Diabetes update - Diagnosis and Treatment

Transcription

1 Diabetes update - Diagnosis and Treatment Eugene J Barrett, MD,PhD Madge Jones Professor of Medicine Director, University of Virginia Diabetes Center Disclosures - None

2 Case 1 - Screening for Diabetes 45-year-old Caucasian male seen for his medical visit Mother (deceased) had type II diabetes His BMI is 29 kg/m2 He has mild hypertension (on HCTZ) No diabetes related symptoms

3 Question 1-should you screen for diabetes and how 1. Measure hemoglobin A-1 C 2. measure fasting glucose 3. perform a two hour glucose tolerance test 4. no testing required this year

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5 Case 2-lifestyle and metformin are not enough 60-year-old female with DM 2 (5 yrs), hemoglobin A-1 C 10.4% on metformin 1 g a.m./p.m., obese (BMI 34), dyslipidemia (triglyceride 833, HDL-C 25, LDL-C 115), status-post cholecystectomy. No known cardiac disease. Efforts at weight loss have been unsuccessful. No regular exercise.

6 Case 2- your treatment goals include everything except? A1C < 6% Triglyceride below 150 mg/dl Blood pressure below 135/85 Lifestyle change Addition of statin

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8 Case 2- Patient prefers not to take injections. Which of these options would lower A1c the most and act most quickly Add a gliptin Add a sulphonylurea Add a TZD Add a bile acid binding resin Add SGLT-2 inhibitor Add alpha-glucosidase inhibitor

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10 Anticipated A1c Decrease Therapeutic Efficacy > 1.5% 0.8%-1.5% 0.5%-0.8% Insulin GLP-1 RAs, metformin, SUs, TZDs, glinides, pramlintide SGLT2 inhibitor DPP-4 inhibitors, α-gis, bromocriptine, colesevelam

11 Anti-hyperglycemic Therapy Metformin Insulin Insulin analogs Sulfonylureas TZDs Meglitinides α-glucosidase inhibitors Lifestyle Bile acid sequestrants Amylin mimetics GLP-1 receptor agonists DPP-4 inhibitors Dopamine-2 agonists SGLT2 inhibitors

12 Normal Renal Glucose Physiology 90% of glucose is reabsorbed by SGLT2 SGLT2 Glucose Glucose filtration (180 g/day) 10% of glucose is reabsorbed by SGLT1 Minimal to no glucose excretion 1. Mather, A & Pollock, C. Kidney International. 2011;79:S1-S6 2. Wright EM. Am J Physiol Renal Physiol 2001;280:F Lee YJ, et al. Kidney Int Suppl 2007;106:S Hummel CS, et al. Am J Physiol Cell Physiol 2011;300:C14 21.

13 Dapagliflozin: Changes in HbA 1c at Week 24 Monotherapy Add-on to metformin Add-on to a SU Add-on to insulin * 0.84* 0.82* 0.96* p< p< p< p<0.001 Dapagliflozin (10 mg) Placebo Baseline HbA 1c : 7-9% 1. Ferrannini E et al. Diabetes Care 2010;33: Bailey CJ et al. Lancet 2010;375: Strojek K et al. Diabetes Obes Metab 2011;13: Wilding JPH et al. Ann Intern Med 2012;156:

14 IR Insulin, mu/l IR Insulin, mu/l The Incretin Effect in Subjects ± T2DM Control (n=8) T2DM (n=14) nmol / L nmol/l Time, min Time, min 180 Oral glucose load Intravenous (IV) glucose infusion Nauck M et al. Diabetologia. 1986;29:46 52.

15 Sitagliptin + Metformin or Pioglitazone Mean Change in A1c (24-weeks) Add-on to metformin Add-on to pioglitazone Mean Baseline A1c: ~ 8.0% 0 Placebo Sitagliptin 0 Placebo Sitagliptin % % % P< % P<0.001 Charbonnel et al. Diabetes Care. 2006;29: ; Rosenstock et al. Clin Ther. 2006;28:

16 Anti-hyperglycemic Therapy: Cost for 90 d supply Lifestyle free? Metformin $10 Insulin R or N $400 Insulin analogs $1200 Sulfonylureas $10 TZDs $48 Meglitinides $70 α-glucosidase $130 inhibitors Bile acid sequestrants $690 Amylin mimetics $700 GLP-1 receptor agonists $1800 DPP-4 inhibitors $980 Dopamine-2 agonists $240 SGLT2 inhibitors $930

17 New Classes in Development Long-acting GLP-1R agonists Ranolazine Dual & pan PPAR agonists 11 Hydroxysteroid dehydrogenase-1 inhibitors Fructose 1,6-bisphosphatase inhibitors Glucokinase activators G protein-coupled receptor-40 & -119 agonists Protein tyrosine phosphatase-1b inhibitors Canitine-palmitoyltransferase-1 inhibitors Acetyl COA carboxylase-1 & -2 inhibitors Glucagon receptor antagonists Salicylate derivatives Immunomodulatory drugs

18 Case 3- A 35 y.o. caucasian male, obese since childhood, BMI 38, NASH, hypertensive, A1c-12.2, on metformin, SU All the following are reasonable except: Vegan diet Add TZD Add insulin Add SGLT-2 inhibitor Add GLP1-R agonist Refer to bariatric surgery

19 Change in body weight with longacting GLP-1R agonists **P < 0.001; ***P < Garber AJ. Diabetes Care 2011; 34(Suppl 2):S279-84

20 Efficacy of GLP-1R Agonists *P < 0.01 vs. comparator; **P < 0.001; ***P < ; ###P < vs. placebo Garber AJ. Diabetes Care 2011; 34(Suppl 2):S279-84

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22 Summary Non-insulin hypoglycemics can be used effectively to control T2DM Drug selection should be individualized, based on: age, cost, weight, risk of hypoglycemia Efficacy/Extent of hyperglycemia Pathophysiology/mechanism Disease duration Combination of agents with different mechanisms of action ADD, DO NOT SWITCH