Download SGLT-2 Inhibitors: Overview and Place in Therapy

9/8/2015
SGLT-2 Inhibitors:
Overview and Place in Therapy
Kelsey Gander, PharmD
Ambulatory Care Clinical Pharmacist
Mayo Clinic Health System – Mankato, MN
Disclosure
• Nothing to disclose
Objective
• Describe the appropriate clinical use of SGLT-2
inhibitors for treating diabetes
– Canagliflozin
– Dapagliflozin
– Empagliflozin
• SGLT = Sodium-Glucose Cotransporter
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Indication
• Treatment of type 2 diabetes mellitus as an
adjunct to diet and exercise to improve
glycemic control
Mechanism of Action
http://blogs.nature.com/houseofwisdom/2015/02/revolutionary-type-2-diabetes-therapy-to-be-released-soon.html
Comparative Efficacy
Medication
Mean A1c Decrease
Canagliflozin
100-300mg daily
Monotherapy: 0.77-1.03%1
Combo therapy: 0.63-1.06%2,3,4
Dapagliflozin
5-10mg daily
Monotherapy: 0.41-1.11%5,6
Combo therapy: 0.5-0.97%7,8,9,10,11
Empaglifozin
10-25mg daily
Monotherapy: 0.5-0.85%12,13
Combo therapy: 0.6-1%14,15,16,17
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Other Effects Noted in Clinical Trials
• Decreased fasting and postprandial glucose
• Systolic blood pressure decrease
– Approximately 2-10mmHg
• Weight loss
– Up to 4.7kg
• Decreased uric acid
• Small increases in LDL and HDL cholesterol
Renal Dose Adjustments
• Canagliflozin
– eGFR 45-60 do not exceed 100mg daily
• eGFR <45 do not use
• Dapagliflozin
– eGFR <60 do not use
• Empagliflozin
– eGFR <45 do not use
Safety
• Side effects:
–
–
–
–
Genital mycotic infections (females>males)
Urinary tract infection
Postural dizziness/orthostatic hypotension
Polyuria
• Low risk of hypoglycemia
– Unless used in combination with sulfonylurea or
insulin
• Dapagliflozin: risk of bladder cancer11
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Safety
• FDA Warning: Ketoacidosis
– FDA review identified 20 cases of acidosis in
patients treated with SGLT2 inhibitors from March
2013-June 2014
– S/S: Difficulty breathing, nausea, vomiting,
abdominal pain, confusion, unusual
fatigue/sleepiness
– Risk factors: major illness, reduced food and fluid
intake, and reduced insulin dose18
Convenience
• Once-daily dosing
• Also a few combination products available:
– Canagliflozin + IR metformin: dosed twice daily
– Dapagliflozin + ER metformin: dosed once daily
– Empagliflozin + linagliptin
• Cost:
– Approximately $400 per month
– “$0” copay cards available through manufacturers
for private insurance
Place in Therapy
• ADA guidelines:
– Second line therapy in addition to metformin if not at
goal
• AACE guidelines:
– Can be used as monotherapy or in addition to other
agents as part of dual or triple therapy
• Key advantages:
– Oral medication
– Low risk of hypoglycemia
– Potential for weight loss
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Case
• XY is a 51 year old Caucasian male who
presents to clinic today for follow-up DM
appointment.
– Current diabetes medications:
• Metformin XR 2000mg daily
– Labs prior to visit:
• A1c 7.6%, SCr 1.1, eGFR >60
– Vitals:
• BMI 32.5, BP 136/78 mmHg, Pulse 88 bpm
What would be the advantages of adding an
SGLT-2 inhibitor to this patient’s regimen?
a) A1c reduction adequate to reach goal (<7%)
b) Weight loss
c) Low risk of hypoglycemia when added to
metformin
d) All of the above
References
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Stenlof K, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and
exercise. Diabetes Obes Metab. 2013 Apr;15(4):372-82.
Forst T, et al. Efficacy and safety of canagliflozin over 52 weeks in patients with type 2 diabetes on background metformin and pioglitazone.
Diabetes Obes Metab. 2014 May; 16(5): 467–477.
