A clinical trial is currently recruiting eligible patients with type 2 diabetes to determine whether intermittent insulin therapy can preserve the functioning of the beta cells in the pancreas.
Individuals with type 2 diabetes either do not make enough insulin or their bodies do not properly respond to the insulin produced. Insulin, a hormone that helps the body control glucose levels in the blood, is produced and stored in beta cells of the pancreas. In type 2 diabetes, the beta cells of the pancreas cease to work properly and do not produce enough insulin, resulting in an increase in blood glucose levels.
While some individuals with type 2 diabetes can manage their blood glucose levels through diet and exercise, others require medications or insulin therapy. Insulin therapy aims to maintain levels of blood glucose within a specific range by injecting insulin into the body.
There are different insulin therapy regimens depending on the severity of the disease. Individuals generally start with a long-lasting shot of insulin before bedtime, but they may also take short-lasting shots of insulin immediately before or after meals. Apart from insulin injections, individuals may choose to use an insulin pump, which releases insulin into the body through a plastic tube under the abdomen. Taking multiple doses of insulin is an aggressive approach to treatment, called intensive insulin therapy.
Intermittent Insulin Therapy
Previous research studies have suggested that insulin injections for a few weeks may protect the beta cells in the body. This has allowed those with type 2 diabetes to maintain their blood sugar levels for several months without medication. However, this effect is only temporary.
A current clinical trial led by Canadian physicians Dr. Ravi Retnakaran and Dr. Bernard Zinman at Mount Sinai Hospital in Toronto, Ontario is now studying how to maintain this remission and potentially modify the “natural history of type 2 diabetes”. The clinical trial, called RESET IT, is specifically investigating whether intermittent insulin therapy can preserve the functioning of beta cells in the pancreas in early cases of type 2 diabetes.
This phase III, randomized controlled trial will group patients into one of two groups at random:
- Metformin alone
- Metformin + Intermittent Insulin Therapy
Metformin is generally the first medication prescribed for type 2 diabetes and works by improving the body’s sensitivity to insulin so that the body can use insulin more effectively. It also lowers the liver’s production of glucose.
The group taking metformin alone will first undergo intensive insulin therapy for three weeks. They will then be treated with metformin at 500 mg a day for the first two weeks and then 1000 mg twice a day for the duration of the trial, which is 24 months.
The group undergoing both metformin and intermittent insulin therapy will also start with a three-week course of intensive insulin therapy. After this, the patients will be treated with metformin at 500 mg twice a day for the first two weeks before progressing to 1000 mg twice a day for the duration of the trial. However, the participants will also be required to stop taking metformin for two weeks every three months. During this time, they will receive intermittent intensive insulin therapy for two weeks. The two-week course of insulin therapy will be repeated at 3, 6, 9, 12, 15, 18, and 21 months, with the final outcome measurement performed at 24 months.
The primary outcome of the study is beta cell function, which they will measure using the Insulin Secretion-Sensitivity Index-2 (ISSI-2). The secondary outcome is glycemic control, which will be assessed by glycated hemoglobin in the blood. Other outcome measurements include achievement of target glycemic control, achievement of glucose tolerance in the non-diabetic range, achievement of normal glucose tolerance, and insulin sensitivity.
This study, sponsored by Mount Sinai Hospital in Toronto, Canada, is looking to enroll 148 eligible participants. They expect to complete the study by September 2020.
Written by Jessica Gelar, HBSc
(1) “Early Intermittent Intensive Insulin Therapy As An Effective Treatment Of Type 2 Diabetes (RESET-IT Main Trial) – Full Text View – Clinicaltrials.Gov.” Clinicaltrials.Gov, 2018, https://clinicaltrials.gov/ct2/show/NCT02192424?term=type+2+diabetes&recrs=ab&cntry=CA&draw=2&rank=2.
(2) “Research Studies — Mount Sinai Hospital – Toronto.” Mount Sinai Hospital, 2018, http://www.mountsinai.on.ca/care/lscd/research-studies/clinical-trials.
(3) “Living With Type 2 Diabetes.” Canadian Diabetes Association, 2018, http://www.diabetes.ca/diabetes-and-you/living-with-type-2-diabetes.
(4) “My Site – Appendix 3: Examples Of Insulin Initiation And Titration Regimens In People With Type 2 Diabetes.” Guidelines.Diabetes.Ca, 2018, http://guidelines.diabetes.ca/browse/appendices/appendix3.
(5) “Type 2 Diabetes – Diagnosis And Treatment – Mayo Clinic.” Mayoclinic.Org, 2018, https://www.mayoclinic.org/diseases-conditions/type-2-diabetes/diagnosis-treatment/drc-20351199.