Download presentation
Presentation is loading. Please wait.
Published byCurtis Montgomery Modified over 8 years ago
1
Diabetes Update 2016: New Drugs and New Methods of Care Kelly Murray, PharmD, BCACP Clinical Assistant Professor of Clinical Pharmacy OSU College of Osteopathic Medicine Emergency Department Clinical Pharmacist OSU Medical Center
2
Overview Standards of Care 2016 Updates New Diabetes Therapies Oral medications Injectable medications Insulin therapies Innovative Care Solutions and Ideas 2
3
Objectives Describe the mechanisms of action of the newest type 2 diabetes medications – DPP4-inhibitors, incretin mimetics, and SGLT-2 inhibitors. Recall advantages of insulin degludec over insulin glargine. List 3 resources to assist patients with the costs of their medications. 3
4
Standards of Care 2016 Updates
5
General Changes “Person with diabetes” vs. “diabetic” Support technology to assist diabetes management Obesity management/treatment recommendations Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 5
6
Testing All adults ≥45 years old regardless of weight Any person who is overweight/obese with ≥1 risk factor Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 6
7
Diabetes Management in Pregnancy A1c target 6-6.5% instead of 6% Insulin or metformin > glyburide Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 7
8
8
9
New Diabetes Therapies DPP-4 Inhibitors GLP-1 Agonists SGLT2 Inhibitors New Basal Insulins New Bolus Insulins
10
Where do diabetes meds work? Liver Intestines Brain Pancreas Muscle and Adipose ↓ glucose production ↑ insulin secretion ↑ satiety ↑ peripheral glucose uptake ↓ digestion and absorption of carbs Delay gastric emptying Kidneys ↓ glucose reabsorption SGLT2 inh Insulin Metformin TZDs Pramlintide DPP-4 inh. Incretin mimetics Insulin Sulfonylureas Meglitinides DPP-4 inh. Incretin mimetics Pramlintide Incretin mimetics Insulin Metformin TZDs Metformin a-glucosidase inh. Pramlintide Incretin mimetics 10
11
What level do they fix? FASTINGMIXEDPOSTPRANDIAL Interm. insulin Long insulin Regular insulin Rapid insulins Metformin SU Meglitinides TZDs a-glucosidase (-) DPP-4 (-) SGLT2 (-) Incretin mimetics (Exen.) Incretin mimetics Pramlintide 11
12
Incretin Effect Eat food nutrients and glucose in the gut Intestinal mucosal cells sense this and release hormones called incretins GLP1 = glucagon like peptide 1 GIP = glucose-dependent insulinotropic polypeptide The “incretin effect” is decreased in type 2 diabetes, so we need to replace levels. Idris I. Diabetes Obes Metab 2007;9:153-65. 12
13
Need for Drug Therapy That: Inhibits degradation of DPP-4 so there is more circulating incretin; DPP-4 inhibitors OR Replaces incretin altogether by giving an analog exogenously Incretin mimetic, or GLP-1 receptor agonist 13
14
Dipeptidyl Peptidase - 4 (DPP-4) Inhibitors Sitagliptin (Januvia)Saxagliptin (Onglyza) + Metformin (Janumet, XR) + Simvastatin (Juvisync) + Metformin (Kombiglyze XR) Linagliptin (Tradjenta)Alogliptin (Nesina) + Metformin (Jentadueto) + Empagliflozin (Glyxambi) + Metformin (Kazano) + Pioglitazone (Oseni) Lexi-complete Online. Accessed 4/7/16. 14
15
DPP-4 Inhibitors Mechanism: Inhibits DPP-4 (enzyme that breaks down incretin) Increased circulating incretin, helping control glucose absorbed in the diet Glucose-dependent increase in insulin secretion Glucose-dependent inhibition of glucagon secretion Idris I. Diabetes Obes Metab 2007;9:153-65. Drucker DJ. Lancet 2006;368:1696-705. 15
16
