Table 2.

Anti-hyperglycaemic agents in development

Agent	Mechanism of action	Advantages	Disadvantages
Sodium-dependent glucose transporters 2 inhibitors	Block renal glucose reabsorption in the proximal tubule	Possible natriuretic effect, action independent of insulin, little risk of hypoglycaemia	Glycosuria may increase the risk of genitourinary infections and exacerbate pro-fibrotic pathways, risk of dehydration
Glucokinase inhibitors	Activate glucokinase ‘glucose-sensors’ in both pancreatic and hepatic cells	Dual action on both liver and pancreas, weight neutral (possible reduction)	Safety (glucokinase expressed in neuronal cells), effect on kidney unknown
Glucagon antagonists	Blocks the antagonistic action of glucagon versus insulin	Glucagon integral to whole body glucose homeostasis	Awaiting further investigation
Bile acid sequestrants (cholestyramine, colestimide and colesevelam)	Unknown (possible pleiotropic effect of lipid lowering)	Beneficial effects on abnormal lipid profiles, safe in renal impairment	Gastrointestinal side effects very common, disruption of fat-soluble vitamin absorption
Amylin analogues	Synthetic analogue of beta-cell hormone amylin —delays gastric emptying, increases satiety and inhibits glucagon production	Weight neutral (possible reduction), safe in mild-to-moderate renal impairment	Subcutaneous administration, risk of hypoglycaemia, gastrointestinal side effects, not available outside USA