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What's New in Type 2: A look at newer agents and glycemic management in older adults

Daphne Schneider, MD, CAQCambridge Health AllianceDivision of Geriatrics

Garrett Lech, PharmD, BCACPClinical Pharmacist SpecialistCambridge Health Alliance

Disclosures

There are no relevant financial relationships with any commercial interests to disclose.

Objectives

• Discuss newer agents available for the treatment of diabetes mellitus and their place in therapeutic regimens

• Describe specific considerations for determining glycemic targets and treatment options in older adults with Type 2 Diabetes Mellitus (T2DM)

• Recognize common and severe adverse drug reactions of DPP-IV inhibitors, SGLT-2 inhibitors, and GLP-1 receptor agonists

• Design a pharmacologic treatment plan for older patients with T2DM

Our Model

• Cambridge Health Alliance is a public hospital caring for more than 140,000 patients annually

– 3 hospitals– 12 primary care centers– Elder Service Plan

• Safety net provider serving highest concentration of Medicaid patients in the state

• Pharmacotherapists integrated into primary care clinics to co-manage

– diabetes– hypertension– hyperlipidemia– anticoagulation– smoking cessation– COPD– asthma– pain– travel medicine– complex medication regimens

Epidemiology

• More than 30 million Americans have diabetes (9.4% of the population)

• More than 20% of persons age 65 years and older are diagnosed with diabetes

• The largest % increase in diabetes prevalence in any age group will be among those >75 years of age

• Older adults with diabetes have a 10-year reduction in life expectancy and mortality rate twice that of people without diabetes

Centers for Disease Control and Prevention. National Diabetes Statistics Report [Internet], 2017.Narayan, K.M. Venkat, et al. Diabetes Care, American Diabetes Association, 1 Sept. 2006“Diabetes in the UK 2010: Key Statistics on Diabetes.” Diabetes.org.uk, Diabetes UK, Mar. 2010, Diabetes in the UK 2010: Key statistics on diabetes.

Patient Case -- DS

• 66 yo Caucasian male• PMH

– T2DM (complicated by microalbuminuria)

– HTN– Recurrent angioedema– Chronic low back pain– HLD– OA– Caregiver stress

• Labs– A1c 8.2%– UACR 114mcg/mg– LDL 58– SCr 1.1 (eGFR

>60mL/min)– BP 114/66 mmHg

• Medications– Metformin 1000mg twice

daily– Losartan 100mg daily– ASA 81mg daily– Amlodipine 5mg daily– Atorvastatin 20mg daily– Fexofenadine 180mg daily

Where do we go from here?

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Pathophysiology

1

23

45

67

8

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

Treatment Algorithms

• Many treatment algorithms/guidelines• 1st line - metformin• 2nd line - PATIENT-SPECIFIC• Factors to consider

– patient preference– current A1c– hypoglycemia risk– co-morbidities/functional status– socioeconomic factors

Riddle MC et al. Diab Care. 2019; 42(1).

Patient Case - CG

• 88 yo female (2014) living in ALF

• DM >40 yrs• PVD, HTN, HLD, spinal

stenosis, dementia, obesity• eGFR>60mL/min• “brittle diabetes” w/ h/o

nocturnal hypoglycemia (BGs in 30mg/dL)

• NPH/regular mix 70/30 - twice daily (20 units + 8 units)

• acarbose 25mg TID– A1c 8.9% without home

monitoring– no hypoglycemia

• 2014 - hospitalized for GI bleed → sent to SNF x3 months– SNF concern - lack of DM

control without basal-bolus insulin regimen

– Family/patient preference - return to ALF (where basal-bolus not possible)

SO WHAT DO WE DO??

