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3/1/2018

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New Pathways to Glycemic Control in

Type 2 Diabetes: A Look at the Oral Agents

Amelie Hollier, DNP, FNP-BC, FAANPPresident, CEO APEA

Lafayette, LA

Objectives• Evaluate and compare generic

pharmacologic agents to help manage hyperglycemia in adults who have Type 2 diabetes.

• Evaluate and compare newerpharmacologic agents to help manage hyperglycemia in adults who have Type 2 diabetes.

• Evaluate and compare outcomes when combinations of antihyperglycemic agents are used to help manage special populations of patients who have Type 2 diabetes.

Metformin HCl• Galega officinalis• Herb with white, purple, blue flowers

• Used in medieval times for “frequent urination”

Metformin HCl• In Europe 1957 “glucose eater”• Available in Canada in 1972• March 3, 1995 on US market

Metformin, 2018• Inhibits production of glucose

• Inhibits intestinal absorption of glucose

• Increases insulin sensitivity in muscle and fat

Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. http://www.clinicalpharmacology.com. (Accessed January 6, 2018).

Metformin, 2018• May reduce cardiovascular mortality, especially in obese patients (Level A)

• May reduce cardiovascular events


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Metformin, 2018• Preferred INITIAL agent (Level A)• Effective, safe, inexpensive (generic)

• Safe in pregnancy

1.Holman RR, Paul SK, Bethel MA, Matthews DR, Neil HAW. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med2008;359:1577–15892. Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med 2016;164:740–751.

Metformin HCl• Up to 30% have GI side effects• 5% completely intolerant• Up to 50% can’t tolerate target dose (2000 mg daily)

Initiation of Metformin IR

• Metformin IR 500 mg daily• Metformin IR 250 mg daily• Metformin liquid 100mg /ml

Increasing Dose of Metformin

• For IR or ER, increase by 500 mg per day every 1-2 weeks

• Could increase by 250 mg every 1-2 weeks

• Could take 4-8 weeks to reach target dose

Tips for Toleration

• Take with food, during or right after meals

• Take with evening meal (largest meal of day)

• Consider IR 3 times daily• Consider ER 2 times daily

Metformin HCl• ER may be better tolerated than IR

• ER has slower time to peak plasma concentration

• Metformin + drug release controlling polymers + GI fluid = Gel Matrix

• Peristalsis breaks down the matrix

1.Kim CH, Han KA, Oh HJ, et al. Safety, tolerability, and efficacy of metformin extended-release oral antidiabetic therapy in patients with type 2 diabetes: an observational trial in Asia. J Diabetes 2012;4:395-406.

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Metformin HCl• Components of tablet MAY remain intact in feces (soft, hydrated mass)

• Not uncommon with timed release tablets

• “Ghost tablet”

Cost Comparisons Metformin IR vs ER• Glucophage XR 500 mg, 750 mg• Fortamet 500 mg, 1000 mg• Glumetza 500 mg, 1000 mg

• Very little price difference between generic Glucophage IR and Glucophage XR

Diarrhea that Develops after years on Metformin…

• UN-USUAL!• Trial off metformin for 2-3 days • Usually needs further investigation

Product information for Glucophage and Glucophage XR. Bristol-Myers Squibb Company. Princeton, NJ 08543. January 2009.

Dehydration and Metformin

Teach patient to stop metformin if:• Dehydrated (nausea, vomiting, dehydration)

• Aggressive diuresis (as in unstable heart failure)

American Diabetes Association. Standards of Medical Care in Diabetes 2016. Diabetes Care 2016;39(Suppl 1):S1-S112.

HF and Metformin• 2006: FDA removed absolute contraindication of HF and metformin therapy

• Unstable or acute HF, risk of hypo-perfusion and hypoxemia close monitoring, high risk of lactic acidosis

• May need to discontinue metformin until exacerbation resolved

Metformin and Lactic acidosis

• Metformin-induced lactic acidosis: Rare!