DPP-4 Inhibitors - Safety AE: Placebo-like: HA, URI, nasopharyngitis, UTI Rare: pancreatitis, skin reactions, urticaria/angioedema CI: Hx of pancreatitis, DKA, type 1 diabetes Counseling: With or without food Lexi-complete Online. Accessed 4/7/16. 16
17
DPP-4 Inhibitors - Efficacy Average A1c reduction: 0.6-0.8% Primarily acts on postprandial glucose Remember they are glucose-dependent 17
18
DPP-4 Inhibitors Advantages: No hypoglycemia as monotherapy Weight neutral Placebo-like AE Beta cell preservation Linagliptin – no renal adjustments needed Disadvantages: Modest A1c lowering Cost Long term safety unknown 18
19
DPP-4 Inhibitors Dosing Guide Sitagliptin 100mg po daily CrCl 30-49= 50mg po daily CrCl ≤ 30= 25mg po daily ESRD= 25mg po daily without regard to HD Reduce dose of concomitant insulin/secretagogues Saxagliptin 2.5 – 5mg po daily CrCl ≤ 50 = 2.5mg po daily ESRD = 2.5mg po daily, post-HD With strong CYP 3A4/5 inhibitors (“conazoles” and protease inhibitors) = 2.5mg po daily Reduce dose of concomitant insulin/secretagogues Lexi-complete Online. Accessed 4/7/16. 19
20
DPP-4 Inhibitors Dosing Guide Linagliptin 5mg po daily Reduce dose of concomitant insulin/secretagogues No renal dose adjustment needed Alogliptin 25mg po daily CrCl 30-59= 12.5mg po daily CrCl 15-29= 6.25mg po daily ESRD= 6.25mg po daily, without regard to HD Reduce dose of concomitant insulin/secretagogues Lexi-complete Online. Accessed 4/7/16. 20
21
GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Exenatide (Byetta, Bydureon) Liraglutide (Victoza, Saxenda) Albiglutide (Tanzeum) Dulaglutide (Trulicity) Lixisenatide (Lyxumia) App. for new drug approval submitted 9/2015 Lexi-complete Online. Accessed 4/7/16. FDA Drugs. Accessed 4/11/16. 21
22
Mechanism: GLP1 analog Increases incretin levels Glucose-dependent increase in insulin secretion Glucose-dependent inhibition of glucagon Reduces gastric emptying Increases satiety GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Lexi-complete Online. Accessed 4/7/16. 22
23
Adverse Effects: Nausea – 8-40% more vs. placebo/comparator Exen BID>Lira>Exen Q7D>Alb/Dula Diarrhea – 3-118% more vs. placebo/comparator Rare – pancreatitis, renal dysfunction, thyroid tumors CI: Gastroparesis Pancreatitis Exen: CrCl <30 (maybe others?) Lira, Alb, Dula, Exen: PMH or FH of thyroid cancer, multiple endocrine neoplasia GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Shyangdan DS. Cochrane Database Syst Rev 2011. Lexi-complete Online. Accessed 4/7/16. 23
24
GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Efficacy: A1c reduction 1-2% Adjunct for type 2 diabetes BID = More postprandial reduction Daily, Q7D Dosing = More fasting reduction Drucker DJ. Lancet 2006;368:1696-705. Lexi-complete Online. Accessed 4/7/16. 24
25
GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Dosing considerations Inject into thigh, abdomen, upper arm Exenatide BID 60 minutes prior to 2 main meals Reduce incidence of nausea with proper dose titration (start low, go slow) Once-weekly injections < twice daily injections Lexi-complete Online. Accessed 4/7/16. 25
26
Start weekly dose the day after D/C IR D/C IR Monday, start ER Tuesday Pt may have increased BG levels for 2 weeks Pretreatment for this temporary rise is unnecessary Exenatide IR to ER Lexi-complete Online. Accessed 4/7/16. 26
27
GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Advantages: Weight loss – 1-5kg No priming after initial dose Extended release option available Preservation of beta cell function Decrease insulin resistance Shyangdan DS. Cochrane Database Syst Rev 2011. 27
28
