ABIM - Diabetes Mellitus Treatments

Here are key facts for ABIM from the Diabetes Mellitus - Pathophysiology tutorial, as well as points of interest at the end of this document that are not directly addressed in this tutorial but should help you prepare for the boards. See the tutorial notes for further details and relevant links.

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1. Efficacy rationale: Insulin has the highest efficacy – this makes sense, since insulin deficiency is the root of the pathology in diabetes mellitus. 2. Renal considerations: Give lower doses of insulin when a patient's estimated GFR is low. 3. Clinical application: Insulin is a required treatment and must be taken regularly throughout the day, with special considerations given to infection and surgery. 4. Treatment progression: These patients may not need insulin if their glucose levels are controlled by other medications and/or changes in diet and exercise. However, when glucose targets are not met by these measures, patients will need insulin. 5. Risk assessment: Insulin has potential hypoglycemic effects; the risk is higher when human insulin is used. 1. First-line rationale: Metformin is first-line therapy in patients with Type 2 diabetes. 2. Pharmacologic mechanism: Metformin is a highly effective drug that reduces hepatic gluconeogenesis as a means of reducing blood glucose levels. 3. Cardiovascular impact: Metformin seems to have beneficial effects on cardiovascular outcomes, though more conclusive studies are needed. 4. Critical contraindication: Metformin doesn't seem to affect the development of chronic kidney disease, but is contraindicated in patients with low estimated GFR (eGFR < 30 mL/min/1.73m²). 5. Side effect profile: Side effects include gastrointestinal issues (nausea, vomiting), and there is potential for vitamin B12 deficiency. 1. Mechanism and action: These drugs decrease blood glucose levels by increasing glucose output in the urine. They do this by inhibiting the sodium-glucose co-transports and blocking glucose reabsorption in the nephron. 2. Cardiovascular evidence: Empagliflozin, canagliflozin and dapagliflozin have beneficial effects on ASCVD, Heart Failure, and diabetic kidney disease. 3. Cardioprotective mechanisms: Cardioprotective effects include reducing blood pressure, producing osmotic diuresis, and improving cardiac energy metabolism, among others. 4. Renoprotective mechanisms: It is also thought that SGLT-2 inhibitors protect the kidneys via reductions in renal blood flow, glomerular hyperfiltration, and intra-glomerular pressure. 5. Perioperative risk: SGLT-2 inhibitors should be discontinued prior to surgery to avoid diabetic ketoacidosis. 1. Mechanism and efficacy: Highly effective drugs that increase insulin secretion by stimulating receptors for Glucagon-Like-Peptide-1, which is an incretin that facilitates pancreatic release of insulin. 2. Multiple therapeutic effects: They also aid with appetite control and inhibition of glucagon secretion. 3. Cardiovascular outcomes: Dulaglutide, liraglutide, and semaglutide have protective effects against ASCVD and diabetic kidney disease. 4. Risk monitoring: These drugs are associated with increased risk of acute pancreatitis. 5. Weight management benefit: They are associated with weight loss and gastrointestinal side effects.

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1. Formulation considerations: Rapid, regular (or "short"), intermediate, and long-acting versions of insulin that are given in different patient scenarios. 2. Administration options: Insulin is often administered into subcutaneous tissues via injections or continuously via an insulin pump; an inhaled version with rapid action can be used before meals. 3. Weight impact: Weight gain is a common side effect of insulin use. 4. Access considerations: In the US, especially, the price of insulin is an impediment to proper diabetes management. Cost varies by type of insulin and route of administration; for simplicity, indicate that human insulin costs less than analog insulin. 1. Cellular mechanism: They increase insulin secretion via beta cell stimulation. They do this by interacting with the sulfonylurea receptors, which reduce cellular potassium release; this depolarizes the cell and triggers insulin release. 2. Clinical efficacy: Second generation sulfonylureas are highly effective drugs. 3. Hypoglycemia risk: Because sulfonylureas increase insulin release, they can cause hypoglycemia. 4. Cardiovascular neutrality: They have neutral effects on ASCVD, heart failure, and diabetic kidney disease. 5. Long-term risks: These drugs can cause weight gain (like insulin does), and, despite being the second most prescribed drug for diabetes treatment, these drugs are associated with increased risk of cardiovascular event and mortality. 1. Pharmacologic mechanism: These drugs increase incretin levels, which increases insulin secretion. DPP-4 is an enzyme that otherwise breaks down incretins. 2. Efficacy classification: Intermediate efficacy. 3. Safety advantage: No hypoglycemic effects. 4. Specific cardiac risk: Saxagliptin is associated with an increased risk of heart failure. 5. Renal impact: Renal disease effects are neutral. 6. Serious adverse effect: Associated with Pancreatitis. 1. Cellular action: Highly effective drugs that improve insulin sensitivity, increase fatty acid uptake, and promote adipogenesis. 2. Safety profile: No hypoglycemic effects. 3. Cardiac contraindication: They are associated with increased risk of heart failure, and can cause fluid retention; thus, do not give to patients with renal impairment. 4. Comprehensive risk profile: These drugs are associated with weight gain, bone fractures, bladder cancer, increased LDL, and, as mentioned fluid retention. 5. Practical considerations: Oral administration. Relatively low cost.

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1. Guideline-directed therapy: Critical interpretation of ADA/EASD joint consensus statements with focus on cardiovascular risk reduction. 2. Landmark clinical trials: Understanding key studies that shaped current diabetes management (EMPA-REG, CANVAS, LEADER, SUSTAIN-6, DCCT/EDIC). 3. Comparative effectiveness: Relative benefits of newer antihyperglycemic agents versus established therapies in various patient populations. 1. Cardiorenal axis: Selecting agents based on heart failure (HFrEF vs HFpEF), chronic kidney disease stage, and albuminuria status. 2. Hepatic impairment: Medication adjustments in NAFLD/NASH and cirrhosis. 3. Advanced atherosclerotic disease: Balancing glycemic targets with secondary prevention strategies. 1. Inpatient glycemic control: Critical care and non-critical care protocols, transition from IV to subcutaneous insulin. 2. Perioperative management: Risk stratification and medication adjustment protocols. 3. Brittle diabetes: Identification and management strategies for glucose variability. 1. Insulin resistance syndromes: Recognition and targeted approaches beyond conventional diabetes therapy. 2. Secondary diabetes: Management differences in pancreatic, endocrine, and drug-induced hyperglycemia. 3. Hypoglycemia unawareness: Risk factors, detection, and prevention strategies. 1. Diabetes care metrics: Understanding HEDIS measures and quality reporting requirements. 2. Team-based care models: Effective collaboration with diabetes educators, pharmacists, and specialists. 3. Outpatient insulin management programs: Design and implementation of safe titration protocols.