AACE/ACE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM. Sherwin D Souza, MD, FACE

Transcription

1 AACE/ACE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM Sherwin D Soza, MD, FACE

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8 Prediabetes Treatment Algorithm T2DM = type 2 diabetes mellits BP = blood pressre CVD = cardiovasclar disease TZD = thiazolidinedione GLP-1 RA= glcagon-like peptide-1 receptor agonist Weight-loss agents orlistat, lorcaserin, and phentermine/topiramate can prevent progression to T2DM Improve BP, triglycerides, and inslin sensitivity Metformin and acarbose can redce progression to T2DM by 25% - 30% Use for prediabetes is off-label Both are safe, confer CVD risk benefit; metformin is well tolerated TZDs prevented progression to T2DM in 60% - 75% of patients in clinical trials Associated with adverse otcomes GLP-1 receptor agonists may be as effective as TZDs Promote weight loss, bt inadeqate safety data TZDs and GLP-1 RAs reserved for patients not responding to conventional therapies or at highest risk for T2DM AACE Comprehensive Diabetes Management Algorithm Endocr Pract. 2013;19(3):

9 The Ticking Clock Increased risk for both microvasclar and macrovasclar disease begins early in the prediabetic state -Inslin resistance is already present in patients with NGT who later develop T2DM -Patients with prediabetes already have high inslin resistance and significantly decreased beta-cell fnction -Both diabetic retinopathy, peripheral neropathy, and nephropathy occr in patients with prediabetes -Patients with prediabetes have a 2 to 3-fold increase in CHD risk, similar to patients with diabetes CHD = coronary heart disease; NGT = normal glcose tolerance; T2DM = type 2 diabetes mellits AACE Comprehensive Diabetes Management Algorithm Endocr Pract. 2013;19(3): ; DeFronzo RA et al. Am J Cardiol. 2011;108(3 Sppl):3B-24B

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12 Risk of Hypoglycemia Plays a significant role in choice of agents in AACE algorithm For patients at highest risk of hypoglycemia, may consider close evalation of agents chosen as well as therapetic goal Patients with type 2 diabetes at highest risk of low blood glcose inclde those with: Diabetes dration >15 years Advanced macrovasclar disease Hypoglycemia nawareness Limited life expectancy Severe comorbidities AACE Comprehensive Diabetes Management Algorithm Endocr Pract. 2013;19(3): ; AACE Algorithm for Glycemic Control, Endocr Pract. 2009;15(6):

13 AACE Comprehensive Diabetes Management Algorithm Endocr Pract. 2013;19(3): Sitagliptin [package insert]. Whitehose Station, NJ; Merck Co. Inc.; Saxagliptin [package insert]. Princeton, NJ; Bristol Meyers Sqibb; 2009; Linagliptin [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceticals Clinical Considerations Combining therapetic agents with different modes of action may be advantageos Use inslin sensitizers sch as metformin and/or TZDs as part of the therapetic regimen in most patients (nless contraindicated or intolerance to these agents has been demonstrated) Inslin and secretagoges are the only medications that case significant hypoglycemia Therefore, dosage of secretagoges or inslin shold be adjsted as blood glcose levels decline, when sed in combination with metformin, TZD, DPP-4 inhibitors, and/or incretin mimetics (GLP-1 agonists) TZD = thiazolidinediones; DPP-4 = dipeptidyl peptidase-4; GLP-1 = glcagon-like peptide-1

14 Effect of Glcose-lowering Drgs on Patient Weight Therapetic Options Slfonylrea 1,2 Weight TZD 3,4 Inslin 5,6 Metformin 7 DPP-4 inhibitor 8 GLP-1 receptor agonist 9 SGLT-2 Inhibitors 10 A1C = glycated hemoglobin; DPP-4 = dipeptidyl peptidase-4; GLP-1 = glcagon-like peptide-1; SGLT-2 = sodim glcose co-transporter-2; TZD = thiazolidinedione 1. Malone M. Ann Pharmacother. 2005;39: Glipizide [package insert]. New York, NY; Pfizer; Pioglitazone [package insert]. Deerfield, IL: Takeda Pharmaceticals America; Rosiglitazone [package insert]. Research Triangle Park, NC; GlaxoSmithKline; Nathan DM, et al. Diabetes Care. 2008;31(1): Holman RR. NEJM. 2007;357(17): Metformin[package insert]. Princeton NJ; Bristol Meyers Sqibb; Sitagliptin [package insert].

