All subjects with type 1 diabetes need insulin and, given the current lack of disease-modifying drugs, all patients with type 2 diabetes will eventually need insulin if they live long lives. The data supporting the use of the new ‘ultra-long’ acting insulin analogue degludec which are currently being considered by the regulatory authorities show a continued improvement in duration and variability of action but the well-known downsides of weight-gain and hypoglycaemia (albeit diminished) remain.
So, what next for insulin? Previously an inhaled insulin was on the market and a number of similar insulins, with improved inhaler devices, were in development. The trial programmes largely came to a halt (and Pfizer’s Exubera insulin was withdrawn) following litigation in the US, which alleged that inhaled insulin could cause lung cancer. Nevertheless, some inhaled insulin development continues and this may well reach the market once again.
Oral insulins have an obvious attraction and various clever ways of avoiding gastric acid digestion of the insulin peptide have been devised. A major problem will be ensuring appropriate insulin delivery despite differing carbohydrate absorption according to the food being eaten. Perhaps the oral route will only be feasible for the basal insulin administration but this would clearly be an advance on current treatment.
‘Clever’ or ‘smart’ insulins, albeit still injected, may be a more achievable goal, at least in the short-to-medium term. This might mean insulins which predominantly work at the level of the liver (where endogenous insulin has its major role) or even insulins which are ‘glucose-dependent’. The latter group of insulin molecules would be activated in the setting of high glucose levels, but be inert when prevailing glycaemia was near-normal, thereby reducing the risks of hypoglycaemia.
In the short term, perhaps the most significant advance in insulin therapy is its use with GLP-1RA injectable agents. Data increasingly suggest that this co-administration reduces the risk of both hypoglycaeamia and weight-gain, hence making insulin treatment both safer and more effective….
Professor Steve Bain