• 3 in 30,000 patient-years• 50% fatality rate when on metformin

Salpeter SR, Greyber E, Pasternak G, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin in type 2 diabetes mellitus. Cochrane Database Syt Rev 2010;(4):CD002967.

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Metformin Excretion• Eliminated unchanged by kidneys

• Safe even with mild to moderate renal dysfunction

• “Recent” FDA labeling change

• Can be used with eGFR > 30 ml/min/1.73m2

Frid A, Sterner GN, Löndahl M, et al. Novel assay of metformin levels in patients with type 2 diabetes and varying levels of renal function: clinical recommendations. Diabetes Care 2010;33:1291-3.

Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. April 8, 2016.

Metformin for Special Populations

eGFR mL/min Max Daily Dose Renal Function Studies

60 2550 mg daily Annually45-59 2000 mg daily Every 3-6 months30-44 1000 mg daily Every 3 months

(don’t startmetformin but can

continue if renal function drops)

< 30 None N/AFood and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. April 8, 2016. http://www.fda.gov/Drugs/DrugSafety/ucm493244.htm

Metformin: Renal Insufficiency• Mortality reduced in patients with chronic renal insufficiency same as for ASCVD

Roussel R, Travert F, Pasquet B, et al. Metformin use and mortality among patients with diabetes and atherothrombosis. Arch Intern Med 2010;170:1892-9.

Metformin + EtOH• EtOH reduces conversion of lactate to glucose

• EtOH reduces hepatic extraction of lactate elevated serum lactate levels

• Avoid acute and chronic excessive intake! (elevated serum lactate levels)

Hulisz DT, Bonfiglio MF, Murray RD. Metformin-associated lactic acidosis. J Am Board Fam Pract 1998;11:233-6.

Metformin: B12 level• Long term use associated with B12 deficiency

• “Periodic measurement of B12 level” especially if anemic or peripheral neuropathy (Level B)

• Up to 1 in 14 patients develop B12 deficiency after 4 years

J Clin Endocrinol Metab 2016;101:1754. BMJ 2010;340:c2181.

Screen: B12 Deficiency

• Don’t routinely screen!• Definitely screen if neuropathy or macrocytic anemia present!

• Definitely screen every 2-3 years for “at risk” metformin users


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WHO is at risk for a B12 Deficiency?• Vegetarians, • PPI users, H2 blockers, INH,

colchicine• “Elderly” • Gastric bypass • Ileal resection, etc.• Atrophic gastritis, achlorhydria


Symptoms of B12 Deficiency

• Weakness, fatigue, loss of appetite, weight loss

• Difficulty with balance, numbness, tingling hands, feet

• Memory problems

Vitamin B12 fact sheet for health professionals. National Institutes of Health office of dietary supplements website: https://ods.od.nih.gov/factsheets/VitaminB12-HealthProfessional/#h3. (Accessed Jan 7, 2018).

B12 Deficiency Present• Do NOT stop metformin!• Benefits of metformin outweigh risks

• Mild to moderate deficiency: Treat with 1000-2000 mcg/day or oral/ sublingual B12 ($4/month), Intranasal ($400/month) (Level A)

• Severe Deficiency/Neuro symptoms present: Injectable B12


B12 Deficiency Present• OTC B12 should include “USP verified” symbol

• Avoid OTC non-FDA approved oral inhalation formulations (e.g., VitaminVape B12) until safety and efficacy data are available

PL Detail-Document, Management of Vitamin B12 Deficiency. Pharmacist’s Letter/Prescriber’s Letter. May 2016.

Metformin Summary• Preferred INITIAL agent (Level A)• Effective, safe, inexpensive (generic)

• May reduce CV mortality in obese patients; reduce CV events

So, when metformin doesn’t get A1C to goal…..• Add a second agent• Which one?• What’s the most important question to ask yourself?

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…..the question is…• Does the patient have ASCVD?

