Effects of SGLT2 inhibitor on glucose flux, lipolysis and ketogenesis during insulin withdrawal in people with absolute or relative insulin deficiency
Dr Roselle Herring will find out if the Type 2 diabetes drugs ‘gliflozins’ are safe to use and can help to control blood glucose levels in people with Type 1 diabetes and people who produce less of their own insulin due to problems with their pancreas.
Background to research
In people without diabetes, the kidney plays an important role in preventing too much glucose from leaving the body, by reabsorbing it back into the bloodstream. Drugs called SGLT2 inhibitors or 'gliflozins' are used to treat Type 2 diabetes, as they prevent the kidneys from reabsorbing glucose, allowing it to be lost in urine. Phase 3 clinical trials of these drugs are also being carried out in people with Type 1 diabetes, to be used alongside insulin therapy. So far, they suggest that gliflozins prevent glucose levels from rising during periods of insulin deficiency. This helps to improve glucose control and reduce the risk of hypos, and also helps people to lose weight. However, the use of gliflozins in people with Type 1 diabetes also increases the risk of ketoacidosis, a dangerous condition that occurs when fats and proteins are broken down to produce energy. It is difficult to be aware of ketoacidosis, because the only sign is the rise in ketone levels (which make the blood more acidic). Therefore, gliflozins must be used in people with Type 1 diabetes with caution.
Dr Roselle Herring will carry out a study, aiming to understand how gliflozins help to control blood glucose levels in people with Type 1 diabetes (who produce none of their own insulin), and in people who produce less of their own insulin due to chronic pancreatitis or pancreatic surgery. Specifically, her team will look at the impact gliflozins have on glucose levels, fat breakdown and ketone production when insulin levels fall and glucose levels are high. Those who take part will receive either a gliflozin drug or a placebo (dummy drug). Glucose production and uptake, signs of ketoacidosis and urine glucose levels will be monitored before and during insulin being witheld. Safety is paramount, and the study will end if there are any signs of ketoacidosis or high blood glucose levels.
Potential benefit to people with diabetes
This research will help us find out if gliflozins are safe to use in people with Type 1 diabetes or people who produce less of their own insulin due to problems with their pancreas. It will improve our understanding of how gliflozins work when blood glucose levels are high and reveal whether the risk of ketoacidosis outweighs the benefits of improved glucose control, reduce hypos and weight loss.