The Changing Landscape of Diabetes Therapy for Cardiovascular Risk Reduction Paull Rukavina RPh MTM provider Fairview Apple Valley and Highland Park Clinics OBJECTIVES 1 Review ADAAACE Glycemic control Algorithms ID: 766847
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The Changing Landscape of Diabetes Therapy for Cardiovascular Risk Reduction Paull Rukavina, RPh. MTM provider - Fairview Apple Valley and Highland Park Clinics
OBJECTIVES: 1. Review ADA/AACE Glycemic control Algorithms. 2. Review CV trials/benefits of newer Type-2 Anti-Diabetic Medications (ADMs). 3. Discuss clinical pearls of newer Type-2 ADMs.
Previous DM Trials: Requirement of CV trials after Rosiglitazone Meta-Analysis: The FDA issued guidance in 2008 to ensure that new diabetes therapies were not associated with an unacceptable increase in CV risk. Type-2 DM is a major risk factor for CVD, the most common cause of death in Type-2 DM. At least 68% of people age 65 or older with diabetes die from some form of heart disease; and 16% die of stroke. Adults with diabetes are 2-4 times more likely to die from heart disease than adults without diabetes. Metformin shown in UKPDS trial (1998) to have CV benefit. Advance, VADT, and Accord Trials all showed A1c reduction with older diabetes medications (SFU’s, Insulins, TZD’s). Despite this there was not a significant reduction in CV outcomes and even in the Accord A1c-intensive treatment group (A1c 6.4%) had increased all cause mortality.
Glucagon-Like Peptide-1 receptor agonists: work on incretin hormones in GI tract and receptors in hypothalamus SGLT-2: work in proximal tubule of the kidney
Insulins and Sulfonyureas :
N=7,020 Median follow-up: 3.1 years Adults with Type-2 DM and known CVD Mean age: 63 years, baseline A1c 8.1% Primary outcome: 3 Point MACE- CV Death ,Non-fatal MI, Non-fatal stroke.
14% reduction in non-fatal MI, non-fatal stroke, CV death 32% reduction in death from any cause 35% reduction in hospitalization from heart failure 38% reduction in CV death
N=10,142 Median follow-up: 5.7 years, 2.1 years (Renal ) Patients with Type-2 DM and CVD or High Risk for CVD Mean Age 63 years, Baseline A1c 8.2% Primary Outcome: 3 Point MACE (CV Death, non-fatal MI, non-fatal stroke)
33% reduction in heart failure hospitalizations
N=17,160 Median follow-up 4.2 years Co-Primary Outcome: MACE and composite of CV death or hospitalization for heart failure. 60% of patients were primary prevention
N = 9,340, Mean age 63, Baseline A1c 8.7% Median follow-up 3.8 years, Median dose 1.8mg./day. Patients with Type-2 DM and CVD or High Risk for CVD Primary outcome: 3 point MACE-CV Death, non-fatal MI, non-fatal stroke
N=3,297, Mean Age 62 years, Baseline A1c 8.7% Median follow-up 2.1 years. Randomised dose either 0.5 or 1.0mg./week. Individuals with Type-2 DM and CVD(83%) or High Risk for CVD Primary outcome: 3 point MACE (CV Death, non-fatal MI, non-fatal Stroke)
26% Reduction 39% Reduction
N= 9901, mean age= 66 years old , Baseline A1c = 7.3% , 46.3% women Median follow-up 5.4 years , Dulaglutide dose 1.5mg./week. Individuals at least 50 years of age with Type-2 DM who either had a previous CV event (31.5%) or CV risk factors (68.5%) . (Primary prevention trial). Primary outcome: 3 point MACE (Non-fatal MI, Non-fatal stroke, CV death) Five-Year REWIND Results Show Sustained Dulaglutide CV Benefits
Summary: Victoza(3 pt. MACE-MI,Stroke,Death), Jardiance(CV death), Invokana(3 pt. MACE) have FDA approval for improving CV outcomes based on CVOTs. Only 3 newer DM meds with this indication/approval. Newer unpublished CVOT trial: Watch for Pioneer-6 trial -Oral Semaglutide trial. Not yet FDA approved. Obese Type 2 - My favorite DM algorithm: met + glp-1 + sglt-2 SGLT-2s work independent of beta-cell function or insulin resistance GLP-1’s -excellent for “grazer” type of DM patient. GLP-1’s - +non-fatal stroke decrease, SGLT-2’s= +Decrease Hosp.-HF
References: Association of second-line ADM’s with CV events among insured adults with Type-2 Diabetes. Jama Network Open (Diabetes and Endocrinology),December 21,2018. Rx Consultant: New considerations in Diabetes management , October 2018 The 2018 ACC Expert Consensus Statement outlines how to effectively manage patients with established cardiovascular disease and type 2 diabetes. NEJM Sglt-2 and Glp-1 trials 2015-2018. Rewind trial-Lancet 6-10-19.