• If no: any of 6 classes: SU, TZD, DPP-4 inh, SGLT2, GLP-1 receptor agonist, basal insulin

• If yes: add agent proven to reduce major adverse CV events and/or CV mortality

Sulfonylureas

• Discovered in 1942!• Sulfonamide antibiotics research

• Found that sulfonylureas induced hypoglycemia in animals

Patlak M (Dec 2002). "New weapons to combat an ancient disease: treating diabetes". FASEB Journal. 16 (14): 1853. doi:10.1096/fj.02-0974bkt. PMID 12468446.

Sulfonylureas• Stimulate pancreatic insulin secretion

• Generic• Good choice if you’re still able to produce insulin (when is that?)

• Loses efficacy over time


Sulfonylureas• Cause an “insulin surge”• What 2 side effects do we see most often?

• Why?


Sulfonylureas• Decrease A1C 1-2%• Cost is about $10/month


Sulfonylureas• First Generations: avoid prescribing related to hypoglycemia

• Second Generations: preferred

Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203.

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SulfonylureasFirst Gens (NOT preferred)•Chlorpropamide (Diabinese, generics)

•Tolazamide (Tolinase, generics)

•Tolbutamide (Orinase, generics)Clinical Pharmacology [database online]. Tampa, FL: Gold Standard, Inc.; 2017. http://www.clinicalpharmacology.com. (Accessed January 6, 2018).

SulfonylureasFirst Gens (NOT preferred)

• Tolbutamide (Orinase, generics)

• Increased CV mortality warnings with tolbutamide

• Is this a class effect? Specific to First Gen agents?


SulfonylureasSecond Gens (Preferred)• Glyburide (Diabeta, Glynase, Micronase,

generics, with metformin [Glucovance])

• Glipizide (Glucotrol, Glucotrol XL, generics, with metformin [Metaglip])

• Glimepiride (Amaryl, generics, with metformin [Amaryl M], with pioglitazone [Duetact], with rosiglitazone [Avandaryl])


2nd Gen Sulfonylureas

Which ones are preferred?Glyburide, Glipizide

preferred over Glimepiride

WHY?Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203.

2nd Gen SulfonylureasWhich ones are preferred?• Less hypoglycemia (especially with renal dysfunction) Less with glimepiride versus glyburide

• Less weight gain with glipizide and glimepiride versus glyburide

Nathan DM, Buse JB, Davidson MB, et al. Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2009;32:193-203.

Cost of Sulfonylureas• Glimepiride

8 mg (less than $10)

• Glipizide IR40 mg (doses>30 mg should be divided BID) (less than $10)

• Glipizide XL20 mg (less than $10)

• Glyburide20 mg (standard; doses>10 mg can divide BID);12 mg (micronized product; once daily or in divided doses) (~$11)

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Tips for Prescribing Sulfonylureas• OK to continue SU with basal insulin• Stop SU if mealtime insulin started (too

much weight gain, too expensive)

• Renal patients: Glyburide NOT recommended

• Renal patients: Conservative in prescribing glipizide and glimepiride to prevent hypoglycemia; ADA says “avoid”

Diabetes Care 2018 Jan; 41(Supplement 1): S73-S85. https://doi.org/10.2337/dc18-S008

SU Summary• Effective, safe, inexpensive (generic)

• Use 2nd gen agents, avoid 1st gen• ASCVD neutral• Weight gain• Hypoglycemia risk

Thiazolidinediones(TZDs)• Introduced in the late 1990s • Increases insulin sensitivity in muscle and fat

• Generic• Pioglitazone (Actos)• Rosiglitazone (Avandia)

American Diabetes Association. Standards of medical care in diabetes –2017. https://professional.diabetes.org/sites/professional.diabetes.org/files/media/dc_40_s1_final.pdf. (Accessed December 1, 2017).

TZDs: Experimental, failed and non-marketed agents:

1. Ciglitazone2. Darglitazone3. Englitazone4. Netoglitazone5. Rivoglitazone6. Troglitazone (Rezulin), which was

withdrawn from the market due to an increased incidence of drug-induced hepatitis.

