What are the concerns with using SGLT2 (Sodium-Glucose Linked Transporter 2) inhibitors, such as canagliflozin (canagliflozin), in a 92-year-old patient, particularly regarding weight loss and appetite suppression?

From the Guidelines

SGLT2 inhibitors like canagliflozin should generally be avoided in 92-year-old patients due to significant safety concerns, particularly regarding weight loss and appetite suppression, as well as other serious risks such as volume depletion, orthostatic hypotension, and increased risk of falls and fractures. These medications can cause problematic weight loss and appetite suppression in elderly patients who may already be frail or underweight 1. The mechanism of promoting glucose excretion through urine can lead to dehydration and electrolyte imbalances, which elderly patients are particularly susceptible to due to age-related decreases in thirst sensation and kidney function.

Some of the key concerns with using SGLT2 inhibitors in elderly patients include:

• Volume depletion and orthostatic hypotension, which can increase the risk of falls and fractures
• Urinary tract infections and genital mycotic infections
• Increased risk of euglycemic diabetic ketoacidosis
• Rare but serious adverse reactions, such as increased risk of ketoacidosis, acute kidney injury, bone fracture, and need for toe amputation (canagliflozin) 1

Alternative diabetes medications with better safety profiles in the elderly include DPP-4 inhibitors like sitagliptin or low-dose sulfonylureas, which should be considered instead after careful assessment of the patient's overall health status, comorbidities, and goals of care 1. It is essential to weigh the potential benefits of SGLT2 inhibitors against the potential risks and consider alternative treatment options that may be more suitable for elderly patients.

In terms of specific contraindications, SGLT2 inhibitors should be used with caution in patients with moderate renal impairment and discontinued in severe renal impairment 1. Additionally, patients with a history of ketoacidosis, acute kidney injury, or bone fracture should be carefully evaluated before initiating SGLT2 inhibitor therapy. Ultimately, the decision to use SGLT2 inhibitors in a 92-year-old patient should be made on a case-by-case basis, taking into account the individual patient's unique needs and health status.

From the FDA Drug Label

1. 7 Hepatic Impairment No dosage adjustment is necessary in patients with mild or moderate hepatic impairment. The use of INVOKANA has not been studied in patients with severe hepatic impairment and is therefore not recommended [see Clinical Pharmacology (12. 3)] .

10 OVERDOSAGE In the event of an overdose, contact the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.

Efficacy and safety trials with INVOKANA did not enroll adult patients with ESKD on dialysis or patients with an eGFR less than 30 mL/min/1.73 m 2[see Clinical Pharmacology (12.3)] .

The contraindications for SGLT2 inhibitors, such as canagliflozin, include:

• Severe hepatic impairment
• Patients with ESKD on dialysis
• Patients with an eGFR less than 30 mL/min/1.73 m^2

Regarding weight loss and appetite suppression in a 92-year-old patient, the provided drug labels do not directly address these concerns. However, it is essential to consider the potential risks of hypotension and acute kidney injury in patients with renal impairment, which may be more likely in elderly patients 2.

Given the lack of direct information on weight loss and appetite suppression, it is crucial to closely monitor the patient's condition and adjust the treatment plan as needed to minimize potential risks.

Key considerations for the use of SGLT2 inhibitors in elderly patients:

• Renal function
• Hepatic function
• Risk of hypotension
• Risk of acute kidney injury

It is recommended to consult the patient's healthcare provider to discuss the potential benefits and risks of using SGLT2 inhibitors in this population 2.

From the Research

Contraindications for SGLT2 Inhibitors

• Severe renal impairment is a contraindication for the use of SGLT2 inhibitors, as their effectiveness decreases with increasing severity of renal impairment 3.
• Hepatic impairment is also a consideration, and SGLT2 inhibitors should not be prescribed for individuals with severe hepatic impairment 4.
• Patients with a history of urogenital infections or those on diuretics should be carefully evaluated before the administration of SGLT2 inhibitors 4.

Weight Loss and Appetite Suppression

• SGLT2 inhibitors can assist with weight loss due to the increased renal glucose elimination, which can also help reduce blood pressure 5, 3.
• The effect of SGLT2 inhibitors on weight loss is consistent across trials, and this can be beneficial for patients with type 2 diabetes mellitus 5.
• However, in a 92-year-old patient, caution is recommended due to the higher risk of renal impairment, orthostatic hypotension, and dehydration 5.
• There is no direct mention of appetite suppression as a concern with SGLT2 inhibitors in the provided studies, but the weight loss effect may be a consideration in elderly patients who may already be at risk of malnutrition or dehydration.

Considerations for Elderly Patients

• Elderly patients, especially those with renal impairment, should be carefully monitored when using SGLT2 inhibitors due to the potential risks of orthostatic hypotension, dehydration, and renal function decline 5, 3.
• The benefits of SGLT2 inhibitors, including their unique mechanism of action and low risk of hypoglycemia, should be weighed against the potential risks in elderly patients 5.