Sodium-glucose co-transporter 2 (SGLT2) inhibitors and their place in therapy

Katee Lira, PharmD PGY2 Ambulatory Care Pharmacy ResidentSt. Vincent Joshua Max Simon Primary Care CenterSeptember 18, 2014

This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation.

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Objectives

• Recall the mechanism of action of SGLT2 inhibitors

• List potential benefits and concerns of SGLT2 inhibitors

• Recognize available SGLT2 inhibitors and appropriate dosing

• Identify place in therapy for SGLT2 inhibitors

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Components that Affect Hyperglycemia

DeFronzo RA. Diabetes. 2009;58:773-795.

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How Do SGLT2 Inhibitors Work?

Glucose in blood

Glucosuria

Chao EC, et al. Nat Rev Drug Discovery. 2010;9:551-559.

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What % A1c Reduction will SGLT2 Inhibitors Have?

0.5% 1% 1.5% 2%

Diabetes Care 2014;37: S14-79.

DPP4 inhibitors

SGLT2 inhibitors

TZDs MetforminSulfonylureas

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Highlights of SGLT2 Inhibitors

• Indication: adults with type 2 diabetes (T2DM)•Not approved for <18 years old, T1DM, or DKA

• Ongoing studies•Pediatrics•CV outcomes

• Benefits•Weight reduction: ~2-3kg•Systolic blood pressure lowering: ~3-5mmHg•Low risk of hypoglycemia

List JF, et al. Diabetes Care. 2009;32:650-657. Stenlof K, et al. Diabetes Obes Metab. Published online January 24, 2013.

Invokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2013.Farxiga™ [package insert. Wilmington, DE: AstraZeneca. 2014.

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FDA Approved SGLT2 Inhibitors

Invokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2013.Farxiga™ [package insert]. Wilmington, DE: AstraZeneca. 2014.Jardiance® [package insert]. Ridgefield, CT. Boehringer Ingelheim Pharmaceuticals, Inc. 2014.

Agent Canagliflozin INVOKANA®

Dapagliflozin FARXIGA™

Empagliflozin JARDIANCE®

Dosing Initial: 100mg dailyMax: 300mg daily

Initial: 5mg daily Max: 10mg daily

Initial: 10mg daily Max: 25mg daily

Administration Before the first meal of the day

In the morning with or without food

In the morning with or without food

Renal Dose Adjustments

Yes Yes Yes

Cost ~$350 for 30 tablets

~$350 for 30 tablets

TBD

Patient Assistance

Available Available TBD

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Warnings for SGLT2 Inhibitors

• Increased urination • Vaginal yeast infections• Urinary tract infections• Nasopharyngitis

(dapagliflozin)

• Hypotension • Impairment in renal function• Hyperkalemia• Hypoglycemia• Hypersensitivity • Increase in LDL • Bladder cancer

(dapagliflozin)

ISMP High Alert Medication – Dispense with Medication Guide

Invokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2013.Farxiga™ [package insert. Wilmington, DE: AstraZeneca. 2014.

Adverse drug reactions Precautions

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Place in Therapy – Monotherapy

• Recent-onset diabetes and mild hyperglycemia (A1c≤7.5%)

• Metformin is preferred

• If intolerance or contraindication to metformin

• SGLT2 inhibitors compared to placebo •Decreasing A1c•Decrease fasting glucose

Diabetes Care 2014;37: S14-79.Ferrannini E, et al. Diabetes Care. 2010;33(10):2217-2224.

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Place in Therapy – Combination Therapy

• Initial A1c >7.5% – start dual therapy

• Target A1c not reached in 3 months with metformin – add second agent

• No preferred agent to be combined with metformin

• SGLT2 inhibitors studies have demonstrated improved glycemic control with combination and add-on therapy•Metformin•Sulfonylurea•Thiazolidinedione•Insulin

Diabetes Care 2014;37: S14-79.Bailey CJ, et al. Lancet. 2010;375(9733):2223-2233.

Strojek K, et al. Abstract 870. EASD 2010.Wilding JPH, et al. Abstract 78-OR. ADA 2010. Bailey CJ et al. Abstract 988-P. ADA 2011.

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Patient Centered Approach When Considering SGLT2 Inhibitors

• Effectiveness independent of insulin

• Can ↓ A1c by ~1%• Combine with other oral

anti-diabetics and insulin• Low risk for hypoglycemia • Small amount of weight loss• Small ↓ in blood pressure

• Adequate renal function required

• ↑ urinary frequency• Electrolyte disturbances• ↑ risk of UTIs and vaginal

yeast infections• Orthostatic hypotension• Lipid abnormalities (↑ LDL)• Cost

Pros Cons

Diabetes Care 2014;37: S14-79.

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Assessment Question

Which of the following is a counseling point to tell a patient being started on canagliflozin?

A. Will cause significant weight lossB. Take before the last meal of the day C. May increase your risk of urinary tract infectionsD. Has a high risk of hypoglycemia in combination with metformin

Sodium-glucose co-transporter 2 (SGLT2) inhibitors and their place in therapy

Katee Lira, PharmD PGY2 Ambulatory Care Pharmacy ResidentSt. Vincent Joshua Max Simon Primary Care CenterSeptember 18, 2014

This speaker has no actual or potential conflicts of interest to disclose in relation to this presentation.