Up to Date for Diabetes: Veronica Piziak MD, PhD Professor of Medicine Texas A&M Emeritus Director of Endocrinology Baylor Scott and White

Transcription

1 Up to Date for Diabetes: Veronica Piziak MD, PhD Professor of Medicine Texas A&M Emeritus Director of Endocrinology Baylor Scott and White

2 Objectives: What is New in Therapy How to select medications

3 Disclosures: Janssen Pharmaceutical research support, Local Principal Investigator No investigational use mentioned

4 Individualize Therapy Type 1 Diabetes Type 2 Diabetes 250 # 84 # Permission Williams Endocrinology

5 HgA1c Primary Method for Screening Venous sample, nonfasting More convenient, less variable then blood glucose Allowed screening for prediabetes OK to use at first prenatal visit (2014) 2 hr OGGT will diagnose more people with diabetes A1c not useful in states of abnormal red cell turnover: cystic fibrosis, recent blood loss, transfusion, hemolytic anemia.

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7 A1c primary screening method Prediabetes % 12% of the population Diabetes 6.5% 9.9% of the population Mean A1c in nonobese patients without diabetes is 5.0% Mean A1c in the US is 5.36% AACE prediabetes = 5.5% NHANES 2010 data

8 Age-standardized prevalence estimates for poor, intermediate, and ideal cardiovascular health for each of the 7 metrics of cardiovascular health in the American Heart Association 2020 goals among US adults aged 20 years, National Health and Nutrition Examination Go A S et al. Circulation. 2014;129:e28-e292.

9 CASE 1 At risk for diabetes? When would you screen? 35 yo lady 5 tall, 120 pounds BP 150/90 Difficulty becoming pregnant Irregular menses, excess facial hair Family history of diabetes Low HDL, high triglycerides A1c was 6.8%

10 American Diabetes Association. Diabetes Care Hyperglycemia ADA Treatment Goals FPG/ mg/dl Hypertension Dyslipidemia PPG A1C Blood pressure Take one at bedtime LDL HDL Triglycerides <180 mg/dl < 7%? lowest possible without hypoglycemia < 140/<80 Use ACE I or ARB < 115/75 higher mortality <100 mg/dl, patients with diabetes (30-40% reduction) <70 mg/dl, very high risk patients with diabetes and CVD >50 mg/dl, women >40 men < 150mg/dl

11 ADA guidelines 2014 Individualize treatment goals A1c Hypoglcemic unawareness

12 Case 2 73 yo lady is referred from the emergency department after a head injury when she had a seizure from hypoglycemia, lives alone She takes metformin 500mg HS and glyburide 5mg BID since diagnosed in She has glucose values in the 50 s 3-4 times a week in the afternoon. A1c is 7.2%. She wants it to be <7% She no complications from diabetes FDA warning about glyburide

13 Lipid Control ADA/AACE Measure lipids annually Total cholesterol HDL Triglycerides Calculate LDL Triglycerides >400 Use Non HDL as treatment goal

14 Lipid Control ADA/AACE Statin therapy + lifestyle therapy, regardless of baseline lipid levels with overt CVD without CVD >/= age 40 one or more other risk factors family history of early CVD, hypertension, smoking, dyslipidemia, albuminuria, obesity

15 Lipid Therapy ADA/AACE Low-risk patients No CVD and under age 40 lifestyle Statin therapy should be considered If LDL >/= 100 mg/dl or multiple risk factors Type 1 diabetes of 10 or more years duration with LDL >/= 100 Remember effective contraception

16 ADA/AACE Lipid Goals LDL goal -- no known CVD < 100 LDL goal -- known CVD < 70 is an option Combination therapy not recommended Triglycerides 1000 mg% or less lifestyle modification > 1000 mg% Fibric acid derivatives, Niacin, Fish oil

