Diabetes Medication
Drugs which reduce blood glucose
Insulins
These are versions of normal insulin which are given by subcutaneous injection.
– There are many different forms of insulin, which have different half-lives:
e.g. Insulin glulisine + insulin aspart + insulin lispro
These are rapidly acting [RAPID]
Regular Insulin
This is a recombinant form of human insulin.
– Must deliver to patients using an insulin syringe, as in normal syringe there are 100units/ml [REGULAR]
Neutral Protamine Hagedorn
This is intermediate acting. It is a suspension of insulin-zinc complexes with protamine which slows absorption [INTERMEDIATE]
Ultralente insulin + Detemir + Glargine
These are long acting. They have changes to the amino acid sequence which delays absorption [LONG]
Side effects
- Overdose can result in hypoglycemia
- Hypokalemia
- Weight gain
- Lipodystrophy (fat build up) at the injection site
Metformin
This reduces gluconeogenesis and increases peripheral insulin sensitivity.
– Also acts to decrease the intestinal absorption of glucose
– It does not depend of functioning ß-cells as it exerts most its effects at the liver
– Taken as a tablet and safe to use if breastfeeding
– Metformin is good in that it rarely causes hypoglycemia or weight gain on its own.
Side effects
- Lactic acidosis in renal failure patients due to decreased drug excretion or in liver failure patients
- GI upset –> if this occurs, switch to the modified release tablet
Sulphonylureas
These drugs bind to the SUR1 receptor on KATP channels on the beta-cells closing them, mainly increasing insulin release and also increasing tissue insulin sensitivity. These drugs are very useful in treating type II diabetes but are not effective against type 1 diabetes.
1st generation:
Tolbutamide
This is a short acting sulphonylurea
Chlorpropamide
Long acting which used in the treatment of Neurogenic diabetes insipidus as it potentiates ADH action at V2 receptors.
– However, it is long acting and has highest chance of hypoglycemia, produces SIADH and has disulfiram-like reactions with alcohol.
2nd generation:
Glipizide
This is an intermediate acting drug.
3rd generation:
Glimepiride
This is a long acting sulphonylurea
Side effects
- Hypoglycemia – proportional to how long the drug acts for
- Weight gain
- Not used in pregnancy as can cross the placenta
- Some can cause SIADH leading to hyponatreamia
- People develop tolerance due to downregulation of sulphonylurea receptors.
Meglitinides
e.g. Repaglinide
These drugs also block KATP channels causing an increase in insulin secretion.
– It is a very fast acting drug which is used to limit post-prandial hyperglycemia
– Also used in people with sulpha-drug allergies
Side effects
- Hypoglycaemia
- Weight Gain
Thiazolidinediones
e.g. Pioglitazone + Rosiglitazone (-glitazone)
These PPAR-y agonists increase tissue sensitivity to insulin and activate hormone adiponectin
– They also act on muscle and fat to increase glucose uptake and lipogenesis
– Therefore they reduce plasma glucose but do not cause hypoglycemia.
Side effects
- Exacerbate congestive heart failure due to fluid retention
- Osteoporosis
- Bladder Cancer
- Weight Gain
Alpha-glucosidase inhibitors
e.g. Acarbose + Miglitol
These inhibit amylase and glucoside enzymes which break down starch in the intestines
– Therefore, act to reduce the absorption of glucose into the bloodstream
Side effects
- Flatulence –> Not used in IBD or Liver cirrhosis
Incretins
e.g. Exenatide + Liraglutide
These are synthetic versions of GLP-1 which reduce appetite, taken by subcutaneous injection
– Acts by increasing insulin secretion, decreasing glucagon secretion and decreasing appetite
Side effects
- Sickness
- Pancreatitis
- Also cause weight loss
DPP-4 inhibitors
e.g. Sitagliptin, Saxagliptin (-gliptin)
-These inhibit the DPP-4 enzyme which breaks down the incretins GLP-1 and GIP
Side effects
- Indirectly cause sickness
- Pancreatitis
- Weight loss
Amylin analog
e.g. Pramlintide
This is a polypeptide stored and secreted by B-cells which acts with insulin to reduce blood sugar
– Treats type 1 and 2 diabetes by slowing gastric emptying and decreasing glucagon secretion.
SGLTI (selective sodium glucose transporter 2 inhibitor)
e.g. Empagliflozin (-gliflozin)
– Blocks glucose reabsorption in the kidneys to promote excretion of excess glucose in urine
Side effects
- Genital infections
- UTI due to increased glucose in urine
- Diabetic Ketoacidosis
Drugs which increase blood glucose
Glucagon
This is a hormone which is made by the alpha cells of the pancreas and is gluconeogenic
– It used to rescue people from hypoglycaemic crisis acting to increase the serum glucose concentration
– Has minimal side effects
Diazoxide
This is a potassium channel opener that binds and opens ATP-sensitive K+ channels in the ß-cells causing hyperpolarization –> inhibits insulin release.
– Used to treat hypoglycemia secondary to an insulinoma
– Also used as a potent vasodilator used in hypertensive emergency
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