DPP4inhibitors in Type 1 Diabetes
Condition: Type 1 Diabetes; Hypoglycaemia
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Hypoglycemia
Study type: Interventional
Phase: Phase 3

Summary: 
      A small, pilot, randomised, cross over trial that investigates the potential for DPPIVi
      therapy to reduce insulin requirements in type 1 diabetes was studied. We investigated
      whether this drug reduces daily insulin doses, leads to weight reduction, reduces blood
      glucose fluctuation and improves glucose control. Through reduction of blood glucose
      variability, we want investigated, whether it has the capability of improving the magnitude
      of epinephrine responses at 2.5mmol/L by performing a hyperinsulinaemic, hypoglycaemia clamp
      study after each arm. A successful outcome would then lead to an application for funds for a
      larger, multicentre intervention study. The benefits of this therapeutic advance are clear
      and this has the potential to make a dramatic improvement to the lives of people with type 1
      diabetes in our community.
    

Detailed description: 
      Ninety years ago the discovery of insulin and its development as a drug revolutionized the
      management of type 1 diabetes, which until that point had almost inevitably proven fatal.
      However, very rapidly it was recognized that like all "wonder" drugs there were problems with
      insulin. Elliot Joslin, one of the pioneers of diabetes therapy described insulin as "…a
      potent preparation alike for evil and for good"(1922). There are two major reasons for this.
      Firstly, in non-diabetic individuals insulin produced by the pancreas acts directly on the
      liver, the major organ for regulating blood glucose levels. In contrast, people with type 1
      diabetes inject insulin under the skin, and this is then absorbed into the circulation and
      much of it is degraded (~50%) before it gets to the liver. This means that in order to act
      effectively in the liver a type 1 diabetic needs to inject at least double the amount of
      insulin. Many studies have now shown that high insulin levels lead to weight gain,
      accelerated blood vessel disease (atherosclerosis) and a higher risk of suffering low blood
      glucose (hypoglycaemia). A second major problem is that individuals with type 1 show high
      levels of the hormone, glucagon. Glucagon is also produced in the pancreas and is normally
      regulated by pancreatic insulin, so the loss of this effect in people with type 1 diabetes
      means they run high glucagon levels. This has been shown to increase blood glucose,
      particularly after a meal. It is because of this that the diabetes community has called for
      novel therapies that can reduce high insulin levels and high glucagon levels. A new class of
      drugs called dipeptidylpeptidase IV inhibitors (DPPIVi) are currently used to treat people
      with type 2 diabetes. DPPIV inhibition increases endogenous levels of glucagon like peptide-1
      (GLP-1). These drugs have a number of actions but the most relevant to this application is
      that they directly suppress glucagon, induce satiety (i.e. reduce hunger and leads to a
      reduction in body weight) and indirectly reduce the need for high dose insulin injections.
      This makes them an ideal candidate drug as an insulin sparing or adjunct therapy in type 1
      diabetes, but there is very limited data to date for this use.
    

Intervention name(s): Saxagliptin
Intervention type(s): Drug
Intervention description(s): 5mg saxagliptin
Intervention MeSH terms: Saxagliptin
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: crossover trial between Saxaglipin and Placebo with 2 week washout in between
Masking: Double (Participant, Investigator)
Primary purpose: Prevention