PANCE - Diabetes Mellitus Treatments

Here are key facts for PANCE 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 and necessity: Insulin has the highest efficacy – this makes sense, since insulin deficiency is the root of the pathology in diabetes mellitus. 2. Type 1 management: Insulin is a required treatment and must be taken regularly throughout the day, with special considerations given to infection and surgery. 3. 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. 4. Formulation knowledge: Rapid, regular (or "short"), intermediate, and long-acting versions of insulin that are given in different patient scenarios. 5. Renal dosing: Give lower doses of insulin when a patient's estimated GFR is low. 1. First-line status: Metformin is first-line therapy in patients with Type 2 diabetes. 2. Mechanism of action: Metformin is a highly effective drug that reduces hepatic gluconeogenesis as a means of reducing blood glucose levels. 3. Safety profile: It does not cause hypoglycemia. 4. 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 effects: Side effects include gastrointestinal issues (nausea, vomiting), and there is potential for vitamin B12 deficiency. 1. Mechanism: 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 benefits: Empagliflozin, canagliflozin and dapagliflozin have beneficial effects on ASCVD, Heart Failure, and diabetic kidney disease. 3. Perioperative considerations: SGLT-2 inhibitors should be discontinued prior to surgery to avoid diabetic ketoacidosis. 4. Renoprotective effects: It is also thought that SGLT-2 inhibitors protect the kidneys via reductions in renal blood flow, glomerular hyperfiltration, and intra-glomerular pressure. 5. Adverse effects: Weight loss, bone fractures, urogenital infections, volume depletion and hypotension, increases in LDL levels, and increased risk of Fournier's gangrene and necrosis of the lower limb leading to foot and leg amputation. 1. Mechanism: 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 benefits: They also aid with appetite control and inhibition of glucagon secretion. 3. Cardiovascular benefits: Dulaglutide, liraglutide, and semaglutide have protective effects against ASCVD and diabetic kidney disease. 4. Administration routes: Administration can be subcutaneous injection or orally. 5. Adverse effects: They are associated with weight loss and gastrointestinal side effects. These drugs are associated with increased risk of acute pancreatitis.

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1. Type 2 considerations: 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. 2. Hypoglycemia risk: Insulin has potential hypoglycemic effects; the risk is higher when human insulin is used. 3. Side effect management: Weight gain is a common side effect of insulin use. 4. Cost barriers: 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. Mechanism of action: 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. Hypoglycemia risk: Because sulfonylureas increase insulin release, they can cause hypoglycemia. 3. Cardiovascular profile: They have neutral effects on ASCVD, heart failure, and diabetic kidney disease. 4. Adverse effects: 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. 5. Cost consideration: Cost is relatively low. 1. Mechanism of action: These drugs increase incretin levels, which increases insulin secretion. DPP-4 is an enzyme that otherwise breaks down incretins. 2. Efficacy: Intermediate efficacy. 3. Safety profile: No hypoglycemic effects. 4. Cardiovascular considerations: Saxagliptin is associated with an increased risk of heart failure. Renal disease effects are neutral. 5. Administration and cost: Indicate that administration is orally, and cost is high. 6. Adverse effects: Associated with Pancreatitis. 1. Mechanism of action: Highly effective drugs that improve insulin sensitivity, increase fatty acid uptake, and promote adipogenesis. 2. Safety profile: No hypoglycemic effects. 3. Contraindications: They are associated with increased risk of heart failure, and can cause fluid retention; thus, do not give to patients with renal impairment. 4. Administration and cost: Oral administration. Relatively low. 5. Adverse effects: These drugs are associated with weight gain, bone fractures, bladder cancer, increased LDL, and, as mentioned fluid retention.

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Below is information not explicitly contained within the tutorial but important for PANCE. 1. Medication selection algorithm: Understanding the ADA/EASD consensus algorithm for personalized diabetes management. 2. Combination therapy: Rational selection of medications with complementary mechanisms when monotherapy insufficient. 3. Step-up vs. step-down approaches: When to start with combination therapy vs. sequential addition. 1. History and physical exam pearls: Key questions and findings in diabetic patients on different medications. 2. Laboratory monitoring: Appropriate frequency for A1C, renal function, lipids, and other parameters. 3. Screening for complications: Evidence-based schedules for retinopathy, nephropathy, and neuropathy screening. 1. Geriatric considerations: Modified A1C targets, deintensification strategies, and avoiding hypoglycemia. 2. Pregnancy management: Contraindications for oral agents, insulin management, and increased monitoring frequency. 3. Pediatric Type 2 diabetes: Limited medication options and emphasis on lifestyle modifications. 1. Hypoglycemia management: Recognition, treatment protocols, and prevention strategies. 2. DKA vs. HHS: Differential diagnosis, fluid management, and insulin protocols. 3. Sick day rules: Medication adjustments during acute illness to prevent complications. 1. Shared decision making: Strategies for involving patients in treatment decisions. 2. Health literacy considerations: Assessing comprehension and tailoring education. 3. Team-based care: Coordinating with diabetes educators, nutritionists, and specialists.