7. Balaglitazone (DRF-2593)

TZDs• Low risk of hypoglycemia when used as monotherapy

• May stabilize atherosclerotic plaques in the carotid arteries

• Pioglitazone 45 mg/d for NASH patients (with or without DM) reduces steatosis, inflammation, fibrosis


TZD Risks• Edema • Weight gain• Heart failure• Increased fracture risk• Increased LDL (rosiglitazone)• Possible increased risk of bladder cancer (pioglitazone). Assess risk factors and counsel patients to report hematuria


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TZDs: Renal Considerations

• NO renal dosing needed but generally avoided due to fluid retention


TZDs• Glycemic control better sustained over diabetes course than metformin or sulfonylureas

• Pioglitazone may improve lipid profile (e.g., lowers triglycerides)

21American Diabetes Association. Standards of medical care in diabetes –2017. https://professional.diabetes.org/sites/professional.diabetes.org/files/media/dc_40_s1_final.pdf. (Accessed December 16, 2017).

TZDs: CV Benefit

• Pioglitazone use for about three years in patients with type 2 diabetes and macrovascular disease may reduce the risk of all-cause mortality, nonfatal MI and stroke (NNT = 50)

[Evidence level A; high-quality RCT]

Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomisedcontrolled trial. Lancet 2005;366:1279-89.

TZDs: CV Benefit• Pioglitazone: The IRIS trial found use of pioglitazone for about five years in patients with prediabetes and a history of stroke (with mild impairment) or transient ischemic attack may reduce the risk of a future stroke or MI (NNT = 36)

[Evidence level A; high-quality RCT]Kernan WN, Viscoli CM, Furie KL, et al. Pioglitazone after ischemic stroke or transient ischemic attack. New Engl J Med 2016;374:1321-31.

TZDs: CV Benefit

• Subgroup analysis found use of pioglitazone for about three years in patients with type 2 diabetes and a previous stroke may reduce the risk of recurrent fatal or nonfatal stroke (NNT = 22)

• [Evidence level A; high quality RCT].

Wilcox R, Bousser MG, Betteridge OJ, et al. Effects of pioglitazone in patients with type 2 diabetes with or without previous stroke: results from PROactive (PROspective pioglitAzone Clinical Trial In macroVascularEvents 04). Stroke2007;38:865-73.

Cost of TZDs

• Rosiglitazone: 8 mg ($325)• Pioglitazone: 45 mg ($14)

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TZD Summary• Effective, inexpensive (generic)

• Possible CV benefit: pioglitazone

• Risk of bone fractures• HF warning• Weight gain• No hypoglycemia

The 3 Generic Medications

• Metformin• Sulfonylureas• TZDs

….and we agreed to start with METFORMINBut when a second agent was needed, the question to ask is…..

Is ASCVD present?

• If no, any of 6 classes: SU, TZD, DPP-4 inh, SGLT2, GLP-1 receptor agonist, basal insulin

• If yes: “add agent proven to reduce major adverse CV events and/or CV mortality”

Pharmacologic Approaches to Glycemic Treatment: Standards of Medical Care in Diabetes - 2018. Diabetes Care 2018.

SGLT-2 Inhibitor90% glucose blocked by inhibiting SGLT-2

SGLT-2 carries 90% of renal glucose (proximal tubule)

SGLT-1 carries 10% of renal glucose (distal tubule)

90% of glucose passes thru the nephron, ureters, then out the urine

A consequence of dumping glucose….•Glucose is a carbohydrate…..

•Provides 4 calories/gram•If 50-100 grams of glucose are dumped in the urine daily

•Hhhmmmmm……..

