Type 2 Diabetes: Where Do We Start with Treatment? DIABETES EDUCATION. Diabetes Mellitus: Complications and Co-Morbid Conditions

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2 Diabetes Mellitus: Complications and Co-Morbid Conditions ADA Guidelines for Glycemic Control: 2016 Retinopathy Between , 28.5% of patients with diabetes 40 years and older diagnosed with diabetic retinopathy Glycemic Targets Goals Nephropathy In 2011, 44% of all new cases of kidney failure were diabetes-related Hemoglobin A1C < 7.0%* Neuropathy / Amputations In 2011, 60% of nontraumatic lower-limb amputations were diabetes-related Pre prandial plasma glucose Peak postprandial plasma glucose mg/dl* < 180 mg/dl* American Diabetes Association, Fact Sheet 2014 Zoungas S & Patel A. Annals NYAS American Diabetes Association. Diabetes Care ACCORD: Intensive Glucose Management Increased Mortality Results Primary Endpoint: Non-fatal MI, Stroke and death from CV causes was non-significant Secondary Endpoint: Increased mortality in intensively treated (HR 1.22, p=0.04) ADA Recommendations: Non-Pregnant Adults with Diabetes *Goals Should Be Individualized Based on: Duration of diabetes Individual patient considerations Co morbid Conditions Known CVD or advanced microvascular complications (A1C < 7.5%) Hypoglycemia unawareness Age & Health Status (<7.5 to 8.5%) ACCORD Study Group. NEJM 2008 American Diabetes Association. Diabetes Care Diabetes Goals in Older Adults: A Consensus Report by the ADA and AGS Health Status A1C Goal Healthy (Few coexisting chronic illnesses, intact cognitive and functional status) < 7.5% Intermediate (Multiple coexisting chronic illnesses or 2+ instrumental ADL impairments or mild/moderate cognitive impairment) < 8.0% Very Complex (Long term care, endstate chronic illness or moderate severe cognitive impairment) < 8.5% Type 2 Diabetes: Where Do We Start with Treatment? DIABETES EDUCATION Kirkman MS, et al. Diabetes Care and JAGS. 2012

3 Cochrane Review: Group Based Diabetes Education in People with T2DM Hemoglobin A1C Difference -1.4% -0.8% -1.0% Type 2 DM: What About Medications? Deakin T, et al. Cochrane Medications to Treat Type 2 Diabetes Mellitus Metformin vs. Metformin ER: Reduced GI Side Effects Metformin Metformin ER Adapted from Nathan D. N Engl J Med 2007;356: Type 2 Diabetes Medications Oral s T2DM: Sulfonylureas and Meglitinides Metformin Failure: What s Next? Sulfonylureas (glyburide, glipizide, glimepiride) Meglitinides (repaglinide, nateglidnide) -1 to 2% Binds sulfonylurea receptor on -cells, stimulates insulin -1 to 1.5% Binds sulfonylurea receptor on -cells, stimulates insulin Extensive experience, improved microvascular outcomes Short acting, targets postprandial glucose Hypoglycemia, weight gain Hypoglycemia, weight gain

4 Sulfonylureas and Meglitinides: DPP IV inhibitors An inexpensive, oral medication with a well-known risk profile. Relatively strong in its A1C lowering effect and has a higher risk of hypoglycemia Elderly or others at risk of hypoglycemia Erratic eating habits Beta cell mass preservation (not fully proven) Sitagliptin (Januvia) Saxagliptin (Onglyza) Linagliptin (Tradjenta) % Inhibit degradation of GLP-1 and GIP Minimal hypo risk No weight gain 1. Pancreatitis / Pancreatic CA (?) 2. Nasopharyngitis and UTI 3. Renal Adjustment except Linagliptin Alogliptin (Nesina) Kahn SE, et al. NEJM 2006 DPP IV Inhibitors = Pills DPP IV Inhibitors: GLP-1 Receptor Agonists An oral medication with a modest A1C lowering effect and no associated weight gain. There is no risk of hypoglycemia (elderly) and probably negligible other side effects. Those concerned about cost or theoretical risk of pancreatitis & pancreatic cancer Exenatide (Byetta) Liraglutide (Victoza) Exenatide LAR (Bydureon) % GLP-1 receptor agonist Minimal hypo risk Weight Loss 1. Nausea, diarrhea, vomiting 2. Acute pancreatitis / Pancreatic CA (?) 3. Acute renal failure 4. Thyroid C-Cell tumors 5. Contraindications: (a) Gastroparesis (b) Cr Clearance < 30 Albiglutide (Tanzeum) Dulaglutide (Trulicity) GLP-1 RA = Injectables 25 GLP-1 Receptor Agonists: Thiazolidinediones (TZDs) Those aiming for weight loss in addition to a relatively strong A1C lowering effect. Additionally, little to no hypoglycemia. Those concerned about cost (brand name), using an injectable medication or the possibility of pancreatitis & pancreatic cancer Pioglitazone (Actos) Rosiglitazone (Avandia) -1 to 2% Activates PPAR-, increase peripheral insulin sensitivity No Hypoglycemia Improves insulin sensitivity Possibly beta cell sparing 1. Edema 2. Weight gain 3. Fractures 4. Monitor LFTs 5. Symptomatic heart failure 6. Liver dysfunction 7. Bladder Cancer

5 Thiazolidinediones (TZD): Sodium Glucose Co-transporter 2 (SGLT2) Inhibitors In those wishing for a relatively strong A1C lowering effect from an oral medication without hypoglycemia. It is also low-cost. Who might not want to use this medication? In patients concerned about weight gain or at higher risk for heart failure, fracture risk. Dapagliflozin (Farxiga) Canagliflozin (Invokana) Empagliflozin (Jardiance) Mechanism of -0.5 to 1% Enhance renal glucose excretion No hypoglycemia Blood pressure reduction Weight neutral / weight loss Genitourinary Infections *Dapagliflozin use not recommend GFR < 60 *Canagliflozin use not recommend GFR < 45 (100 mg if GFR <60) SGLT2 Inhibitors: In patients looking for a pill that is relatively efficacious in A1C lowering without weight gain or hypoglycemia risk. Additionally, those looking for a positive CVD effect. Patients concerned about new medications without a long-term track record. Additionally, patients worried about the diuretic effect or GU infections. What Basal Insulin to add? NPH Glargine Detemir Glargine U300 Degludec