Diabetes 2016: Strategies for achieving optimal diabetes control

PHASE Safety Net Community Benefit Diabetes 2016: Strategies for achieving optimal diabetes control Presented by: Lisa Gilliam, MD, PhD Clinical Leader Diabetes Program Kaiser Permanente Northern California October 26, 2016

Dr. Lisa Gilliam Clinical Leader, Kaiser Permanente Northern California Diabetes Program

What is optimal diabetes control? 10 years ago A1c < 7% for most The lower, the better One size fits all ACCORD ADVANCE VADT Standards of Medical Care in Diabetes 2012 The ADA proposes optimal targets, but each target must be individualized to the needs of each patient and his or her disease factors

What is optimal diabetes control in 2016? Most people - A1c goal <7% Lower targets (ex: <6.5%) Short duration of DM T2D treated with lifestyle or metformin only Long life expectance No significant CVD Only if this can be achieved without significant hypoglycemia or other adverse effects of treatment Higher targets (ex: <8%) Severe hypoglycemia Limited life expectancy Advanced microvascular or macrovascular complications Extensive comorbid conditions Long-standing DM in whom general goal is difficult to attain

How does a health plan achieve optimal A1c control? Piling on?

Kaiser Permanente Northern California: Leader in diabetes control #9 in the US for A1c <8% 70% of DM patients have A1c under 8% Regional target = 73% 82% of DM patients have A1c under 9% Regional target = 86%

What has the KP NCal strategy been?? Alogliptin (Nesina) Lispro (Humalog) NPH insulin Empagliflozin (Jardiance) Regular insulin Linagliptin (Tradjenta) Metformin Pioglitazone (Actos) Glimiperide (Amaryl) Canagloflozin (Invokana) Saxagliptin (Onglyza) Dapagliflozin (Farxiga) Liraglutide inj (Victoza) Dulaglutide inj (Trulicity) Sitagliptin (Januvia) Glargine (Lantus) Glipizide (Glucotrol) Acarbose (Precose) Albiglutide inj (Tanzeum) Exenatide inj (Byetta) Exenatide ER inj (Bydureon)

Key Factors in NCAL Performance Technology Tools: PROMPT Responsibility: Accountable Population Managers, or APMs PharmDs or RNXs manage panels of patients with diabetes and other CV risk factors Accountability: PROMPT Reporting

OK, so what medications should I use??

Sulfonylureas Glipizide (Glucotrol), Glimiperide (Amaryl) - $ ($100/yr) Stimulates pancreatic beta cell insulin release Advantages Oral Affordable Long clinical exp. microvascular risk (UKPDS) Disadvantages Hypoglycemia risk 1-3% risk for severe hypoglycemia Weight gain (avg <5 kg) 1-2% A1c** **expected decrease in A1c (%) with MONOtherapy, actual A1c lowering when used as 2 nd or 3 rd line agent will be less

Thiazolidinediones (TZD) Pioglitazone (Actos) - $$ ($160/yr), Rosiglitazone (Avandia) - $$$$ ($3300/yr) Activates PPAR gamma, insulin sensitivity Advantages Oral Affordable No hypoglycemia Disadvantages Edema (25%) CHF <0.2% overall, 2-5% in high risk Contraindicated in III/IV CHF Weight gain (<5 kg) Fracture risk Bladder CA?-mixed data 0.5-1.4% A1c

SGLT2 inhibitors Empagliflozin (Jardiance), Dapagliflozin (Farxiga), Canagloflozin (Invokana) - $$$$ ($4700-4800/yr) Blocks renal glucose reabsorption, promotes glucosuria Advantages Oral Modest weight loss blood pressure Disadvantages Not affordable GU infections (10%) UTI/urosepsis, pyelonephritis DKA Polyuria/hypotension/dizziness Fracture risk Contraindicated for GFR<30 0.5-0.7% A1c

DPP-4 Inhibitors Linagliptin (Tradjenta), Sitagliptin (Januvia), Alogliptin* (Nesina), Saxagliptin (Onglyza) $$$ ($1460/yr) - $$$$ ($4400/year) Inhibits DPP-4 which GLP-1 GLP-1: food intake, gastric emptying insulin release, post-prandial glucagon Advantages Oral Weight neutral Generally few SEs Disadvantages Not affordable Angioedema/urticaria? Acute pancreatitis? CHF hospitalizations 0.5-0.8% A1c

