Initiating Injectable Therapy in Type 2 Diabetes David Doriguzzi, PA C Learning Objectives To understand current Diabetes treatment guidelines To understand how injectable medications fit into current treatment guidelines To understand the benefits vs risks of various injected diabetes medications To recognize when injected medications would be appropriate and beneficial To learn how to approach a patient with the suggestion of initiating injected therapy To be able to train a patient on proper injection technique and maintain patient compliance Current Guidelines AACE recommends an individualized regimen with a target Hemoglobin A1c < 6.5% for most patients. 1 ADA recommends a target hemoglobin A1c < 7.0%, but also stresses individualization depending on age and other risk factors. 2
Maintaining Control The UKPDS and the DCCT both showed that diabetes is progressive and patients will usually require escalation of therapy 3,4 Maintaining Control Maintaining Control The UKPDS and the DCCT both showed that diabetes is progressive and patients will usually require escalation of therapy 3,4 Most patients will require multiple medications over time to achieve and maintain goal. Beta cell decline commonly results in the eventual need for insulin 5
Clinical Inertia in Managing Diabetes Patients are commonly allowed to remain in poor glycemic control for several years before therapy is intensified. Clinicians wait an average of 6 years before initiating insulin therapy in patients with A1c > 8.0%. Khunti, et al. Diabetes Care. 36:3411 3417, 2013
Perfect Pills? Metformin nausea, diarrhea, contraindicated in chronic kidney disease Sulfonylureas hypoglycemia, weight gain, beta cell fatigue TZDs edema, weight gain, contraindicated in CHF DPP IV inhibitors nausea, concerns of pancreatitis SGLT2 inhibitors Urogenital mycotic infections, caution if used with ACE I or ARBs Barriers to Injected Therapy PATIENT CONCERNS Injected medications are temperature sensitive Patients might be required to carry injection supplies Performing an injection takes slightly more time than swallowing a pill Patients maybe reluctant to inject in public. Barriers to Injected Therapy PRESCRIBER CONCERNS Fear of inducing hypoglycemia Training patients to self inject takes time Lack of understanding of when injection initiation is appropriate 6 Managing patients on injectables (particularly insulin) can be complex & time consuming
Benefits of Injected Therapy No treatment is more effective than insulin in lowering extremely high glucose 7 Insulin dosing is highly customizable Weight loss associated with GLP 1 Analogues. Lower hypoglycemia associated with GLP 1 Analogues Available Injected Therapies GLP 1 Agonists Exenatide (Byetta) 5mcg 10 mcg BID Exenatide (Bydureon) 2 mg weekly Liraglutide (Victoza) 0.6 1.8 mg daily Dulaglutide (Trulicity) 0.75 1.5 mg weekly Albiglutide (Tanzeum) 30 50 mg weekly Lixisenetide (Adlyxin) 10 20 mg daily Activate GLP 1 receptors, increasing insulin sensitivity, increasing satiety, and increasing insulin production Available Injected Therapies Amylin Analogue Pramlintide (Symlin) 60 120 mg QAC Delays gastric emptying, decreases hepatic glucose production, increases insulin secretion Approved for Type 1 and Type II Diabetes
Available Injected Therapies INSULIN Long Acting Insulin Analogues Insulin Glargine (Lantus) Insulin Glargin U 300 (Toujeo) Insulin Detemir (Levemir) Insulin Degludec (Tresiba) INSULIN Available Injected Therapies Fast Acting Insulin Analogues Insulin lispro (Humalog) Insulin aspart (Novolog) Insulin glulisine (Apidra) INSULIN Available Injected Therapies Regular Human Insulin Humulin R (U 100, U 500) Novolin R Afrezza (Inhaled)
Available Injected Therapies INSULIN Intermediate Duration Insulin NPH (Humulin N, Novolin N) PREMIXED INSULIN Available Injected Therapies NPH/Regular Humulin 70/30, Novolin 70/30 Analogue Premixes Humalog Mix 75/25 Humalog Mix 50/50 Novolog Mix 70/30 Injection Issues GLP 1s: nausea, vomiting, diarrhea, pancreatitis, medullary thyroid CA in rodents (so far has never been observed in humans) Injection site subcutaneous nodules with Bydureon Insulin: weight gain, hypoglycemia, hypokalemia, injection site lipodystrophy Symlin: hypoglycemia, nausea, vomiting
When Is The Right Time? When Is The Right Time? When Is The Right Time? When additional OADs are contraindicated or poorly tolerated When additional OADs could present undesirable effects (e.g. weight gain) When treatment with multiple OADs have failed Any time the hemoglobin A1c > 9% and the patient is symptomatic insulin should be considered
Choosing The Best Option If A1c is less than 9% and weight gain is a concern, GLP 1 is a viable choice 9 If compliance is an issue, weekly injections simplify dosing 10 GLP 1s are associated with less hypoglycemia than insulin (or even sulfonylureas) If hyperglycemia is severe or if the patient is symptomatic, Insulin is the best choice Considering The Patient The patient should be agreeable to injection therapy to reduce non compliance The patient should be mentally/physically able to self inject, or have a reliable support system for administration of injections Accidental non compliance (skipped doses) is twice as frequent in elderly patients. 8 The patient should have an adequate understanding of how and when the injections are to be administered Present all reasonable options to the patient, explaining advantages and disadvantages of each. Pitching the Plan When properly educated about medication choices, many patients will actually choose the injectable option. Patient compliance is much likely to be higher if he/she feels part of the decisionmaking process
Improving Compliance Providing injection training in the office decreases patient apprehension and allow the opportunity for the patient to ask questions Staff members/mas can assist in providing training If available, CDEs can provide excellent injection training and diet education Retrain if necessary Where to Start If starting a GLP 1, start at the lowest recommended dose (5 mcg for Byetta, 0.6 mg for Victoza) and titrate up as needed, usually after 1 month. If starting basal insulin, start at a relatively low dose and gradually titrate up. Patient self titration vs guided titration If using multiple daily injections, total daily dose should generally be 50% basal, 50% bolus Maintaining Control Regular dialogue with the patient is necessary to fully evaluate the situation Review logbooks and diaries Food diaries assist in determining whether diet improvement or medication increase is indicated Ask about medication compliance prior to assuming medication failure
Maintaining Control Adjustments may be necessary with time as diabetes progresses Insulin titrations are often required with changes to BMI, work schedules, lifestyle Patients can be taught to self titrate basal insulin GLP 1 doses can be progressively increased Sample Patient 1 46 year old overweight female (BMI 32.6) with a 5 year history of Type 2 diabetes. Currently taking Metformin 1000 mg BID and Januvia 100 mg QD. Vitals are normal Hemoglobin A1c is now 7.7%. Fasting BG average is 156 and postprandial BG average is 201 mg/dl. Has been trying to improve diet and exercises on occasion. In spite of this, she has gained 3 lbs since her last visit. Sample Patient 2 68 year old male with an 11 year history of Type 2 diabetes. Currently taking metformin 1000 mg BID and glimepiride 4 mg BID. Vitals are normal Hemoglobin A1c is 8.8%. Fasting BG average is 152 and postprandial BG average is 188 mg/dl. Has also has a history of CHF, HTN, hyperlipidemia, and chronic pancreatitis due to previous alcoholism
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