During a recent Diabetes Prescribing Group meeting at my integrated care board, the subject of tirzepatide was discussed, and there was some uncertainty as to the differences between a glucagon-like peptide-1 (GLP-1) receptor agonist and a dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, of which tirzepatide is the first in class.
Following this meeting, I compiled a list of key points with respect to tirzepatide.
- Tirzepatide is a synthetic peptide with agonist activity at both the GIP and GLP-1 receptors (with a greater affinity for the GIP receptor). It has a half-life of 5 days and hence, in the management of type 2 diabetes or obesity, it is administered as a weekly injectable.
- GLP-1 and GIP are incretin hormones (“incretin” is an acronym for INtestine seCRETion INsulin), and they facilitate the “incretin effect”, in which a higher level of insulin secretion is induced by oral administration of glucose than with intravenous administration, mainly owing to the release of incretin hormones (GIP and GLP-1). This effect allows “appropriate” release of insulin when blood glucose is high and suppression of insulin when blood glucose is low.
- GIP has a greater incretin effect than GLP-1 in people without diabetes but has been found to have a much reduced incretin effect in people with type 2 diabetes. This is a reason why it was not considered initially as a potential target for glucose-lowering therapy in type 2 diabetes. It was only when studies showed there to be a synergistic incretin effect, when combining GLP-1 and GIP in a single infusion, that this new treatment option became a possibility.
- GIP has a different effect on glucagon than GLP-1 and causes increased glucagon secretion when blood glucose is low or within the normal range. The GIP effect on glucagon is thought to affect muscle and liver glucose metabolism and to possibly be a contributing factor to the increased weight loss seen with combined GLP-1/GIP receptor agonists compared with GLP-1 receptor agonists (e.g. semaglutide).
- Adverse effects with tirzepatide have been found to be similar to those with GLP-1 receptor agonists. In SURPASS-2, a trial in which tirzepatide was compared with semaglutide as an add-on to metformin in type 2 diabetes, the most common adverse events in both arms were gastrointestinal in nature.
For further details with respect to tirzepatide, see GPnotebook.
Other highlights in this month’s email include updates on prostate cancer and exercise and on paracetamol use in pregnancy and breastfeeding.
- Prostate cancer and exercise: Does the evidence show that exercise reduces the incidence of prostate cancer or that it may slow the progression of prostate cancer? Or are both true?
- Paracetamol use in pregnancy and breastfeeding: What is the relationship between the use of paracetamol during pregnancy and the incidence of wheezing in offspring? What about the relationship between autism and the use of paracetamol during pregnancy? Is paracetamol the analgesia of choice during breastfeeding?
- Listeriosis: Listeriosis is a rare infection caused by Listeria monocytogenes, an aerobic gram-positive rod found in some semi-processed foods including soft cheeses and pâté; but can pregnant women acquire listeriosis from sheep at lambing time?
- Bacterial meningitis: This section of GPnotebook has been updated.
- Tirzepatide: This section of GPnotebook has been updated.