Who is an Older Adult?

considerations in older adults

Melanie J. Davies et al. Dia Care 2018;41:2669-2701

Increased Prevalence of DM in Elders May Be Due to

• Decreased activity >> impairment in insulin action

• Age-associated decline in pancreatic B cell function

• Age related decline in insulin signaling mechanisms that limits mobilization of glucose transporters necessary for insulin mediated glucose uptake

• Increased visceral fat >> insulin resistance

Kalyani RR et al. Diabetes Care. 2017 Apr; 40:440-443

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Limitations of A1c Measurement

• A1c is less reliable in anemia, ESRD especially with erythropoietin therapy due to changes in RBC turnover

• Post transfusion A1c is not a meaningful representation of true mean glycemia

Kirkman MS et al; Diab Care. 2012 Dec;35(12):2650-64

Individualizing DM Care for Elders

• Assess goals and preferences

• Assess patient longevity and functional status• Consider time needed for treatment impact

– It takes 8 years to see benefits of glycemic control– It takes 2-3 years to see benefits from blood

pressure/lipid control• No evidence that intensive hyperglycemia

management (A1c ≤ 6.5%) prevents CVD in older adults with established diabetes

• Greater hypoglycemia/hypoglycemia unawareness

Kirkman MS et al; Diab Care. 2012 Dec;35(12):2650-64

Framework for Treatment Goals in Older Adults with Diabetes

Patient Characteristics/ Health Status

Rationale Reasonable A1c Goal*

Fasting or Pre-prandial Glucose (mg/dL)

Bedtime Glucose (mg/dL)

Blood Pressure (mmHg)

Lipids

Healthy (few existing chronic illnesses, intact cognitive and functional status)

longer remaining life expectancy

<7.5% 90-130 90-150 <140/80 statin unless contraindicated or not tolerated

Complex/intermediate (multiple coexisting chronic illnesses or 2+ instrumental ADL impairments or mild-moderate cognitive impairment

intermediate remaining life expectancy, high treatment burden, hypoglycemia vulnerability, fall risk

<8.0% 90-150 100-180 <140/80 statin unless contraindicated or not tolerated

Very complex/poor health (long-term care or end-stage chronic illnesses or moderate to severe cognitive impairment or 2+ ADL dependencies

lim ited remaining life expectancy makes benefit uncertain

<8.5% 100-180 110-200 <150/90 consider likelihood of benefit w ith statin (secondary prevention more so than primary)

Kirkman MS et al; Diab Care. 2012 Dec;35(12):2650-64

Non-insulin Agents

Melanie J. Davies et al. Dia Care 2018;41:2669-2701 Riddle MC et al. Diab Care. 2019; 42(1): 102.

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Blood Glucose Targets by Class

Drug class Primary Target FPG vs PPG A1c Lowering

Biguanide hepatic glucose FPG 1 - 2%

Sulfonylurea insulin secretion FPG and PPG 1 - 2%

DPP-IV inhibitor incretin effect PPG 0.5 - 1%

SGLT-2 inhibitor glucose reabsorption FPG and PPG 0.7 - 1%

GLP-1 agonist incretin effect FPG and PPG 1.5%

TZD glucose uptake FPG and PPG 0.5 - 1.5%

Meglitinides insulin secretion PPG 0.5 - 1%

Alpha-glucosidase inhibitor glucose absorption PPG 0.3 - 0.8%

TZD: ThiazolidinedioneFPG: fasting plasma glucosePPG: prandial plasma glucose

Metformin

• 2016 FDA label change for dosing considerations based on eGFR

Inzucchi et al. JAMA. 2014;312(24):2668-2675FDA Drug Safety Communication: FDA Revises Warnings Regarding Use of the Diabetes Medicine Metformin in Certain Patients with Reduced Kidney Function.” S Food and Drug Administration Drug Safety and Availability Page, 8 Apr. 2016.

• DPP - metformin (44% younger pts vs 11% older pts); lifestyle (48% younger pts vs 71% older pts)

Patient Case -- DS

• 66 yo Caucasian male• PMH

– T2DM (complicated by microalbuminuria)

– HTN– Recurrent angioedema– Chronic low back pain– HLD– OA– Caregiver stress

• Labs– A1c 8.2%– UACR 114mcg/mg– LDL 58– SCr 1.1 (eGFR

>60mL/min)– BP 114/66 mmHg

• Medications– Metformin 1000mg twice

daily– Losartan 100mg daily– ASA 81mg daily– Amlodipine 5mg daily– Atorvastatin 20mg daily– Fexofenadine 180mg daily

Pt actively trying to lose weight and increase activity throughout year

Pt prefers to avoid injectable agents if possible

Now, where do we go?

