Antidiabetic medications

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