Antidiabetic medications

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Group
Examples
Mechanism
Contrindications and side effects
Other notes
Biguinides
Metformin
Reduce hepatic glucose production
Increases insulin sensitivity
GI side effects are common
Risk of lactic acidosis in acute illness or reduced GFR. CI in those with impaired hepatic function and hx of ETOH excess due to increased lactic acidosis risk.

Sulfonylureas
Gliclazide
Glimepiride (long acting sulfonylurea)
Glimbenclamide
glipizide
Increases insulin secretion from pancreatic B cells through closing ATP-sensitive potassium channels.
Risk of hypoglycaemia
Weight gain

Meglitinides
Repaglinide
Nateglinide
Works the same way as sulfonylurea – but shorter acting.
Hypoglycaemia

Dipeptidyl peptidase IV inhibitors (DPP4)
Linagliptin
Sitagliptin
Saxagliptin
Alogliptin
Inhibit DPP-4 which breaks down incretins (GLP-1 and GIP) therefore increases effect of endogenous incretins. (see GLP-1)

Does not affect weight
Does not cause hypoglycaemia like sulfonylureas.
Thiazolindenediones
Pioglitazone
Binds and activates peroxisome proliferator activated recptor –y (PPAR-y) in the nucleous of adipose tissues which causes expression of genes involved in metabolism leading to increased effectiveness of endogenous insulin.
Can cause weight gain
Rosiglitazone increases risk of MIs. Pioglitazone can worsen CCF and cause fluid retention and is therefore CI. Increased risk of bone fractures. Possible increased risk of bladder cancer.
Does not cause hypoglycaemia
Can reduce fatty liver/NASH
Potentiates insulin therefore very effective when combined with insulin but this may increase risk of fluid retention.
Glucagon-like peptide 1 (GLP 1) mimetics
Exenatide
Dulaglutide
Liraglutide
Bydureon (long acting exenatide)
Mimics incretins from the intestines – causes increased insulin secretion when blood glucose levels are high.  Reduces glucagon release with hyperglycaemia, reduces gastric emptying and reduces appetite.
May cause GI symptoms+ local irritation.
Increased risk of pancreatitis.
Consider reducing sulfonylurea if used together as GLP1 agonists can increase risk of hypoglycaemia.
Can promote weight loss.
Can increase weight loss and does not cause hypoglycaemia on its own.
NICE suggests trial of GLP-1 if triple therapy have failed and:
BMI greater than 35 and weight loss would be beneficial, or BMI less than 35 but significant occupational implications to insulin use or significant benefits of weight loss given other comorbidities. Only continue GLP-1 agonists if reduction in HbA1C of more than 11 mmol (1%) and weight loss of 3% from baseline. 
a-glucosidase inhibitors
Acarbose
Miglitol
Inhibit disaccharidases in gut slowing carbohydrate absorption in gut
Bloating, flatulence and diarrhea – often not acceptable to patients.

Sodium glucose cotransporter 2 inhibitors (SGLT2)
Empagliflozine
Dapagliflozine
Blocks glucose reabsorption in the kidneys causing glucosuria.
Increased frequency of urinary tract infections/genital infections
Risk of ketoacidosis
Can promote weight loss.

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References: 
1)Walker BR, Colledge NR, Ralston SH, Penman ID (Eds), Davidson's principles and practice of medicine, 22nd ed., Edinburgh, Churchill Livingstone, 2014
2)https://www.diabete.qc.ca/en/understand-diabetes/all-about-diabetes/getdocument/tableau-medication
3) http://www.gpnotebook.co.uk/simplepage.cfm?ID=x20080605153841672570
4) https://www.drugbank.ca/drugs/DB01276
5) https://www.medicines.org.uk/emc/medicine/24665 

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