DS -- DPP-IV Inhibitor

Initiated sitagliptin 100mg daily

● Current regimen is metformin XR 500mg - 4 tablets daily (switched from IR d/t some adherence concerns) and sitagliptin 100mg daily

● Minimal effect of weight since beginning sitagliptin -- 241lbs (2/6/18) → 235lbs (1/2019)

Incretin Mimetics

• The Incretin Effect

Image: http://tmedweb.tulane.edu/pharmwiki/doku.php/incretins_diabetes

Holst, J. J., and C. Orskov. Diabetes, vol. 53, no. Supplement 3, 2004,

DPP-IV Inhibitors (“-gliptins”)

Drug Brand Frequency Dose Adjustments

sitagliptin Januvia Daily eGFR<45ml/min

saxagliptin Onglyza Daily eGFR<45mL/min

linagliptin Tradjenta Daily None

alogliptin* Nesina Daily CrCl<60mL/min

● All agents are oral● Minimal side effects● Weight neutral

*Generic available

Januvia (sitagliptin) [prescribing information]. Kenilworth, NJ: Merck&Co; January 2019.Onglyza (saxagliptin) [prescribing information]. Cambridge, United Kingdom: AstraZeneca; January 2019.Tradjenta (linagliptin) [prescribing information]. Ingelheim an Rhein, Germany: Boehringer Ingelheim; January 2019.Nesina (alogliptin) [prescribing information]. Osaka, Japan: Takeda Pharmaceuticals; January 2019.

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DPP-IV Inhibitors: Mechanism of Action

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

DPP-IV Inhibitors

- Joint pain- 2015 FDA warning: 33 cases (severe arthralgia, myalgias, muscle weakness)- 33 cases of severe arthralgia, myalgias, muscle weakness have been reported in the

post-marketing period 2006 - 2013

- Acute pancreatitis- Animal studies- Singh et al -- 2013 observational study

- ~ twice the risk of hospitalization for acute pancreatitis (exenatide)- No other observational studies to date have been able to find a link between

GLP-1-based therapies and pancreatitis

- Insurance coverage- MassHealth - preferred excluding alogliptin (PA/ST)- Medicare - Tier 2-3: most robust for sitagliptin and linagliptin

Lowes, Robert. Medscape, 28 Aug. 2015.Devaraj, S., and A. Maitra. Diabetes, vol. 63, no. 7, 2014, pp. 2219–2221.Hans DeVries J. et al. Diabetes Care, 40:161-163, 2017.Commonwealth of Massachusetts Antidiabetic Agents-Oral, Health and Human Services, Dec. 2018.“Formulary Lookup.” Formulary Lookup, Managed Markets Insight & Technology, LLC, 2019, formularylookup.com/.

Patient Case -- JY

• 80 yo Chinese male• PMH

– T2DM (w/ CKD 3)– HLD– HTN– Dementia– h/o falls– Osteopenia– BPH

• Labs– A1c 9.1%– UACR 137mcg/mg– LDL 104mg/dL– SCr 1.2 (eGFR 58mL/min)– BP 160/80 mmHg (typical

120s/70-80)

• Medications– Insulin glargine 52 units daily– Metformin XR 1000mg daily– Sitagliptin 50mg daily– Pravastatin 40mg daily– ASA 81mg daily– Tamsulosin 0.4mg daily

• Previously trialed: Novolog mix 70/30 (stopped d/t difficulty with twice daily injection)

What antidiabetic agent(s) can we consider here?

JY - GLP-1 Agonist

Initiated dulaglutide0.75mg weekly (2/28/18)

● Avg BG pre-dulaglutide 254mg/dL

● Avg BG post-dulaglutide 129mg/dL

Poor appetite and recent admission for sepsis

Pt/pt’s daughter noted overeating greatly reduced with dulaglutide and continue to this day. Ease of a once weekly injection for family in patient with dementia.

Currently on metformin XR 1000mg daily, insulin glargine 40 units daily, and dulaglutide 0.75mg weekly

GLP-1 Receptor Agonists (“-tides”)

Drug Brand Frequency Renal Contraindications

exenatideByetta BID

CrCl<30mL/min

Bydureon Weekly

liraglutide Victoza Daily None

albiglutide Tanzeum Weekly None

dulaglutide Trulicity Weekly None

lixisenatide Adlyxin Daily eGFR<15mL/min

semaglutide Ozempic Weekly None

● All agents are injectable● ADR: GI upset, N/V● Weight loss

Byetta (exenatide) [prescribing information]. Cambridge, United Kingdom: AstraZeneca; January 2019.Bydureon (exenatide) [prescribing information]. Indianapolis, IN. AstraZeneca; January 2019.Victoza (liraglutide) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January 2019.

