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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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