On this episode I discuss the pharmacology of tirzepatide. I’m appreciative of Derek Borkowski who operates Pyrls for providing a free PDF of the 2023 ADA Diabetes Guidelines when you subscribe for an account at Pyrls.com/rlp – Tirzepatide makes its first appearance in the diabetes guidelines for its ability to promote weight loss.
Tirzepatide is a combination GIP and GLP-1 agonist that is currently indicated for diabetes with reductions of A1C in the range of about 2 points.
Much like GLP-1 agonists, tirzepatide can cause GI upset and other gastrointestinal adverse effects like diarrhea.
Tirzepatide doesn’t have a large number of drug interactions which is nice. Corticosteroids can counteract its blood sugar-lowering effects while sulfonylureas and insulin may significantly increase the risk for hypoglycemia.
Sitagliptin is a DPP4 inhibitor. I discuss the pharmacology of this medication on the podcast.
Which diabetes medication works similarly to sitagliptin? I discuss that further on this episode of the Real Life Pharmacology podcast.
Renal elimination plays a significant role with sitagliptin. I discuss how this impacts the appropriate dosing.
Cost is a significant issue with sitagliptin at this time. In addition, it’s A1C-lowering effects aren’t anything to write home about. I discuss how much it will lower A1C in this podcast episode.
Canagliflozin is an SGLT2 inhibitor. I discuss the pharmacology, dosing, adverse effects, and drug interactions of this medication.
Canagliflozin reduces blood sugar, by facilitating its exit through the urine. This can increase the risk of genitourinary infections.
A diuresis type effect can happen due to canagliflozin and this effect may be exacerbated by the use of thiazide and loop diuretics.
Hyperkalemia has been reported with the use of canagliflozin; the risk for this is increased with the use of medications like ACE inhibitors, ARBs, and aldosterone antagonists.
On this episode, I discuss liraglutide pharmacology, drug interactions, and adverse effects.
Liraglutide is well known to cause nausea. It is important to assess the severity of nausea as it may subside in some patients as they gain tolerability to the medication.
We mentioned the 2022 Diabetes Guideline Cheat Sheet in the podcast – you can get that for free at pyrls.com/rlp
Liraglutide has a fairly low risk of hypoglycemia when used alone, but this risk increases when it is used with insulin or sulfonylureas.
Saxenda is the weight loss formulation of liraglutide and dosing is higher for weight management than it is for diabetes management.
Glipizide, or Glucotrol, is a sulfonylurea used for the treatment of Type 2 Diabetes. Pharmacologically, glipizide acts by stimulating beta-cells in the pancreas to release insulin. Specifically, glipizide will block the opening of ATP-sensitive potassium channels on the plasma membrane of beta-cells on the pancreas. The result of that is depolarization, which then causes stimulation of voltage-sensitive calcium channels, eventually causing the exocytosis of insulin. The increased insulin will then promote the storage of glucose, decreasing the amount of glucose in the blood.
Due to the pharmacology of glipizide, the concerning adverse drug reactions are hypoglycemia and weight gain. Other adverse drug reactions include diaphoresis, dizziness, syncope, nervousness, anxiety, tremors, and diarrhea. The contraindications include hypersensitivity, Type 1 Diabetes, and DKA. Glipizide is not used as often due to the risk of hypoglycemia and weight gain. Glipizide is usually dosed once daily, but it can be split up if the dose is escalated. There are differences in administration depending on the formulation. For immediate release formulations, glipizide should be taken 30 minutes before meals to ensure that absorption is stable. For extended formulations, it can be given with breakfast or any other meal.
Of all the sulfonylureas, glipizide is preferred in CKD. Other sulfonylureas, like glyburide, are not preferred due to a decrease in elimination that can result in dose accumulation. In geriatric populations, dosing is less aggressive to lessen the risk of any adverse drug reactions and more specifically hypoglycemia. There’s a risk of cross-reactivity with sulfonamide allergies, but the risk will vary and is low risk. If SJS occurs due to a sulfonamide-containing drug, glipizide likely wouldn’t be recommended.
The drug-drug interactions of glipizide include medications that can increase the risk of hypoglycemia, for example, medications like quinolone antibiotics and B-blockers can mask the symptoms of hypoglycemia. Other interactions include the type where it can counteract the effect of glipizide, for example, medications that can increase blood glucose levels like corticosteroids, antipsychotics such as olanzapine and clozapine, stimulants, and transplant medications like cyclosporine and tacrolimus. There are also CYP interactions that can impact glipizide since it’s metabolized by CYP2C9. More monitoring is warranted when medications that can inhibit CYP2C9, like fluconazole, and medications that can induce CYP2C9, like rifampin, are also given. In cases of overdose, hypoglycemia is most likely to occur. Correction of decreased glucose levels is necessary.
Show notes provided by Chong Yol G Kim, PharmD Student.