Tanzeum (albiglutide) [prescribing information]. Brentford,United Kingdom: GlaxoSmithKline; January 2019.Trulicity (dulaglutide) [prescribing information]. Cambridge, United Kingdom: Lilly, LLC; January 2019.

Adlyxin (lixisenatide) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US, LLC; January 2019.Ozempic (semaglutide) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January 2019.

GLP-1 RA: Mechanism of Action

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

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GLP-1 Agonists

• Thyroid cancer– Endogenous GLP and RAs stimulate thyroid GLP-1 receptors →

increased calcitonin release/increased c-cell proliferation– Increased risk of c-cell carcinomas and adenomas in rodents exposed to

exenatide, liraglutide, dulaglutide– Human post-marketing -- MTC with liraglutide (5) and dulaglutide (1)– Seem to be dose and treatment duration dependent– Thyroid nodules are NOT a contraindication, but should be monitored

• Insurance coverage– MassHealth - exenatide immediate release preferred. Others PA/ST– Medicare - Tier 2-3: robust coverage excluding exenatide immediate

release

Victoza (liraglutide) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January 2019.Trulicity (dulaglutide) [prescribing information]. Cambridge, United Kingdom: Lilly, LLC; January 2019.Nauck, M. A., and N. Friedrich. Diabetes Care, vol. 36, no. Supplement_2, 2013Commonwealth of Massachusetts Antidiabetic Agents-Injectable and Insulin, Health and Human Services, Dec. 2018.“Formulary Lookup.” Formulary Lookup, Managed Markets Insight & Technology, LLC, 2019, formularylookup.com/.

SGLT2 Inhibitors (“-flozins”)

Drug Brand Frequency Renal Considerations

canagliflozin Invokana Daily Adjust eGFR<60mL/min

dapagliflozin Farxiga Daily Not recommended eGFR<60mL/min

empagliflozin Jardiance Daily Not recommended eGFR<45mL/min

ertugliflozin Steglatro Daily Not recommended eGFR<60mL/min

● All agents are oral● ADR: genitourinary infection, hypotension, increased LDL/HDL● Weight loss● Risk/benefit tool Invokana (canagliflozin) [prescribing information]. Beerse, Belgium: Janssen Pharmaceuticals, Inc; January 2019.

Farxiga (dapagliflozin) [prescribing information]. Cambridge, United Kingdom: AstraZeneca; January 2019.Jardiance (empagliflozin) [prescribing information]. Ingelheim an Rhein, Germany: Boehringer Ingelheim; January 2019.Steglatro (ertugliflozin) [prescribing information]. Kenilworth, NJ: Merck&Co; January 2019.Wilding, John, et al. “SGLT2 Inhibitors in Type 2 Diabetes Management: Key Evidence and Implications for Clinical Practice.” Diabetes Therapy, vol. 9, no. 5, 2018, pp. 1757–1773., doi:10.1007/s13300-018-0471-8.

SGLT-2 Inhibitors: Mechanism of Action

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

SGLT-2 Inhibitors• Amputation risk

– 7/2017, FDA warning of canagliflozin-containing drugs– Event rates from CANVAS were 6.3 (cana) vs 3.4 (placebo) per 1000 patient years

(p<0.001)– Post-hoc analysis of EMPA-REG OUTCOME - empagliflozin not associated with increased

risk of lower-limb amputation– 2018 observational cohort study - increased amputation vs other agents (aHR, 2.12; 95%

CI, 1.19-3.77)

• Euglycemic DKA– 2015 - FDA warning (73 reported cases) -- (53/73) provoked

• Fracture risk• Fournier’s Gangrene• Insurance coverage

– MassHealth - preferred excluding ertugliflozin (PA/ST)– Medicare - Tier 2-3: most robust coverage for empagliflozin and dapagliflozin

Glucose excretion → insulin release + glucagon production → lipolysis/ketogenesis

