oral hypoglycaemic agents
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These agents are only used when dietary treatment alone has failed *
Types of oral hypoglycaemic agents include:
- sulphonylureas which work by increasing beta cell sensitivity to glucose
thus increasing insulin release at a given plasma glucose concentration. This
leads directly to a reduction in hepatic glucose production and indirectly,
via a lowering of plasma glucose concentration, to decreased peripheral insulin
resistance
- biguanides e.g. metformin - which work by reducing hepatic glucose production.
There are also a number of other effects reported including stimulation of
peripheral glucose uptake, enhancement of insulin receptor binding and reduction
of glucose absorption from the intestine. These are less important mechanisms
of action
- glitazones - this is a class of drugs which reverse the insulin resistance
seen in type 2 diabetes. There is currently one licensed drug in this class,
pioglitazone. The effect of the thiazolidinediones is mediated by the activation
of a transcription regulator called peroxisome proliferator-activated receptor
gamma (PPAR-gamma). This action modulates adipogenesis and carbohydrate metabolism
in adipocytes and skeletal muscle. The only drug in this class in the UK is
pioglitazone
- alpha-glucosidase inhibitors e.g. acarbose - reversibly antagonise and
slow the action of sucrase, glucoamylase, dextrinase, maltase and isomaltase
enzymes within the intestinal tract. This hinders the production of absorbable
monosaccharidases and so reduces the postprandial blood glucose concentration
- meglitinides e.g repaglinide, nateglinide - lower blood glucose by stimulation
of insulin release from the pancreas
- gliptins e.g. sitagliptin, linagliptin - work via slowing degradation incretin
hormones**
- SGLT 2 inhibitors - a sodium-glucose cotransporter-2 (SGLT-2) inhibitor
that blocks the reabsorption of glucose in the kidneys and promotes excretion
of excess glucose in the urine (examples of this class include dapagliflozin,
canagliflozin, empagliflozin)
- oral semaglutide - an oral once daily GLP-1 analogue is available as a treatment option in type 2 diabetes
Note that in type 1 / insulin-dependent diabetes the essential therapy is insulin. Some oral hypoglycemic agents, such as metformin, may be used in addition in the management of patients with Type 1 diabetes.
Notes:
- * Latent Autoimmune Diabetes of Adulthood (LADA) may initially present as presumed type 2 diabetes
- is an example of a ketosis-prone diabetes and these patients may require early initiation of insulin therapy (rather than oral hypoglycaemic agents) as the pathological process relating to development of diabetes is insulin deficiency rather than insulin resistance
- ** incretin hormones - for example glucagon-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 (GLP-1) - these hormones are secreted by specialised enteroendocrine cells in response to a meal. The incretin hormones promote insulin secretion and inhibit glucagon secretion when blood glucose is high; when blood glucose is low then insulin secretion is inhibited and glucagon secretion is promoted
Last edited 03/2021 and last reviewed 03/2021
Links:
- sulphonylureas
- biguanides
- alpha-glucosidase inhibitors
- repaglinide and nateglinide ( meglitinides )
- thiazolidinediones
- NICE guidance - glitazone therapy in clinical practice
- oral hypoglycaemic agents and pregnancy
- type 2 diabetes mellitus
- NICE guidance - metformin in type 2 diabetes
- NICE guidance - sulfonylurea in type 2 diabetes
- NICE guidance - glitazone therapy in clinical practice
- dapagliflozin
- NICE guidance - dapagliflozin in combination therapy for treating type 2 diabetes
- NICE guidance - empagliflozin in combination therapy for treating type 2 diabetes
- latent autoimmune diabetes of adults (LADA)