Published: 1 December 2022
Publications
Risk of hypoglycaemia with newer antidiabetic medicines
Prescriber Update 43(4): 58–60
December 2022
The Centre for Adverse Reactions Monitoring (CARM) has received 2 case
reports of hypoglycaemia associated with newer antidiabetic medicines
(one report with vildagliptin and one with empagliflozin). Healthcare
professionals should monitor for and discuss the risks of hypoglycaemia
when prescribing medicines to treat type 2 diabetes mellitus (T2DM).
Pharmacological treatment of type 2 diabetes mellitus
Pharmacological treatment with glucose-lowering medicines aims to lower HbA1c levels and reduce the risk of diabetes complications.1
Many medicines are available to treat T2DM, and the choice of medicine depends on the patient’s overall health status, co-morbidities, and risks associated with hypoglycaemia.1 Metformin, insulin and sulfonylureas (eg, gliclazide, glipizide) are well-known antidiabetic medicines. Newer antidiabetic medicines approved and available in New Zealand include:- glucagon-like peptide 1 (GLP-1) receptor agonists: dulaglutide, exenatide
- sodium-glucose co-transporter 2 (SGLT-2) inhibitors: dapagliflozin, empagliflozin
- dipeptidyl peptidase-4 (DPP-4) inhibitors: saxagliptin, vildagliptin.
Hypoglycaemia
Hypoglycaemia in patients with diabetes is defined as all episodes of an abnormally low plasma glucose concentration (with or without symptoms) that expose the individual to harm.2 There is no specific glucose level that defines hypoglycaemia and the glycaemic thresholds that induce symptoms vary between individuals.3 Hypoglycaemia is associated with an increased risk of falls and cognitive impairment and may increase the risk of mortality.1
Hypoglycaemia is known to occur with insulin and sulfonylureas.4 GLP-1 receptor agonists, SGLT-2 inhibitors and DPP-4 inhibitors are not typically associated with hypoglycaemia when used as monotherapy,3 although cases have been reported. The risk of hypoglycaemia increases with concomitant use of insulin and/or a sulfonylurea.3Mechanism of action
GLP-1 receptor agonists and DPP-4 inhibitors increase the levels of incretin hormones (glucagon-like peptide 1 and glucose-dependent insulinotropic polypeptide).5,6 Increased levels of these hormones enhance beta cell glucose sensitivity, resulting in improved glucose-dependent insulin secretion and reduced blood glucose.5,6 Due to this enhanced beta cell sensitivity, patients taking concomitant insulin or a sulfonylurea may require a lower dose of their insulin or sulfonylurea to prevent episodes of hypoglycaemia.6
Hypoglycaemia was a very common adverse reaction (frequency ≥1/10) reported in clinical trials of patients taking SGLT-2 inhibitors with concomitant insulin or sulfonylureas.7 SGLT-2 inhibitors promote glucose excretion by reducing renal absorption of glucose into the blood stream. Patients on concomitant therapy may require a lower dose of their insulin or sulfonylurea to prevent episodes of hypoglycaemia.7CARM reports
As of 30 September 2022, CARM had received the following reports of hypoglycaemia associated with newer antidiabetic medicines.- Vildagliptin (CARM ID: 138371) – a patient on insulin experienced hypoglycaemia after starting treatment with vildagliptin. The insulin dose was decreased, and they were reported to have recovered.
- Empagliflozin (CARM ID: 142383) – the patient experienced hypoglycaemia after their empagliflozin dose was increased.
References
- bpacNZ. 2021. Type 2 diabetes management toolbox: from lifestyle to insulin 25 August 2021. URL: bpac.org.nz/2021/diabetes-management.aspx (accessed 19 September 2022).
- Seaquist ER, Anderson J, Childs B, et al. 2013. Hypoglycemia and diabetes: a report of a workgroup of the American Diabetes Association and the Endocrine Society. Journal of Clinical Endocrinology & Metabolism 98(5): 1845-59. DOI: 10.1210/jc.2012-4127 (accessed 19 September 2022).
- Cryer P. 2022. Hypoglycemia in adults with diabetes mellitus. In: UpToDate 3 August 2022. URL: uptodate.com/contents/hypoglycemia-in-adults-with-diabetes-mellitus (accessed 19 September 2022).
- Ibrahim M, Baker J, Cahn A, et al. 2020. Hypoglycaemia and its management in primary care setting. Diabetes Metabolism Research and Reviews 36(8): e3332. DOI: 10.1002/dmrr.3332 (accessed 18 September 2022).
- Novartis New Zealand. 2022. Galvus New Zealand Data Sheet 20 May 2022. URL: medsafe.govt.nz/profs/datasheet/g/galvustab.pdf (accessed 15 September 2022).
- Eli Lilly and Company Limited. 2021. Trulicity New Zealand Data Sheet 12 August 2021. URL: medsafe.govt.nz/Profs/Datasheet/t/trulicityinj.pdf (accessed 19 September 2022).
- Boehringer Ingelheim. 2022. Jardiance NZ Data Sheet 17 June 2022. URL: medsafe.govt.nz/profs/Datasheet/j/jardiancetab.pdf (accessed 15 September 2022).