Center for Drug Evaluation and Research. U S Food and Drug Administration Home Page, Center for Drug Evaluation and Research, July 2017.Neal, Bruce, et al. New England Journal of Medicine, vol. 377, no. 7, 2017, pp. 644–657.Chang HS et al. JAMA Intern Med. 2018;(178(9):1190-1198.“FDA Drug Safety Communication” US Food and Drug Administration Drug Safety and Availability Page. 15 May 2015. Rosenstock, Julio, and Ele Ferrannini. Diabetes Care, American Diabetes Association, 1 Sept. 2015.Alba M et al. Curr Med Res Opin. 2016 Aug;32(8):1375-85.“FDA Drug Safety Communication.” US Food and Drug Administration Drug Safety and Availability Page. 29 Aug 2018.Commonwealth of Massachusetts Antidiabetic Agents-Oral, Health and Human Services, Dec. 2018.“Formulary Lookup.” Formulary Lookup, Managed Markets Insight & Technology, LLC, 2019, formularylookup.com/.

Patient Case - RS

61 yo male with a PMH significant for T2DM, HTN, obesity, CHF, s/p MI in 2012. Most recent A1c 8.1%. Based on the evidence from the CVOTs discussed, which agent has the strongest evidence for benefit in this patient?

A. LiraglutideB. EmpagliflozinC. SitagliptinD. Dapagliflozin

Cardiovascular Outcomes Trials (CVOTs)

DPP-IV inhibitors (“-gliptins”)

GLP-1 agonists (“-tides”) SGLT-2 inhibitors (“-flozins”)

sitagliptin TECOS exenatide EXSCEL canagliflozin CANVAS

saxagliptinSAVOR-TIMI

53liraglutide LEADER dapagliflozin

DECLARE-TIMI 58

linagliptinCARMELINA/CAROLINA*

dulaglutide REWIND empagliflozinEMPA-REG OUTCOME

alogliptin EXAMINE albiglutide HARMONY ertugliflozin VERTIS CV

lixisenatide ELIXA

semaglutide SUSTAIN-6

*results for CAROLINA expected 2019

BENEFIT AWAITING FULL RESULTSNEUTRAL AWAITING FULL RESULTS

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Cardiovascular Outcomes Trials (CVOTs)

DPP-IV inhibitors (“-gliptins”)

GLP-1 agonists (“-tides”)

SGLT-2 inhibitors (“-flozins”)

sitagliptin TECOS exenatide EXSCEL canagliflozin CANVAS

saxagliptinSAVOR-TIMI

53liraglutide LEADER dapagliflozin

DECLARE-TIMI 58

linagliptinCARMELINA/CAROLINA*

dulaglutide REWIND empagliflozin EMPA-REG OUTCOME

alogliptin EXAMINE albiglutide HARMONY ertugliflozin VERTIS CV

lixisenatide ELIXA

semaglutide SUSTAIN-6

*results for CAROLINA expected 2019

BENEFIT AWAITING FULL RESULTSNEUTRAL AWAITING FULL RESULTS

LEADER vs EMPA-REG OUTCOME

Trial LEADER EMPA-REG OUTCOME

Number of participants 9340 7020

Characteristics age >50 w/ one CV conditionORage >60 w/ one risk factor

age >18 w/ one CV condition

Mean baseline age (years) 64.3 63.1

Mean baseline A1c (%) 8.7 8.1

Primary Outcome composite death from CV causes, non-fatal MI, non-fatal stroke

composite death from CV causes, non-fatal MI, non-fatal stroke

Median follow up 3.8 years 3.1 years

Marso SP et al. “Liraglutide and cardiovascular outcomes in type 2 diabetes.” NEJM375.4 (2016) 311 – 322.Zinman, Bernard, et al. “Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes —NEJM.” New England Journal of Medicine, 26 Nov. 2015.

LEADER

Marso SP et al. “Liraglutide and cardiovascular outcomes in type 2 diabetes.” NEJM375.4 (2016) 311 – 322.

EMPA-REG OUTCOME

Zinman, Bernard, et al. “Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes —NEJM.”

New England Journal of Medicine, 26 Nov. 2015.

Basal Insulins

72yo female currently taking glargine (Lantus) 75 units every morning, lispro (Humalog) 20 units with meals, metformin 1000mg twice daily, and dulaglutide 0.75mg weekly. Her most recent A1c is 7.8% approximately 2 weeks ago. Her bedtime readings today average 143 and fasting average is 190. She does not snack at bedtime or in the middle of the night. Denies signs and symptoms of hypoglycemia.