GLP-1 receptor agonists Exenatide ER inj (Bydureon), Albiglutide inj (Tanzeum); Exenatide inj (Byetta), Liraglutide inj (Victoza), Dulaglutide inj (Trulicity) $$$$$ ($5000-$9000/yr) GLP-1: food intake, gastric emptying insulin release, post-prandial glucagon Advantages Modest weight loss Once weekly dosing Reduction in death from CVD Disadvantages Injected GI SE s (N/V, diarrhea in 20-40%)? Acute pancreatitis VERY expensive Contraindicated if FHx of MTC or MEN2 (Exenatide ER) 0.5-1% A1c

Basal Insulin NPH (Humulin N) - $$ -(~$500/year) Analogs - Glargine (Lantus), Detemir (Levemir), Degludec (Tresiba) - $$$$ - $$$$$ ($3000-$9000/year) Advantages Affordable (NPH vials) Unlimited efficacy Long clinical experience microvascular risk (UKPDS) Disadvantages Injected Hypoglycemia risk Weight gain (<5 kg)

How do we choose??

ADA Standards of Medical Care in Diabetes 2016 Diabetes Care 39:1 (2016) p S54.

Kaiser National Adult Diabetes Guidelines 2016

Case 1- what is the best choice for 3 rd line agent? Tobacco Red is a 48 year-old dye-worker with type 2 diabetes: Smokes 3 packs per day for the last 40 years He has beaten bladder cancer twice in last 10 years His current BMI is 55.3 Last three quarterly A1C levels were: 7.5% 7.8% 8.1% Current meds: Metformin XR 2 gm PO once daily Glipizide 10 mg PO bid Tobacco Red has been stable on this regimen for the last 3 years. At this point, the best course of action would be to...

Case 1- what is the best choice for 3 rd line agent? (A) Nothing - 8.1% is not bad, and this guy is likely to die from bladder cancer anyway. (B) Add Pioglitazone (Actos), retest in 3 months (C) Replace glipizide with bedtime NPH and titrate to a fasting glucose level <130. Retest in 3 months. (D) Replace glipizide with a Liraglutide (Victoza), retest in 3 months. (E) C or D Hints: Current meds = Metformin 2000 mg qd, Glipizide 10 bid Considerations: Obesity (BMI 55), smoker

Case 1- what is the best choice for 3 rd line agent? Answers: (A) No - technically correct but politically incorrect. (B) No - adding Actos will get you sued when he develops bladder cancer for the 3rd time (C) YES - is correct and cost effective (D) YES - is correct and Liraglutide (Victoza) have a weight negative effect, which this gentleman needs. It s possible this might reduce his risk for CVD death. However, this option is less costeffective. (E) YES either C or D is correct

Does Pioglitazone cause bladder cancer? Dormandy, Lancet 2005: 366, 1279 - PROspective pioglitazone Clinical Trial In macrovascular Events (PROactive) study YES Erdmann, Diabetes Obes Metab 2014: 16, 63 PROactive update NO Lewis, JAMA 2015: 314, 265 Cohort and nested case-control study NO Tuccori, BMJ 2016; 352:i1541 Cohort study YES AHRQ review (Diabetes Medications for Adults With Type 2 Diabetes: An Update, April 2016) - NO Used most rigorous evidence which evaluated people prospectively

Leader Trial - 2016 Liraglutide (Victoza) reduced death from CVD causes Hazard ratio, 0.87; 95% CI, 0.78 to 0.97 2.3 kg more weight loss ~80% had established CVD Unknowns: Helpful for primary prevention? Class effect? (Evaluation of Lixisenatide in Acute Coronary Syndrome (ELIXA) trial no CVD benefit)

Case 2 - what is Terry s next best course of action? Terry Treetrunklegs is a 55 year-old lover of salt with type 2 diabetes who recently graduated to the 4th stage of CHF. She is quite proud of her accomplishment and feels a debt of gratitude to her hubby Jim, who makes her six nightly margaritas with salt at her favorite Mexican Restaurant. Her weight has increased by 5 lbs over the last 12 hours. Terry has battled pancreatitis and won four different times. Terry currently takes glipizide 10 mg PO bid Her last three quarterly A1C values: 7.2% 7.8% 8.5%.

