let's go crazy

Medical Provider Meeting 5/3/2016Community-University Health Care Center

• Long-acting insulins• SGLT-2 inhibitors• GLP-1 agonists• The future

• Insulin degludec - human insulin analog• Long-acting• Half-life >24 hours, detectable for 96 hours• Smooth, flat profile over 24 hours

• When compared to insulin glargine• No difference in glycemic control• Less variability• Less nighttime hypoglycemia

• FlexTouch Pens• U100 and U200 concentrations• What you click is what you get

• Conversion from Lantus 1:1• Lasts 56 days after opening

• U300 – more concentrated Lantus• Flatter, longer profile than U100• Duration of 24 hours, detectable for 36

hours• Similar efficacy to U100 glargine• Less hypoglycemia • Both overall and nighttime

• Cost similar to U100 on a unit-per-unit basis

• Conversion from Lantus• Start with 1:1 conversion• DM2 patients typically need 11-15% more• DM1 patients typically need 17.5% more• May have a temporary increase in FBG

• Insulin naïve patients may take 5 days to achieve full effect

• Use within 42 days

• Identical amino acid sequence to Lantus

• Available mid-December 2016• Only in pens (KwikPen)

• Now available in a pen – increased safety

• Acts like regular/NPH mix• Onset 30 minutes• Lasts up to 24 hours• 2-4 injections per day

• Names:• Canagliflozin (Invokana)• Dapagliflozin (Farxiga)• Empagliflozin (Jardiance)

• A1c decrease 0.6-1%• Modest weight loss in 12-week trials• Can decrease blood pressure

  INVOKANA (CANAGLIFLOZIN)

FARXIGA (DAPAGLIFLOZIN)

JARDIANCE (EMPAGLIFLOZIN)

STRENGTHS 100 mg, 300 mg 5 mg, 10 mg 10 mg, 25 mg

DOSING 1 tablet pre- breakfast 1 tablet QAM 1 tablet QAM

A1c REDUCTION (Alone) -0.77 to -1.16% -0.66 to -0.84% -0.85%

WEIGHT REDUCTION (Alone)

-2.8% (100 mg) -2.6% (5 mg) -2.8% (10 mg)

-3.9% (300 mg) -2.7% (10 mg) -3.2% (25 mg)

SBP REDUCTION -5.1 mmHg -4.5 to -5.3 mmHg -2.6 to -4.8 mmHg

COVERAGE

Blue Plus – Covered

HealthPartners – Step therapy

UCare – Step therapy Medica – Step therapy

HealthPartners – Step therapy  

Medica – Step therapy  

• Names:• Canagliflozin (Invokana)• Dapagliflozin (Farxiga)• Empagliflozin (Jardiance)

• A1c decrease 0.6-1%• Modest weight loss in 12-week trials• Can decrease blood pressure

• Dosage adjustments• Do not use if eGFR <45 mL/min/1.73m2

• Can use Invokana and Jardiance use if eGFR 45-60 mL/min/1.73m2

• Do not use Invokana in hepatic impairment• Adverse effects• Increased urinary frequency/urgency• Genital mycotic infection• UTI• Ketoacidosis

SGLT-2 Inhibition

Decreased CHO

availability

Increased lipolysis, lipid oxidation and

glucagon

Increased mobilization of FFAs and

TGs

Increased ketogenesis

Worsened by decreased

insulin/CHO intake

Increased ketones

Increased nausea

Decreased caloric intake,

volume depletion

BG mildly high,

increased insulin dose

Euglycemic DKA

• Prevention of euglycemic DKA• Contraindicated in Type 1 DM• Caution in patients where T1 vs T2 is in

question• Caution in patients making little endogenous

insulin• Educate on symptoms and situations of DKA• Nausea, vomiting, malaise• BG may be normal or slightly elevated• Insulin dose reductions, alcohol intake, illness

• Increased glucose-dependent insulin secretion

• Decreased glucagon secretion• Slowed gastric emptying• Increased satiety• Modest weight loss• A1c decrease 1-1.5%

• Mechanism of action:• Increased glucose-dependent insulin secretion• Decreased glucagon secretion• Slowed gastric emptying• Increased satiety

• Modest weight loss• Less hypoglycemia than other agents• A1c decrease 1-1.5%• Adverse effects

• Nausea• Risk of pancreatitis• Risk of thyroid c-cell tumors?

GLP-1 AGONIST FREQUENCY TARGETS

A1C REDUCTIO

N

WEIGHT LOSS (KG)

SPECIAL FEATURES

BYETTA 5 AND 10 mg BID POSTPRANDIAL 1% 2 ADMINISTER WITH

MEALS

VICTOZA 0.6-1.8 mg DAILY MIX 1.5% 2.5 DIAL OUT

BYDUREON 2 mg PEN/VIAL WEEKLY FASTING 1.5% 2.5 VIAL REQUIRES MIXING

TANZEUM WEEKLY FASTING 1% 1 DIFFICULT TO USE

TRULICITY WEEKLY FASTING 1.5% 2.5 AUTOINJECTOR

• Mix of Tresiba and Victoza• Mix of Tresiba and rapid-acting

insulin• Novolog in a FlexPen

• Rosenstock, J., & Ferrannini, E. (n.d.). Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors.Diabetes Care., 38(9), 1638-1642.

•  • Fineman, M., Cirincione, B., Maggs, D., & Diamant, M. (n.d.). GLP-1 based

therapies: Differential effects on fasting and postprandial glucose. Diabetes, Obesity & Metabolism, 14(8), 675-688.

•  • Simonson, Greg. Highlights of what’s new in diabetes. Presentation.

1.25.2016•  • Pharmacist’s Letter: GLP-1 agonists. Accessed 4.29.2016.•  • Pharmacist’s Letter: SGLT-2s. Accessed 4.29.2016.•  • Package inserts: Tresiba, Toujeo, Invokana, Jardiance, Farxiga