17 When to use Aspirin Use aspirin therapy ( mg/day) Diabetes with a history of CV Primary prevention for those with risk factors family history of early CVD, hypertension, smoking, dyslipidemia, albuminuria, obesity Aspirin for adults with diabetes at low risk men aged 50 +, women aged 60 +

18 ADA RENAL GUIDELINES Annual Urine Albumin Screening Treat albuminuria > 300 mg/day with ACE or ARB May treat albuminuria > 30 mg / day with ACE or ARB Annual serum creatinine Estimate GFR Stage 4 or more refer Diabetes Care calculator.cfm

19 ADA Dietary Recommendations All patients with diabetes should have dietary instruction Carbohydrate counting should be taught to patients with Type 1 diabetes, may be taught in Type 2 There was no ideal macronutrient distribution and macronutrient proportions should be individualized.

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21 Bariatric Surgery Bariatric surgery may be considered: Type 2 diabetes - BMI 35 kg/m2 + difficult to control with lifestyle and pharmacological therapy Particularly if there are comorbidities dyslipidemias

22 Gastric bypass 8 years, 83% of patients with preoperative T2DM had normal levels of plasma glucose, Hypertension - not different Sleep apnea not resolved in most Dyslipidemia improved in majority.canadian Journal of Surgery 2013 Feb;56(1):47-57.

23 Bariatric surgery is now recommended by the ADA for type 2 diabetes Gastric Sleeve Gastric bypass

24 Treating Type 2 Diabetes: Medications to address: Insulin resistance Beta and Alpha Cell Dysfunction

25 Classical Antidiabetic agents Intestine: glucose/fat absorption decreased digestion of carbohydrate/fat Acarbose/ Xenical, bile acid binding resin Rosiglitazone is back! Muscle and adipose tissue: glucose uptake/ glucose utilization Metformin, TZDs 1 Liver: hepatic glucose output Metformin HGO Insulin resistance Blood glucose TZD s preserve Beta cell function Decreases cancer risk and prolongs survival in cancer patients Insulin resistance Pancreas: insulin secretion Sulfonylureas, nateglinide DeFronzo RA. Diabetes. 1988;37: Lebovitz HE. In Joslin's Diabetes Mellitus. 1994: ; Amatruda JM. In: Diabetes Mellitus DeFronzo RA et al. J Clin Endocrinol Metab. 1991;73: Whitcomb RW et al. In: Diabetes Mellitus. 1996;Cavaghan MK et al. J Clin Invest. 1997;100: Ehrmann DA et al. J Clin Endocrinol Metab. 1997;82: ; Wolffenbuttel BHR. Eur J Clin Pharmacol. 1993;45:

26 GLP 1 Receptor Agonists Exenatide Byetta Extended Release Exenatide -Bydureon Liraglutide Victoza Albiglutide - Tanzeum Injectables Reduce post meal glucose % May result in significant weight loss Should not be used in gastroparesis or stage 4 renal insufficiency

27 DPP-4 Inhibitors Oral agents Sitagliptin Saxagliptin Lower postmeal glucose Linaglipitin Lower A1c about 0.5-1% May be used with dose adjustment in renal insufficiency Weight neutral

28 DPP-4 Inhibitors GLP-1 Receptor Agonists FDA is reviewing data linking these medication classes to pancreatitis and pancreatic and thyroid neuroendocrine tumors BMJ 2013;346:f3750 Discuss symptoms of pancreatitis - tell patient to discontinue if they occur. Ask about risk factors pancreatitis FDA is reviewing the data associating Saxagliptin with CHF NEJM 2013:369,

29 Bile Acid Binding Resin Colesevelam (Welchol) Approved for use in Type 2 diabetes Lowers A1c by 0.8% 625 mg x 6/day Add on to metformin May increase triglycerides when used with sulfonylurea or insulin. Don t use when triglycerides are >500 Many have GI side effects May cause malabsorption of medications Useful- add on to control LDL

30 Cycloset - bromocriptine Quick-release formulation of bromocriptine that increases CNS dopaminergic activity. Lowers the A1c by about 0.8 % Weigh neutral, no hypoglycemia Nausea is the major side effect Initial dose is one 0.8 mg tablet daily, titrated weekly by 1 tablet until therapeutic dose (1.6 to 4.8 mg, or between 2 and 6 tablets per day) is achieved.

