Sodium-glucose co-transporter 2 (SGLT2)
inhibitors and their place in therapy
Katee Lira, PharmD
PGY2 Ambulatory Care Pharmacy Resident
St. Vincent Joshua Max Simon Primary Care Center
September 18, 2014
This speaker has no actual or potential conflicts of
interest to disclose in relation to this presentation.
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
2
Components that Affect Hyperglycemia
3
DeFronzo RA. Diabetes. 2009;58:773-795.
How Do SGLT2 Inhibitors Work?
Glucose in blood
Glucosuria
4
Chao EC, et al. Nat Rev Drug Discovery. 2010;9:551-559.
What % A1c Reduction will SGLT2 Inhibitors Have?
0.5%
DPP4
inhibitors
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Diabetes Care 2014;37: S14-79.
1%
SGLT2
inhibitors
1.5%
TZDs
2%
Metformin
Sulfonylureas
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
6
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.
FDA Approved SGLT2 Inhibitors
Agent
Canagliflozin
INVOKANA®
Dapagliflozin
FARXIGA™
Dosing
Initial: 100mg daily Initial: 5mg daily
Max: 300mg daily Max: 10mg daily
Empagliflozin
JARDIANCE®
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
7
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.
Warnings for SGLT2 Inhibitors
Adverse drug reactions
•
•
•
•
Increased urination
Vaginal yeast infections
Urinary tract infections
Nasopharyngitis
(dapagliflozin)
Precautions
•
•
•
•
•
•
•
Hypotension
Impairment in renal function
Hyperkalemia
Hypoglycemia
Hypersensitivity
Increase in LDL
Bladder cancer
(dapagliflozin)
ISMP High Alert Medication – Dispense with Medication Guide
8
Invokana® [package insert]. Titusville, NJ: Janssen Pharmaceuticals, Inc. 2013.
Farxiga™ [package insert. Wilmington, DE: AstraZeneca. 2014.
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
9
Diabetes Care 2014;37: S14-79.
Ferrannini E, et al. Diabetes Care. 2010;33(10):2217-2224.
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
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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.
Patient Centered Approach When Considering
SGLT2 Inhibitors
Pros
• 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
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Diabetes Care 2014;37: S14-79.
Cons
• Adequate renal function
required
• ↑ urinary frequency
• Electrolyte disturbances
• ↑ risk of UTIs and vaginal
yeast infections
• Orthostatic hypotension
• Lipid abnormalities (↑ LDL)
• Cost
Assessment Question
Which of the following is a counseling point to tell a patient being
started on canagliflozin?
A. Will cause significant weight loss
B. Take before the last meal of the day
C. May increase your risk of urinary tract infections
D. Has a high risk of hypoglycemia in combination with metformin
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Sodium-glucose co-transporter 2 (SGLT2)
inhibitors and their place in therapy
Katee Lira, PharmD
PGY2 Ambulatory Care Pharmacy Resident
St. Vincent Joshua Max Simon Primary Care Center
September 18, 2014
This speaker has no actual or potential conflicts of
interest to disclose in relation to this presentation.