GLP 1 Receptor Agonists (a.k.a. incretin mimetics) Disadvantages: May reduce absorption rate and extent of drugs requiring rapid absorption (i.e. pain relievers, antibiotics, BCPs). Separate by 1 hour. Requires subcutaneous injection Cost GI side effects Lexi-complete Online. Accessed 4/7/16. 28
29
GLP-1 Agonists Dosing Guide Byetta (exenatide) 5mcg subq BID ac, increase to 10mcg subq BID after 1 month CrCl <30= use is not recommended Bydureon (exenatide) 2mg subq once weekly CrCl <30= use is not recommended Victoza (liraglutide) 0.6 mg subq once daily x 1 week, then increase to 1.2mg subq once daily. May go to 1.8mg if optimal glycemic response not achieved. If missed doses, resume with next scheduled dose. If >3 days of missed doses, resume with 0.6mg dose and retitrate. No CrCl limitations on use Lexi-complete Online. Accessed 4/7/16. 29
30
GLP-1 Agonists Dosing Guide Tanzeum (albiglutide) 30mg subq once weekly, may increase to 50mg once weekly if inadequate response at week 12. Missed dose = administer ASAP within 3 days. If >3 days have passed, omit dose and resume with next scheduled dose. No renal adjustment necessary. Trulicity (dulaglutide ) 0.75mg subq once weekly; may increase to 1.5mg weekly if inadequate response. Same missed dose regimen as albiglutide No renal adjustment necessary. Lyxumia (lixisenatide) – once daily prandial subq injection, dose TBA Lexi-complete Online. Accessed 4/7/16. 30
31
Incretin Mimetic vs. DPP-4 Inhibitors Incretin MimeticDPP-4 Inhibitor Delay gastric emptyingNo effect on gastric emptying Increase satietyNo increase in satiety Lots of N/VPlacebo-like AE Weight lossNo change in weight SC administrationPO administration Drucker DJ. Lancet 2006;368:1696-705. 31
32
SGLT2 Inhibitors Canagliflozin (Invokana)Dapagliflozin (Farxiga) Approved 3/13 + Metformin (Invokamet) Approved 1/14 + Metformin (Xigduo) Empagliflozin (Jardiance) Approved 8/14 + Metformin (Synjardy) + Linagliptin (Glyxambi) Lexi-complete Online. Accessed 4/7/16. 32
33
SGLT2 Inhibitors Mechanism of Action Blocks renal absorption of ~90% of excess glucose Causes renal wasting of glucose, lowering serum BG and A1c over time Minimizes chance of hypoglycemia Jurczak MJ. Diabetes 2011;60:890-8. Lexi-complete Online. Accessed 4/7/16. 33
34
SGLT2 Inhibitors Adverse Effects: Urinary/genital infections Hypotension Bone fractures DKA Hyperkalemia Renal insufficiency Contraindications: Hypersensitivity ESRD/Dialysis Lexi-complete Online. Accessed 4/7/16. 34
35
SGLT2 Inhibitors Counseling Points: With or without food Before the first meal of the day Efficacy 0.5-0.9% A1c lowering Mostly post-prandial glucose lowering Lexi-complete Online. Accessed 4/7/16. 35
36
SGLT2 Inhibitors Advantages: New mechanism, another option Less hypoglycemia Weight loss Potential BP- lowering Disadvantages: DKA Price / insurance coverage May encourage diet indiscretions? Cancer risk? 36
37
Dosing Recommendations Canagliflozin (Invokana) 100mg po once daily before first meal of the day eGFR 45-59 = 100mg po daily max eGFR <45 = use is not recommended/CI Dapagliflozin (Farxiga) 10 mg po once daily without regard to meals eGFR <60 = use is not recommended/CI Empagliflozin (Jardiance) 10mg po once daily without regard to meals eGFR <45 = use is not recommended/CI Lexi-complete Online. Accessed 4/7/16. 37
38
Type 2 Therapies (Fig 7.1) Cefalu WT. Diabetes Care 2016;29(1):S1-S112. 38
39
New Insulin Therapies
40
Ideal basal insulin Peakless Consistent rate of absorption No weight gain True 24-hour coverage Bolus insulin Lots of injections Titratable dose Minimize side effects 1. Insulin degludec (Tresiba) 2. Insulin glargine (Toujeo) 3. Insulin glargine (Basaglar) 4. Humalog U-200 KwikPen 5. Inhaled insulin (Afrezza) Hess R. ACSAP 2016;1:35-64. 40