Case 2 - what is Terry s next best course of action? (A) Add metformin. Gradually titrate to 2,000 mg per day to avoid GI side effects. Retest in 3 months. (B) Add Pioglitazone (Actos) 15 mg. Titrate dose up over the next 6 months based on quarterly A1C values. (C) Increase glipizide to 20 mg PO BID and retest A1C in 3 months. (D) Stop glipizide and start bedtime NPH. Titrate to fasting glucose <130. Recheck an A1C 3 months after achieving a fasting glucose <130. (E) Add Exenatide (Byetta) to glipizide, retest in 3 months. Hints: Current meds = Glipizide 10 bid Considerations: Stage IV CHF, h/o recurrent pancreatitis

Case 2 - what is Terry s next best course of action? Answers: (A) NO - Metformin is contraindicated due to risk of lactic acidosis in acute CHF. (B) No Pioglitazone (Actos) contraindicated in CHF class 3 or higher. (C) NO - This will be inadequate to reduce her A1C by the 1.5% needed to achieve goal. (D) YES - Insulin is needed for this patient. Glipizide will be of little value once insulin is added, and it is an extra medication increasing the risk of polypharmacy effects. (E) NO - This is a good way to get sued when Jim and his margaritas provoke pancreatitis bout #5.

Case 3 Bernie s next steps? Bernie U. Rheinhard is a 57 year-old with type 2 diabetes whose last three hemoglobin A1C values were, in order, 7.9%, 8.5% and 8.9%. Meds: Metformin 2,000 mg once daily Glipizide 10 mg twice daily She has a prescription for fluconazole 150 mg orally one time for yeast infections with 11 refills, because you are tired of her once monthly e-mail complaining of a new yeast infection. Bernie is currently in your office because it "burns hard when she urines." Today is the fourth time she has been in your office with this complaint this year. While analyzing her urine results (nitrite positive), you recognize her A1C trend and decide to adjust her medication.

Case 3 Bernie s next steps? You decide to (A) Increase her glipizide to 20 mg orally twice daily (B) Add canagliflozin (Invokana) (C) Add pioglitazone (Actos) (D) Add bedtime NPH insulin (E) B or C

Case 3 Bernie s next steps? Answers: (A) NO - technically, she needs a 2.0% reduction in her A1C to achieve goal. No oral hypoglycemic will get her there, and increasing the dosage of one she is already taking most certainly will not get her to goal. (B) NO - this woman is a yeast producing factory who has had four UTIs in the last year. Canagliflozin will only cause more problems and cost a lot, without getting her to goal. (C) NO - This is wrong for the same reason that (A) is wrong. (D) YES - Insulin is the only medication likely to help her achieve the necessary A1C reduction. Cessation of glipizide is probably reasonable at this point. (E) NO - neither (B) or (C) is correct.

Case 4 Sugar s second choice? Sugar T. Lowe is a 77 yo lady with longstanding type 2 diabetes (>20 years) who has the local EMS team on her Christmas card list after several visits to the ED for hypoglycemia when she was previously taking glipizide. She also got to see her EMS friends recently after getting out of bed too quickly and conking her head on the nightstand, leading to unconsciousness. Recent A1c 8.4%. Meds: Metformin 1000 bid Donepezil (Aricept) for senior moments (she s very forgetful these days)

Case 4 Sugar s second choice? (A) Add Canagloflozin (Invokana). (B) Add Pioglitazone (Actos). (C) Start bedtime NPH. Titrate to fasting glucose less than 130. (D) Add Sitagliptin (Januvia). (E) B or D Hints: Current meds = Metformin 1000 mg bid Considerations: Hypoglycemia, longstanding DM, occasional dizziness, early dementia

Case 4 Sugar s second choice? Answers: (A) NO - Canagloflozin (Invokana) would not be a good option in an elderly patient with dizziness/fall risk because it lowers BP. (B) YES - Pioglitazone (Actos) would be a good option in this case, and is costeffective. Target A1c in this lady would be <8% because of history of severe hypoglycemia and comorbid conditions (early dementia), and this target would probably be readily achieved by adding pioglitazone, while you would not increase her risk for hypoglycemia. (C) NO with history of severe hypoglycemia on glipizide, NPH would not be a great option for this lady. (D) YES Sitagliptin (Januvia) would be a good option for the same reasons listed above for Pioglitazone (Actos). However, this option is less cost-effective. (E) YES - either (B) or (D) is correct.

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