What is the most appropriate change to her insulin regimen?

Patient Case - JW

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Insulin

Apr 2000

insulin glargine (Lantus)

Jun 2005

insulin detemir (Levemir)

1950

insulin NPH

1985

1st insulin pen

Feb 2015

Sept 2015

insulin degludec (Tresiba)

insulin glargine (Toujeo)

Dec 2016

insulin glargine (Basaglar)

Humulin N (insulin NPH) [prescribing information]. Indianapolis, IN. Lilly USA, LLC; January 2019.Lantus (insulin glargine) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US, LLC; January 2019.Levemir (insulin detemir) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January 2019.Toujeo (insulin glargine) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US, LLC; January 2019.Tresiba (insulin degludec) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January

Basal InsulinInsulin Novolin/

Humulin NLantus Levemir Toujeo Basaglar Tresiba

Drug name NPH glargine detemir glargine glargine degludec

Duration of action (hours)

14-24 24* 6-23 >24 24* ~42

Peak (hours) 4-12 minimal 3-9 none minimal none

Dosing schedule once-twice daily once daily once-twice daily once daily once daily once daily

Concentration U-100 U-100 U-100 U-300 U-100 U-100; U-200

Devices available Vial, Pen Vial, Pen Vial, Pen Pen Pen Pen

Maximum dose per pen (units)

60 80 80 80160 (max)*

80 U-100: 80U-200: 160*

Beyond use date (days)

31 (vial)14 (pen)

28 pen/vial 42 pen/vial 42 28 56

Median AWP (per 1,000 units)

vial: $165pen: $377

vial: $323pen: $323

vial: $353pen: $353

pen: $331max pen: $331

pen: $261 u-100: $388u-200: $388

*may last 10.8->24 hrs Humulin N (insulin NPH) [prescribing information]. Indianapolis, IN. Lilly USA, LLC; January 2019.Lantus (insulin glargine) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US, LLC; January 2019.Levemir (insulin detemir) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January 2019.Toujeo (insulin glargine) [prescribing information]. Bridgewater, NJ: Sanofi-Aventis US, LLC; January 2019.Tresiba (insulin degludec) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January 2019.

Insulin glargine u-100 vs insulin glargine u-300

Hypoglycemia with Basal Insulin

Insulin glargine vs insulin degludec– No difference in overall hypoglycemia

risk in pre-approval trials– Less nocturnal hypoglycemia– Meta-analysis of 5 Phase 3a trials

(BEGIN series) lower rates of all hypoglycemia, including nocturnal hypoglycemia with degludec

Riddle MC et al. Diabetes Care, American Diabetes Association, 1 Oct. 2014.Rodbard H, et al. Endocrine Practice: April 2014. 4; 285-292.

Simplification of Complex Insulin Regimen

Lorem Ipsum

Lorem IpsumLorem Ipsum

Lorem Ipsum Lorem Ipsum Lorem Ipsum

Basal and/or mealtime insulins

Mealtime insulinBasal insulin

Change timing from bedtime to

morning

If >10 units/dose: -50% and add non-

insulin agent

If <10 units/dose: d/c and add non-

insulin agent

Titrate dose based on fasting blood glucose

Fasting goal: 90-150mg/dL Taper mealtime insulin as titrating noninsulin agent doses

with goal of d/c

Add non-insulin agents:metformin with eGFR

>45mL/min

If 50% of fasting blood glucose values are over the goal: +2 units.

If >2 values are <80mg/dL: -2 units Use patient and drug characteristics to guide decision making as needed:

Goal 90-150mg/dL pre-mealsIf 50% >goal: increase dose or add agent

If >2 pre-meal values <90mg/dL: decrease dose

Premixed insulin

70% total dose as basal only

Riddle MC et al. Diab Care. 2019;42(1):S139-S147

Summary

• Older adults have largest growing prevalence of T2DM

• Consider factors such as cognitive/functional status, comorbidities, and patient preference when determining glycemic targets

• Avoid hypoglycemia

• If using complex insulin regimens, consider simplification

• Start low, go slow...BUT GO!