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Another consequence of dumping glucose….50-100 x 4 = 200-400 calories/day •Loss of 200-400 calories daily•3600 calories = 1 pound•9-18 days result in 1 lost pound•6 months 4-7 lb. weight loss

SGLT-2 InhibitorsSodium-glucose co-transporter 2 (SGLT2) inhibitors or “flozins”

• Canagliflozin (Invokana)

• Dapagliflozin (Farxiga)

• Empagliflozin (Jardiance)

• Ertugliflozin (Steglatro)


SGLT-2 Inhibitors•Canagliflozin300 mg (~$465)

•Dapagliflozin10 mg (~$465)

•Empagliflozin25 mg (~$465)

•Ertugliflozin15 mg (~$270)

Clinical Resource, Drugs for Type 2 Diabetes. Pharmacist’s Letter/Prescriber’s Letter. July 2017.

SGLT-2 Inhibitors

When is the best time of day to take?

SGLT-2 Inhibitors• Decrease A1C 0.7% to 1%• Hypoglycemia rare• Weight loss


SGLT-2 InhibitorsCV benefit: empagliflozin use in patients with CVD for about 3 years may reduce: (Evidence level A)

• Hospitalizations due to heart failure (NNT = 71)

• CV death (NNT = 45); 38% reduction!

• Overall death (NNT = 39)

• Empagliflozin use has NOT been shown to reduce individual rates of MI or stroke

Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.

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SGLT-2 InhibitorsCV benefit: CANVAS (CANagliflozincardioVascular Assessment Study)

(Evidence level A)

• Use for about 3.5 years when added to standard glucose-lowering therapy in patients with type 2 diabetes and very high CV risk (>70% of patients had atherosclerotic CV disease):

• May reduce the combined endpoint of CV mortality

• Nonfatal MI

Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017 June 12. Doi: 10.1056/NEJMoa1611925.

SGLT-2 InhibitorsCV benefit: CANVAS (CANagliflozincardioVascular Assessment Study)

(Evidence level A)

•Nonfatal stroke (NNT=333). However, when evaluated individually, these endpoints were no longer significantly reduced.

Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017 June 12. Doi: 10.1056/NEJMoa1611925.

Why Cardiovascular Benefits?

• Empagliflozin (Jardiance)• Reduced CV mortality in T2DM patients at high risk of vascular events

• Why? Plasma volume? Hctincreased from 48.9% to 51.8%

EMPA-REG OUTCOME study, Diabetes Care (2018;41:356-363)

SGLT-2 Inhibitors• Dizziness, hypotension

• Increase LDL 4-8 mg/dL

American Diabetes Association. Standards of medical care in diabetes –2017. https://professional.diabetes.org/sites/professional.diabetes.org/files/media/dc_40_s1_final.pdf. (Accessed December 21, 2017.)

SGLT-2 Inhibitors• Fractures (rare, in susceptible patients)

• Decrease in BMD (canagliflozin)

Hackethal V. SGLT2 inhibitors and fracture risk: a review of what we know. Endocrinology Network, March 30, 2015. http://www.endocrinologynetwork.com/sglt2/sglt2-inhibitors-and-fracture-risk-review-what-we-know. (Accessed June 5, 2017).

FDA. Invokana and Invokamet (canagliflozin): drug safety communication – new information on bone fracture risk and decreased bone mineral density. September 10, 2015.

SGLT-2 InhibitorsRenal• May be associated with increased risk of bladder cancer (dapagliflozin)

• Acute kidney injury, may require dialysis (canagliflozin, dapagliflozin)

• Hyperkalemia, especially in patients with renal impairment

Product information for Farxiga. Merck Sharp&Dohme. Subsidiary of Merck. Whitehouse, NJ 08889. December 2017.FDA. FDA drug safety communication. FDA confirms increased risk of leg and foot amputations with the diabetes medication canagliflozin (Invokana, Invokamet, InvokametXR). May 16, 2017.