Product Information: INVOKANA(TM) oral tablets, canagliflozin oral tablets. Janssen Pharmaceuticals, Inc. (per manufacturer), Titusville, NJ, 2014.
Schernthaner G, et al. Canagliflozin compared with sitagliptin for patients with type 2 diabetes who do not have adequate glycemic control with
metformin plus sulfonylurea: a 52-week randomized trial. Diabetes Care. 2013 Sep;36(9):2508-15.
Kaku K, et al. Efficacy and safety of dapagliflozin monotherapy in Japanese patient with type 2 diabetes inadequately controlled by diet and
exercise. Diabetes Obes Metab. 2014 Nov;16(11):1102-10.
Ji L, et al. Dapagliflozin as monotherapy in drug-naive Asian patients with type 2 diabetes mellitus: a randomized, blinded, prospective phase III
study. Clin Ther. 2014 Jan 1;36(1):84-100.
Schumm-Draeger PM, et al. Twice-daily dapagliflozin co-administered with metformin in type 2 diabetes: a 16-week randomized, placebocontrolled clinical trial. Diabetes Obes Metab. 2015 Jan;17(1):42-51.
Jabbour SA, et al. Dapagliflozin is effective as add-on therapy to sitagliptin with or without metformin: a 24-week, multicenter, randomized,
double-blind, placebo-controlled study. Diabetes Care. 2014;37(3):740-50.
Bailey CJ, et al. Dapagliflozin add-on to metformin in type 2 diabetes inadequately controlled with metformin: a randomized, double-blind,
placebo-controlled 102-week trial. BMC Med. 2013 Feb 20;11:43.
Rosenstock J, et al. Effects of dapagliflozin, an SGLT2 inhibitor, on HbA1c, body weight, and hypoglycemia risk in patients with type 2 diabetes
inadequately controlled on pioglitazone monotherapy. Diabetes Care. 2012 Jul;35(7):1473-8.
Product Information: FARXIGA oral tablets, dapagliflozin oral tablets. Bristol-Myers Squibb Company (per manufacturer), Princeton, NJ, 2014.
Roden M, et al. Empagliflozin monotherapy with sitagliptin as an active comparator in patients with type 2 diabetes: a randomised, double-blind,
placebo-controlled, phase 3 trial. Lancet Diabetes Endocrinol. 2013 Nov;1(3):208-19.
Ferrannini E, et a;/ A PhaseIIb, randomized, placebo-controlled study of the SGLT2 inhibitor empagliflozin in patients with type 2 diabetes.
Diabetes Obes Metab. 2013 Aug;15(8):721-8
Haring HU, et al. Empaglifozin as add-on to metformin in patients with type 2 diabetes: a 24-week, randomized, double-blind, placebo-controlled
trial. Diabetes Care. 2014 Jun;37(6):1650-9.
Haring HU, et al. Empagliflozin as add-on to metformin plus sulfonylurea in patient with type 2 diabetes: a 24-week, randomized, double-blind,
placebo-controlled trial. Diabetes Care. 2013 Nov;36(11):3396-404.
Kovacs CS, et al. Empagliflozin improves glycemic and weight control as add-on therapy to pioglitazone or pioglitazone plus metformin in patients
with type 2 diabetes: a 24-week, randomized, placebo-controlled trial. Diabetes Obes Metab. 2014 Feb;16(2):147-58.
Product Information: JARDIANCE(R) oral tablets, empagliflozin oral tablets. Boehringer Ingelheim Pharmaceuticals (per manufacturer), Ridgefield,
CT, 2014.
Food and Drug Administration. FDA Drug Safety Communication: FDA warns that SGLT2 inhibitors for diabetes may result in a serious condition of
too much acid in the blood. http://www.fda.gov/Drugs/DrugSafety/ucm446845.htm. Accessed 2015Aug 21.
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9/8/2015
SGLT-2 Inhibitors:
Overview and Place in Therapy
Kelsey Gander, PharmD
Ambulatory Care Clinical Pharmacist
Mayo Clinic Health System – Mankato, MN
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