
study and that you are undergoing certain research procedures (but not the results of 
these procedures) may also be made known to individuals involved in insurance billing 
and/or other administrative activities associated with conduct of the study. 
Your data from your blood sugar monitoring and medical record used in this research 
may contribute to a new discovery or treatment.  In some instances, these discoveries 
or treatments may be of commercial value and may be sold, patented, or licensed by 
the investigators and the University of Pittsburgh for use in other research or the 
development of new products.  You will not retain any property rights nor will you share 
in any money that the investigators, the University of Pittsburgh, or their agents may 
receive.
Is my participation in this study voluntary?
Your participation in this research study, to include the use and disclosure of your 
identifiable information for the purposes described above, is completely voluntary. 
(Note, however, that if you do not provide your consent for the use and disclosure of 
your identifiable health information for the purposes described above, you will not be 
allowed, in general, to participate in the research study.) Whether you provide your 
consent for participation in this research study will have no effect on your current or 
future medical care at a UPMC Health systems hospital or affiliated health care provider 
or your current or future relationship with a health insurance provider. 
May I withdraw, at a future date, my consent for participation in this research 
study?
At any time, you may withdraw your participation from REMIT DM: Remission through 
Early Monitored Insulin Therapy Duration-Month. You may withdraw by telling the team 
in writing that you are no longer interested in participating in the research study. You 
may do this by using the MyUPMC communication platform or by sending a letter in the 
mail. This letter must be signed and dated and should be sent to: 
Sandra Indacochea Sobel, MD
Clinical Assistant Professor of Medicine, Division of Endocrinology and Metabolism
Clinical Chief of Endocrinology, UPMC Mercy
1400 Locust Street Suite 5120 Pittsburgh, PA 15217
If you withdraw from the study, your de-identified research data, up until the time you 
withdrew, may still be published. Your participation is completely voluntary and your 
decision to participate, or to later withdraw from it, will not affect your current or future 
medical care at UPMC or your participation in the current research protocol. If you 
would like additional information, you may contact the study coordinator, Shari Reynolds 


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
8
at 412-383-0570. Questions about your rights as a research participant may be 
answered by the Human Subjects Protection Advocate at the University of Pittsburgh 
IRB Office 866-212-2668.
It is possible that you may be removed from the research study by the researchers if, for 
example, you are not able to keep up with the visits, calls, dosing instructions or if, for 
any reason you have to be admitted to the hospital during the one month of insulin 
therapy.
********************************************************************************************


University of Pittsburgh STUDY19070117    Effective: 7/6/2021    Expires: 7/5/2022
9
VOLUNTARY CONSENT 
All the above has been explained to me and all of my current questions have been 
answered. I understand that I am encouraged to ask questions about any aspect of this 
research study during this study, and that such future questions will be answered by the 
researchers listed on the first page of this form. 
Any questions that I have about my rights as a research participant will be answered by 
the Human Subject Protection Advocate of the IRB Office, University of Pittsburgh (1-
866-212-2668)
By signing this form, I agree to participate in this research study. A copy of this consent 
form will be given to me. 
______________________________________________________________________
Participant’s Signature
Date and time 
______________________________________________________________________
Participant’s Printed Name 
CERTIFICATION of INFORMED CONSENT
I certify that I have explained the nature and purpose of this research study to the 
above-named individual(s), and I have discussed the potential health benefits and 
possible risks of study participation. Any questions the individual(s) have about the 
study have been answered, and we will always be available to address future questions 
as they arise.
______________________________________________________________________
Printed Name of Person Obtaining Consent
Role in Research Study
______________________________________________________________________
Signature of Person Obtaining Consent
Date and time