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.
On this episode I discuss empagliflozin pharmacology and how this medication lowers blood sugar.
In this episode, I talk about empagliflozin pharmacology. Empagliflozin is more commonly known by the brand name Jardiance and is in the class of sodium-glucose co-transporter-2 inhibitors or SGLT2 inhibitors. Jardiance use has definitely escalated over the last few years in the management of type 2 diabetes, but this has been changing a little bit as well due to recent evidence for the cardiovascular benefits from this medication.
The sodium-glucose co-transporter-2 is found in the kidney and is responsible for helping the body reabsorb glucose back into the bloodstream. The way empagliflozin works is by inhibiting this transporter, more glucose is excreted into the urine and ultimately lowering the blood sugar since it is not being reabsorbed. Empagliflozin has additional benefits outside of blood sugar reductions. Studies found that patients with or without diabetes receive cardiovascular protective effects from this medication, including a reduction in heart failure hospitalizations and reducing the risk of death in patients with ASCVD. Additionally, empagliflozin has shown some benefits in protecting renal function over time in patients with and without chronic kidney disease (CKD).
Dosing is pretty straightforward for this medication. Empagliflozin is taken once daily and is an oral medication, which is nice for patients who do not want injectable therapy. Dosing starts at 10 mg once daily and may be increased up to 25 mg daily if tolerated. This increase is typically done after about 4 weeks to see if it is needed. In patients with renal dysfunction and an eGFR less than 45 mL/min, FDA labeling states that empagliflozin should not be initiated, although there is a gray area in the 30-45 mL/min range that needs further study.
When thinking about the side effects of empagliflozin, it is helpful to keep the mechanism of action in mind, where we are increasing the urinary glucose. This can also lead to more fluid being excreted with the glucose, causing a decrease in blood pressure and dehydration risks. This is important to keep in mind for patients who are more prone to hypotension, including elderly patients. Empagliflozin also causes increased genitourinary fungal infections and UTIs due to the increase in sugar in the urine. Other rare adverse effects include ketoacidosis, necrotizing fasciitis risk, bone fracture, and lower limb amputation, however, this one has more controversial evidence.
For monitoring parameters, assessing A1c reduction and blood sugars is definitely important in our patients with diabetes. Patients on empagliflozin should also have their renal function monitored, as well as any blood pressure lowering. It is also important to keep an eye on any prescribing of antifungals, the incidence of UTIs, and assessing for signs of ketoacidosis.
The most important and common drug interactions are typically associated with additive effects with empagliflozin. Diuretic use can increase the risk for dehydration and hypotension. Additive blood sugar-lowering effects when empagliflozin is used with other agents such as insulin and sulfonylureas and can increase the patient’s risk for hypoglycemic episodes. Finally, blood pressure medication dosages may need to be reduced if empagliflozin is causing hypotension. Since empagliflozin is not hepatically metabolized, CYP450 drug interactions are not a problem.
Empagliflozin. Micromedex DrugDex. IBM Micromedex. Accessed July 29, 2021.Yusuf T, Raji YR, Lasisi TJ, et al. Predictors of taste dysfunction and its severity among patients with chronic kidney disease. Ear Nose Throat J. Published online July 19, 2021. doi:10.1177/01455613211019708.
On this episode, I discuss the pharmacology of oral semaglutide. It is a GLP-1 agonist that is the first one in the class to have an oral formulation.
There is a recommended dose titration with oral semaglutide that can take a month or two to get therapeutic doses. I disucss this further in this episode.
The most common adverse effect of oral semaglutide is nausea.
Oral semaglutide is dosed once daily which is nice to try to maximize patient adherence.