31 Improvement in Cardiovascular Risk Factors with 3.5 Years of Exenatide GLP=1 Anagonist LDL-C (mg/dl) ± Treatment (n = 151) Change from Baseline Systolic Blood Pressure (mmhg) -3.5 ± 1.2-2% Diastolic Blood Pressure (mmhg) -3.3 ± 0.8-4% HDL-C (mg/dl) 8.5 ± % Triglycerides (mg/dl) ± % Total Cholesterol (mg/dl) ± 3.1-5% Weight loss avg 5.3 kg Klonoff DC, et al. Curr Med Res Opin 2008;24: Nausea main side effect (use 20 minutes before meals), pancreatitis possible. Do not use Cr Cl <30 Caution CrCl <50 Now approved for add on to basal insulin

32 Exenatide Extended Release - Bydureon Administered 2 mg subq once/week Takes about 2 weeks to reach steady state Not recommended for first line therapy Add on to metformin, SU, TZD Reduced A1c by 1.6% (exenatide 0.9%) Reduced A1c by 1.5% vs sitagliptin 0.9% Weight loss 5# 24 weeks A1c changes sustained at 1 year Store in fridge!

33 Exenatide Extended Release - Bydureon Side effects: Nausea 14% vs 35% exenatide Diarrhea 9.3% vs 4.1% Injection site reactions 5.4% vs 2.4 % Hypoglycemia may occur when combined with sulfonylureas Do not use in gastroparesis or Cr Cl <30 Precautions: Causes an increase in C cell tumors in rats unknown risk in humans Do not use in patients with a family hx or personal hx of medullary carcinoma of the thyroid. Associated with angioedema Has been associated with pancreatitis

34 0.6 mg / day starting dose Liraglutide (Victoza) Titrate mg / day Multidose pens Reduces postmeal glucose (A1c 1% lower) Nausea most common side effect Use with metformin, sulfonylureas, TZD Weight loss 2 kg/26 weeks Associated with pancreatitis in rare instances Medullary carcinoma in animals Don t use in patients with a family history of medullary carcinoma

35 Sitagliptin: Once-Daily Dosing Proven 24- Hour Glycemic Control Patients With Renal Insufficiency*, A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with end-stage renal disease requiring hemodialysis or peritoneal dialysis. 50 mg once daily 25 mg once daily Moderate CrCl 30 to <50 ml/min (~Serum Cr levels [mg/dl] Men: > ; Women: > ) Severe and ESRD CrCl <30 ml/min (~Serum Cr levels [mg/dl] Men: >3.0; Women: >2.5) Assessment of renal function is recommended prior to initiation and periodically thereafter. * can be taken with or without food. Patients with mild renal insufficiency 100 mg once daily. ESRD=end-stage renal disease requiring hemodialysis or peritoneal dialysis.

36 Saxagliptin (Onglyza) 2.5, 5 mg Lowers A1c about 0.5-1% May be used with dose adjustment in renal insufficiency No weight loss Increased risk for CHF?

37 Linaglipitin (Tradjenta) Approved for type 2 diabetes DPP-4 inhibitor Monotherapy, combination with Metformin,Sulfonylurea, pioglitazone A1c decreased 0.7% Only 1 dose 5mg/day

38 SGLT2 Inhibitors A new class of drug for diabetes

39 Renal tubular regulation of glucose reabsorption. Abdul-Ghani M A et al. Endocrine Reviews 2011;32:

40 Glucose reabsorption and excretion by the kidney. Abdul-Ghani M A et al. Endocrine Reviews 2011;32:

41 Effects of SGLT 2 Inhibition Increased glucose loss Decreased A1c Increased calorie loss Weight loss Increased sodium loss? Decreased BP Rare hypoglycemia

42 Adverse effects High urine glucose Increased urinary tract infection 5% Increased mycotic infections 7-10% Osmotic diuresis Dehydration Hypotension Decreased renal function Hyperkalemia Drink plenty of water!

