Newer Antidiabetic Drugs

Last Updated on 23rd August 2017 by Fiona Green

Introduction

1. A number of newer antidiabetic drugs have been approved for use recently, some without evidence of long term benefits and with inadequate safety data.
2. The most spectacular casualties have been the thiazoledinediones rosiglitazone and pioglitazone which are no longer used because of increased cardiovascular and cancer risks
3. The good news is that outcome trials are now being undertaken with results of some already available eg for liraglutide, empagaflozin and canaglifozin, while others will publish soon
4. You need to know about the following classes of drugs because patients who are admitted as emergencies may be taking them – they should only be initiated on specialist advice

Limitations of Older Therapies

1. Weight gain – sulphonylureas, pioglitazone, insulin
2. Hypoglycaemia – sulphonylureas, insulin
3. Concerns over CV safety – rosiglitazone
4. Concerns over cancer risks – pioglitazone,
5. Limited options in patients with renal disease – especially metformin although remember that metformin does not cause renal failure but can accumulate in people with renal failure increasing the risk of lactic acidosis. Metformin can be used in people with an eGfr of >30 and on specialist advise may be continued in those with a lower eGFR

Glucagon-Like Peptide 1 (GLP1) Analogues – The Tides

1. These are analogues of gut derived hormones called incretins, secreted in response to the ingestion of food that promote a number of metabolically beneficial responses
2. Incretins stimulate insulin secretion, inhibit glucagon release, delay gastric emptying and increase feeling of fullness
3. Liraglutide (Victoza) is given by once daily SC injection with no need for renal dose reduction
4. Others in class which include dulaglutide once weekly and exenetide once daily require renal dose reduction
5. Liraglutide reduced major atherosclerotic coronary events (MACE), CV deaths and total mortality, and was heart failure neutral in the LEADER trial
6. Exenetide and dulaglutide outcome trials awaited
7. Hypoglycaemia is rare
8. Useful when weight loss required
9. This group of drugs may cause pancreatitis so remember to look out for this when those taking it are admitted with abdominal pain or atypical chest pain

Dipeptidyl Peptidase-4 (DDP-4) Inhibitors – The Gliptins

1. These inhibit the enzyme that breaks down GLP1
2. Linagliptin is given once daily orally and requires no renal dose reduction
3. Others in class which include sitagliptin and saxagliptin require renal dose reduction
4. Trials suggest MACE neutral but possibly more hospitalisation for HF
5. Hypoglycaemia is rare
6. Weight neutral
7. This group of drugs may cause pancreatitis so remember to look out for this when those taking it are admitted with abdominal pain or atypical chest pain

SGLT2 Inhibitors – The Flozins

1. These inhibit SGLT2 in the proximal convoluted tubule of the kidney which decreases renal reabsorption of glucose
2. Empagiflozin is given once daily orally.and requires renal dose reduction: dont start if eGFR <60ml/min; decrease dose if eGFR falls below 60ml/min and stop if eGFR falls below 45ml/min
3. Others in class eg dapaglifozin and canaglifozin also require renal dose reduction
4. Empaglifozin reduced MACE, CV deaths, total mortality and hospitalisation for heart failure while canaglifozin reduced MACE and hospitalisation for heart failure in outcome trials
5. Side effects included genital infections (both drugs) and risk of amputation (canaglifozin) so long term safety uncertain
6. Hypoglycaemia is rare
7. Useful when weight loss required
8. SGLT2 inhibitors may predispose those taking it to diabetic ketoacidosis despite having type 2 diabetes. The risk is increased if the individual is fasting or has another reason for reduced intake. This dug should be temporarily stopped in acute illness to reduce this risk
9. May increase the risk of toe amputations. Remember to check the feet of all people with diabetes especially if they are taking this group of drugs