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SGLT-2 InhibitorsRenal Benefit (preserved renal function)

• Canagliflozin• Empagliflozin


SGLT-2 Inhibitors: eGFRDo not use if: • eGFR< 45 mL/min/1.73m2

(canagliflozin, empagliflozin) • eGFR< 60 mL/min/1.73m2

(dapagliflozin, ertugliflozin)


SGLT-2 InhibitorsAmputations• Amputations may occur in about 6 of every 1,000 patients treated with canagliflozin over one year, compared to about 3 in every 1,000 patients on other diabetes meds

• Be careful using any flozin if high risk of amputation due to neuropathy, PVD, foot ulcers

FDA. FDA drug safety communication. FDA confirms increased risk of leg and foot amputations with the diabetes medication canagliflozin (Invokana, Invokamet, InvokametXR). May 16, 2017.

SGLT-2 Inhibitors

Amputations• Canagliflozin use in patients at high CV risk for about 3.5 years may increase risk of amputations, NNH ~77 (Evidence level A)

Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med 2017 June 12.

SGLT-2 InhibitorsKetoacidosis • What are risk factors for ketoacidosis?

SGLT-2 Summary• CV benefit: canagliflozin, empagliflozin

• High cost• Weight loss• No hypoglycemia• DKA risk• Hypotension• Risk of amputation, fractures: canagliflozin

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DPP-4 InhibitorsMechanism of Action• Increases insulin secretion in response to elevated blood glucose

• Decreases glucagon secretion • Increases sense of fullness • Slows gastric emptying


DPP-4 Inhibitors• Alogliptin (Nesina)

25 mg (~$195)• Linagliptin (Tradjenta)

5 mg (~$380)

• Saxagliptin (Onglyza)5 mg (~$385)

• Sitagliptin (Januvia)100 mg (~$380)


DPP-4 Inhibitors• May be associated with pancreatitis

• New or worsening HF (saxagliptin and alogliptin) Evidence level A

• May cause severe joint pain• Low risk of hypoglycemia when used as

monotherapy


1.Scirica BM, Bhatt DL, Braunwald E, et al. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317-26.2.Zannad F, Cannon CP, Cushman WC, et al. Heart failure and mortality outcomes in patients with type 2 diabetes taking alogliptin versus placebo in EXAMINE: a multicentre, randomised, double-blind trial. Lancet 2015;385:2067-76.

DPP-4 Inhibitors• Dosage modification with renal

impairment needed (sitagliptin, saxagliptin, alogliptin)

• CYP3A4 interactions (saxagliptin, linagliptin)

• Reduces postprandial glucose

• Weight neutral

• Generally well tolerated


DPP-4 Inhibitors• ASCVD Neutral• Potential risk: saxagliptin, alogliptin


DPP-4 Inhibitor Summary• Pancreatitis risk• HF risk (saxagliptin and alogliptin)

• May cause severe joint pain• Low risk of hypoglycemia• ASCVD neutral

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Dual Therapy: Metformin Plus

Metformin plusSulfonylurea

Metformin plusTZD

Metformin plusDPP4

Metformin plusSGLT2

Metformin plusGLP-1

Efficacy High High Intermediate Intermediate High

Hypoglycemia Risk

Moderate Low Low Low Low

Weight gain Gain Gain Neutral Loss Loss

Side Effects Hypoglycemia

Edema, HF, fxs

Rare GU, dehydration

GI

Costs Low Low High High High

Adapted from Diabetes Care volume 39, supp 1, January 2016

Add an Agent with CV Benefit

• Metformin: potential benefit• SGLT-2 Inhibitors: canigloflozin, empagliflozin

• TZD: potential benefit pioglitazone

Avoid Agents with detrimental effects if patient is at high risk!

• Lactic acidosis: metformin • Amputations: canagliflozin• HF: TZDs, saxagliptin and alogliptin

• Bone loss: SGLT-2, TZDs• Hypoglycemia: SU

Thank you!For questions or to contact me:

Amelie Hollier, DNP, FNP-BC, FAANP

[email protected]

Advanced Practice Education AssociatesLafayette, LA

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