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16 -Metformin 1 st choice (if no contraindication) -Consider drgs in the order sggested -Order of medications represents a sggested hierarchy of sage -Length of line reflects strength of recommendation -SFU s are lowest on the list (Short-lived effect, strong risk of hypoglycemia that may increase hospitalizations in elderly patients, may increase MI risk, contraindicated for patients with renal failre) -If nsccessfl, move to dal oral rx Metformin still cornerstone of therapy (If contraindicated, consider TZD as fondation of rx) Road Map to Achieve Glycemic Goals A1c < 7.5%

17 Dal therapy with metformin provides sperior glycemic control over metformin alone. If dal oral Rx is sccessfl, consider triple therapy If triple oral rx fails to achieve A1C goal, initiate inslin AA A1c 7.5-9% Road Map to Achieve Glycemic Goals

18 Algorithm to Achieve Glycemic Goals Baseline A1C > 9.0% If patient is asymptomatic with recent onset of disease and drg naïve, may consider starting with dal or triple oral regimens If symptomatic, start inslin Once A1C has improved to <7.5%, consider initiation of dal oral therapy with tapering and possible discontination of inslin rx AACE Comprehensive Diabetes Management Algorithm Endocr Pract. 2013;19(3):

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22 UKPDS: Benefits of Glycemic Control Every 1% decrease in A1C led to significant redctions in diabetes-related complications 14% 21% 37% 43% Risk of myocardial infarction Risk of diabetesrelated death Risk of microvasclar complications Risk of amptation or PVD Death Decrease was statistically significant for all comparisons shown Stratton IM et al. BMJ. 2000;321:

23 Landmark Glycemia Trials Action to Control Cardiovasclar Risk in Diabetes (ACCORD) Action in Diabetes and Vasclar Disease Preterax and Diamicron MR Controlled Evalation (ADVANCE) Veterans Affairs Diabetes Trial (VADT) All condcted in: Older patients ( 60 years of age) Patients with cardiovasclar disease (CVD; 1/3 to 1/2 of cohorts) or 1 CVD risk factors Ray et al. Lancet. 2009;373:

24 Probability of All-case Mortality with Intensive Glcose-lowering vs. Standard Treatment All-case mortality Ray et al. Lancet. 2009;373:

25 EMPA REG(empagliflozin) Empagliflozin is the first SGLT2 inhibitor to report CV benefit 14% redction in the hazard of MACE in over 7000 patients with T2DM + CVD 38% redction in CV mortality Heart failre hospitalization was redced by 38% Also shown to have renal benefits: 39% decrease in pre specified end points(progression to macroalbminria, dobling of serm Cr, worsening nephropathy, initiation of renal replacement therapy).

26 LEADER-Trial (Liragltide) Liragltide is the second Drg to show CV benefits 13% lower risk of primary composite MACE otcome 22% lower risk of CV mortality 15% lower risk of all case mortality 15% lower risk of microvasclar (renal events-driven mainly by redction in macroalbminria)

27 CVOT s-smmary Empagliflozin has an FDA indication to redce the risk of cardiovasclar death in adlt patients with type 2 diabetes mellits and cardiovasclar disease. On 8/25/17, FDA approved a new indication for Victoza (liragltide) to redce the risk of major adverse cardiovasclar (CV) events, heart attack, stroke and CV death, in adlts with type 2 diabetes and established CV disease Weigh the risk vs benefits of all antihyperglycemic agents before prescribing. ADA 2017 and AACE/ACE 2017 gidelines now inclde recommendations for considerations of empagliflozin or liragltide in patients with T2 DM not at goal and established atherosclerotic CVD.

28 CVOT s and Diabetes in some takeaways.. Based on recent CVOT s, the manner in which glcose is lowered is more important than the degree of glcose lowering. Shold we be sing therapies proven to redce CV events in those with pre-existing CVD? In those withot CVD and mild hyperglycemia, DPP-4 inhibitors may be reasonable options. Pioglitazone has limited se bt can be considered in the very inslin resistant patient with no major risks of HF

29 CVOTs and Diabetes in any takeaways? Slfonylreas cold be sed selectively in those with intact renal fnction possibly third line in those not able to se the other agents(avoid in elderly) If the HbA1c is very high, inslin therapy remains the most efficacios therapy as long as the dose is appropriately titrated. COST remains the major isse with branded medications and of corse this aspect mst be taken into accont.

30 Thanks for yor attention!