References1. Centers for Disease Control and Prevention. National Diabetes Statistics Report [Internet], 2017. Available from

https://www.cdc.gov/diabetes/data/statistics/statistics-report.html. Accessed 29 January 20192. Narayan, K.M. Venkat, et al. “Impact of Recent Increase in Incidence on Future Diabetes Burden.” Diabetes Care, American Diabetes Association, 1 Sept.

2006, care.diabetesjournals.org/content/29/9/2114.3. “Diabetes in the UK 2010: Key Statistics on Diabetes.” Diabetes.org.uk, Diabetes UK, Mar. 2010, Diabetes in the UK 2010: Key statistics on diabetes.4. DeFronzo RA. Diabetes. 2009;58:773-795.5. Riddle MC et al.“Standards of Medical Care in Diabetes--2017.” Diabetes Care. 42(1)..6. Melanie J. Davies et al. Diabetes Care 2018;41:2669-27017. Riddle MC et al. “Standards of Medical Care in Diabetes-2019. Diabetes Care. 2019; 42(1): 102.8. Kalyani RR et al. “Diabetes and Aging: Unique Considerations and Goals of Care.” Diabetes Care. 2017 Apr; 40:440-4439. Kirkman MS et al. “Diabetes in Older Adults: A Consensus Report.” Diabetes Care. 2012 Dec;35(12):2650-6410. Inzucchi et al. “Metformin in Patients with Type 2 Diabetes and Kidney Disease: A Systematic Review.” JAMA. 2014;312(24):2668-267511. “FDA Drug Safety Communication: FDA Revises Warnings Regarding Use of the Diabetes Medicine Metformin in Certain Patients with Reduced Kidney

Function.” US Food and Drug Administration Drug Safety and Availability Page, 8 Apr. 2016, www.fda.gov/Drugs/DrugSafety/ucm493244.htm.12. Holst, J. J., and C. Orskov. “The Incretin Approach for Diabetes Treatment: Modulation of Islet Hormone Release by GLP-1 Agonism.” Diabetes, vol. 53, no.

Supplement 3, 2004, doi:10.2337/diabetes.53.suppl_3.s197.13. Januvia (sitagliptin) [prescribing information]. Kenilworth, NJ: Merck&Co; January 2019.14. Onglyza (saxagliptin) [prescribing information]. Cambridge, United Kingdom: AstraZeneca; January 2019.15. Tradjenta (linagliptin) [prescribing information]. Ingelheim an Rhein, Germany: Boehringer Ingelheim; January 2019.16. Nesina (alogliptin) [prescribing information]. Osaka, Japan: Takeda Pharmaceuticals; January 2019.17. Lowes, Robert. “DPP-4 Inhibitors for Diabetes Can Cause Severe Joint Pain, FDA Says.”Medscape, 28 Aug. 2015, www.medscape.com/viewarticle/850231.18. Devaraj, S., and A. Maitra. “Pancreatic Safety of Newer Incretin-Based Therapies: Are the "-Tides’ Finally Turning?” Diabetes, vol. 63, no. 7, 2014, pp. 2219–

2221., doi:10.2337/db14-0545.19. Hans DeVries J. et al. “DPP-4 Inhibitor - Related Pancreatitis: Rare but Real!” Diabetes Care, 40:161-163, 2017.20. Azoulay, Laurent, et al. “Incretin Based Drugs and the Risk of Pancreatic Cancer: International Multicentre Cohort Study.” BMJ, British Medical Journal

Publishing Group, 17 Feb. 2016, www.bmj.com/content/352/bmj.i581.21. Commonwealth of Massachusetts Antidiabetic Agents-Oral, Health and Human Services, Dec. 2018,

masshealthdruglist.ehs.state.ma.us/MHDL/pubtheradetail.do?id=26.22. “Formulary Lookup.” Formulary Lookup, Managed Markets Insight & Technology, LLC, 2019, formularylookup.com/.23. Byetta (exenatide) [prescribing information]. Cambridge, United Kingdom: AstraZeneca; January 2019.24. Bydureon (exenatide) [prescribing information]. Indianapolis, IN. AstraZeneca; January 2019.25. Victoza (liraglutide) [prescribing information]. Bagsvaerd, Denmark: Novo Nordisk Inc; January 2019.

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