43 Canagliflozin (Invokana) Doses 100mg, 300 mg A1c decreased by 1.16% Weight decreased by 3.3% Hypoglycemia 3.0% Mild Not to be used egfr <45

44 Dapagliflozin (Farxiga) 5 mg, 10 mg A1c decreased by 1.5 % Weight decreased by 1.5% (lose 280 cal/day) Hypoglycemia rare e GFR < 60 don t use Do not use in patients with bladder cancer

45 Action Profiles of Insulins IP Aspart, glulisine, lispro 4 5 hours Plasma Insulin Levels Regular 6 8 hours NPH hours Detemir ~14 24 hours Glargine ~24 hours Hours Burge MR, Schade DS. Endocrinol Metab Clin North Am. 1997;26: ; Barlocco D. Curr Opin Invest Drugs. 2003;4: ; Danne T et al. Diabetes Care. 2003;26:

46 Inhaled Powdered Insulin Afrezza Ultra rapid acting insulin instant absorption Peaks within minutes Proven reductions in HbA1c A reduced risk of hypoglycemia vs. rapidacting analogs Less weight gain vs. rapid-acting analogs Injection-free insulin delivery

47 Inhaled Powdered Insulin Afrezza Must have pulmonary function test ( FEV1) before using Cannot use in patients with asthma or COPD May result in acute bronchospasm FDA mandated further studies to look for long term effects on the lungs

48 Inhaled Powdered Insulin Afrezza

49 SMBG Guidelines The frequency and timing of SMBG should be dictated by the particular needs and goals of the patient Pump therapy 6-8 times per day Type 1 basal bolus 5 x / day maximum Type 2 on insulin 3 x per day Type 2 oral agents may be helpful? Need to be instructed about how to use to adjust therapy. You must document number of glucose checks in chart 1/ day- oral agents, 3/day insulin Keep those downloads!

50 Medication Type 2 Diabetes(ADA) Initially metformin is preferred If target A1c not achieved over 3-6 months: Add second oral agent or insulin Patient centered approach for further oral agents Evidence suggests that there is no single best choice for everyone beyond metformin Insulin therapy is eventually indicated for many patients with Type 2 diabetes

51 AACE Goals Control glucose Avoid hypoglycemia Avoid weight gain Patient satisfaction

52 Case 2 73 yo lady was referred from the emergency department after a head injury when she had a seizure from hypoglycemia She still takes metformin 500mg HS She has glucose values in the 200 s 3-4 times a week in the afternoon. e GFR is 48 A1c is 8.0%. She wants it to be <7% What is the goal? ADA says 7.5%+ Where is the problem? Post meal

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54 Case 3 56 yo lady with diabetes for 9 years A1c 9.2 % BP 150/80 p88, BMI 34 S/p MI and stroke, egfr 56 What is our A1c goal? Taking maximum metformin, glyburide blood sugars AM 140mg% HS 280mg% Where is the problem? What to do? Can we use basal insulin? What will change the A1c by 1.5%? Post meal

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57 Case 4 45 yo male with Type 2 diabetes for 3 years Normal exam, uncircumcised, BMI 34 No know complications A1c 7.9% A1c goal? Taking metformin 1000 mg BID Avoid hypoglycemia, Avoid weight gain Post meal problem Decrease carbohydrate, increase exercise

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60 Summary: Try A1c for diagnosis Treat type 2 diabetes early aggressive therapy Longer duration, more comorbidities A1c goal is higher, avoid hypoglycemia 7.5% Check blood sugars as needed to adjust therapy Customize therapy for each patient.