41
Insulin degludec (Tresiba) Image: https://www.diabetesdaily.com/blog/2015/09/tresiba-fda-approves-new-basal-insulin-in-the-usa/. Accessed 4/11/16.https://www.diabetesdaily.com/blog/2015/09/tresiba-fda-approves-new-basal-insulin-in-the-usa/ 1 1 41
42
Insulin degludec (Tresiba) Long-acting insulin Onset = 1 hour Time to peak = 9 hours t ½ = 25 hours Duration = 42 hours Lexi-complete Online. Accessed 4/7/16. 42
43
Insulin degludec Mechanism Naturally, insulin dimers form hexameric complexes to maximize storage within beta-cell vesicles Degludec mimics this natural process Hexamer multihexameric chain = depot formation with a slow constant release over time Jonassen I. Pharm Res 2012;29:2104-14. 43
44
Head-to-Head: Insulin degludec vs. Insulin glargine Noninferiority criteria met (95% CI -0.14 to 0.11) Nocturnal hypoglycemia rates 25% lower (p=0.021) Mean weight gain similar (1.8 kg with degludec and 1.6 kg with glargine) (p=0.62) Insulin detemir (+ aspart) Noninferiority criteria met (95% CI -0.23 to 0.05) Nocturnal hypoglycemia 34% lower (p=0.0049) Weight gain higher with degludec (est. diff. 1.08 kg; p<0.0001) Heller S. Lancet 2012;379:1489-97. (BEGIN) Mathieu C. J Clin Endocrinol Metab 2013;98:1154-62. (BEGIN:Flex T1) 44
45
HbA1c Comparison Mathieu C. J Clin Endocrinol Metab 2013;98:1154-62. (BEGIN:Flex T1) 45
46
Insulin degludec (Tresiba) 100 units/mL and 200 units/mL available No conversion calculation necessary; same unit per unit dose Dosing: Type 1: 0.2-0.4 units/kg (1/3-1/2 the TDD) Type 2: 10 units once daily Missed doses: administer ASAP to ensure at least 8 hours between doses Stable at room temp for 8 weeks Mathieu C. J Clin Endocrinol Metab 2013;98:1154-62. (BEGIN:Flex T1) Lexi-complete Online. Accessed 4/7/16. 46
47
Insulin glargine (Toujeo) Image: https://www.toujeo.com. Accessed 4/7/16. 2 2 47
48
Insulin glargine (Toujeo) No change in physiological mechanism Smaller amount of depot insulin Smaller surface area More gradual and prolonged release of hexamers Smaller amount of liquid per unit 450 units (300 u/mL) vs. 300 units (100 u/mL) in Lantus pen Home PD. Am Diabetes Assoc 2014;2014:abstract 80-LB. 48
49
Head-to-Head: Toujeo vs. Lantus Noninferiority met at 26 weeks (95% CI 0.1- 0.19) Nocturnal hypoglycemia 31% lower in first 8 weeks (CI 0.53-0.91) No difference at 26 weeks Less weight gain (est. diff. 0.5 kg, p=0.037) Home PD. Am Diabetes Assoc 2014;2014:abstract 80-LB. 49
50
Basaglar (insulin glargine) Eli Lilly/Boerhinger Ingelheim. Introducing: Basaglar. https://www.basaglar.com/# (accessed 4/7/16).https://www.basaglar.com/# 3 3 50
51
Basaglar (insulin glargine) Lilly/BI’s answer to Sanofi-Aventis’s Lantus Same PK profile, not interchangeable Approved for use in type 1 kids and adults, and type 2 adults Available starting 12/2016 Blevins TC. Diabetes Obes Metab 2015;17:726-33. (ELEMENT 1) Eli Lilly/Boerhinger Ingelheim. Introducing: Basaglar. https://www.basaglar.com/# (accessed 4/7/16).https://www.basaglar.com/# 51
52
Head-to-Head: Basaglar vs. Lantus Noninferiority met at 24 weeks 95% CI -0.002 to 0.219 Symptomatic and nocturnal hypoglycemia similar Weight gain similar 0.36 kg Basaglar vs. 0.12 kg Lantus Insulin antibodies similar Blevins TC. Diabetes Obes Metab 2015;17:726-33. (ELEMENT 1) 52
53
Humalog U-200 KwikPen Image: http://www.ulticare.com/pen-needles/. Accessed 4/11/16. 4 4 53
54
Humalog U-200 KwikPen 200 units/ml 600 units/pen (versus 300 units/pen) Good for patients who go through 2 or more mealtime insulin pens each month Lexi-complete Online. Accessed 4/7/16. 54
55
Inhaled insulin (Afrezza) Images: Afrezza. https://www.afrezza.com/hcp 5 5 55
56
Inhaled insulin (Afrezza) “Technosphere insulin” Helps reduce injection barriers to therapy Lungs have a large surface area and high bioavailability New inhaler device called “Dreamboat” Replace every 15 days Insulin cartridges available: 4 units, 8 units, 12 units Concerns: pulmonary toxicity/malignancy Lexi-complete Online. Accessed 4/7/16. Bode BW. Diabetes Care 2015;38:2266-73. Raskin P. Diabetes Obes Metab 2012;14:163-73. 56
57
Head-to-Head: Inhaled insulin vs. aspart Mean change in HbA1c noninferior More aspart patients achieved HbA1c <7.0% (30.7% vs. 18.3%) Inhaled insulin had less hypoglycemia (9.8 vs 14.0 events/patient-month, p<0.0001) Inhaled insulin patients experienced weight loss (-0.4 kg) vs. gain (+0.9 kg) for aspart patients (p=0.0102) Most frequent AE = cough which led to discontinuation in 5.7% of patients Bode BW. Diabetes Care 2015;38:2266-73. 57
58
Dosing Chart Configurations Afrezza. https://www.afrezza.com/AfrezzaConfigurationChart.pdf 58
59
Diabetes Meds in the Pipeline Novo Nordisk Xultophy (insulin degludec + liraglutide) Faster-acting insulin aspart Semaglutide (oral and injectable) Eli Lilly BioChaperone insulin lispro R&D Pipeline. http://www.novonordisk.com/rnd/rd-pipeline.html. Accessed 4/11/16. Anderson G. Diabetes 2014;63(suppl 1). 59
60
60
61
Innovative Care Solutions and Ideas Patient Assistance Programs Coupons Medication Pricing Apps Medication Lists
62
Patient Assistance Programs (PAPs) Provided by pharmaceutical companies To provide brand-name medications For low-income individuals who lack prescription drug coverage Vs. coupon, sample, 340B, drug card, bulk replacement programs, and Medicare Part D Advocate “PAPs are a long term solution to a current medication access problem” Am J Health-Syst Pharm. 2006; 63:1254-9. Sagall RJ. Pharmaceutical companies helping patients get their medications. Accessed at http://www.needymeds.org/indices/article.htm on 2/21/13. 62
63
Programs Available NeedyMeds http://www.needymeds.org http://www.needymeds.org Partnership for Prescription Assistance http://www.pparx.org http://www.pparx.org RxAssist http://www.rxassist.org http://www.rxassist.org TogetherRx Access http://www.togetherrxaccess.com http://www.togetherrxaccess.com National Council on Patient Information and Education http://www.talkaboutrx.org http://www.talkaboutrx.org Manufacturers’ websites 63
64
Finding an application Medications covered Type (brand, generic) Insurance status Private insurance Medicare Part D (coverage gap) No insurance 64
65
Coupons Discount the price of medications for a set number of fills Search patient assistance websites for coupons Hard copy cards at physician offices from drug company representatives 65
66
Medication Pricing - GoodRx Losartan 50mg #30 Wal-Mart pricing by phone = $39.41 Price obtained by phone from Wal-Mart Neighborhood Market, 4404 S. Peoria Ave. Tulsa, OK on 4/11/16. 66
67
Medication Pricing - GoodRx Screenshots taken 4/7/16. 67
68
Medication Pricing - GoodRx Screenshots taken 4/7/16. 68
69
Medication Lists MyMedSchedule.com 69
70
Medication Lists My Medicine List http://www.safemedication.com 70
71
Questions?
72
Diabetes Update 2016: New Drugs and New Methods of Care Kelly Murray, PharmD, BCACP Clinical Assistant Professor of Clinical Pharmacy OSU College of Osteopathic Medicine Emergency Department Clinical Pharmacist OSU Medical Center
Similar presentations
© 2025 SlidePlayer.com Inc.
All rights reserved.