USMLE/COMLEX 2 - Diabetes Mellitus Treatments

Here are key facts for USMLE Step 2 & COMLEX-USA Level 2 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. Clinical necessity in Type 1: Insulin is a required treatment and must be taken regularly throughout the day, with special considerations given to infection and surgery. 2. Type 2 diabetes application: 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. 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. Dosage considerations: Give lower doses of insulin when a patient's estimated GFR is low. 5. Monitoring requirement: Insulin has potential hypoglycemic effects; the risk is higher when human insulin is used. 1. First-line status: Metformin is first-line therapy in patients with Type 2 diabetes. 2. Safety profile advantage: It does not cause hypoglycemia. 3. 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). 4. Patient counseling: Side effects include gastrointestinal issues (nausea, vomiting), and there is potential for vitamin B12 deficiency. 1. Preoperative management: SGLT-2 inhibitors should be discontinued prior to surgery to avoid diabetic ketoacidosis. 2. Cardiovascular benefits: Empagliflozin, canagliflozin and dapagliflozin have beneficial effects on ASCVD, Heart Failure, and diabetic kidney disease. 3. Renal protection mechanism: It is also thought that SGLT-2 inhibitors protect the kidneys via reductions in renal blood flow, glomerular hyperfiltration, and intra-glomerular pressure. 4. Serious 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. Clinical 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 mechanisms: They also aid with appetite control and inhibition of glucagon secretion. 3. Cardiovascular protection: Dulaglutide, liraglutide, and semaglutide have protective effects against ASCVD and diabetic kidney disease. 4. Patient monitoring: These drugs are associated with increased risk of acute pancreatitis.

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1. Cost considerations: Cost varies by type of insulin and route of administration; for simplicity, indicate that human insulin costs less than analog insulin. In the US, especially, the price of insulin is an impediment to proper diabetes management. 2. Adverse effect management: Weight gain is a common side effect of insulin use. 3. Formulation selection: Rapid, regular (or "short"), intermediate, and long-acting versions of insulin that are given in different patient scenarios. 1. Potential added benefit: Metformin seems to have beneficial effects on cardiovascular outcomes, though more conclusive studies are needed. 2. Cost-effectiveness: It is relatively low in cost. 3. Patient adherence: This drug is administrated orally. 1. Mechanism relevant to management: 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 considerations: They have neutral effects on ASCVD, heart failure, and diabetic kidney disease. 4. Risk-benefit assessment: 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. Mechanism of action: These drugs increase incretin levels, which increases insulin secretion. DPP-4 is an enzyme that otherwise breaks down incretins. 2. Safety profile: No hypoglycemic effects. 3. Specific contraindication: Saxagliptin is associated with an increased risk of heart failure. 4. Adverse event monitoring: Associated with Pancreatitis. 1. Mechanism in practice: Highly effective drugs that improve insulin sensitivity, increase fatty acid uptake, and promote adipogenesis. 2. Contraindication: They are associated with increased risk of heart failure, and can cause fluid retention; thus, do not give to patients with renal impairment. 3. Cost advantage: Relatively low. 4. Comprehensive side effect profile: These drugs are associated with weight gain, bone fractures, bladder cancer, increased LDL, and, as mentioned fluid retention.

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1. Continuous glucose monitoring (CGM) systems can be paired with insulin pumps to create a closed-loop system for more precise management. 2. Sick day rules for insulin-dependent patients include never skipping doses and more frequent monitoring. 3. Dawn phenomenon: Morning hyperglycemia due to growth hormone surge; may require adjustment of overnight insulin regimen. 1. Lactic acidosis risk: Though rare, this is a medical emergency requiring immediate discontinuation. Risk factors include renal failure, severe illness, and alcohol abuse. 2. Preoperative management: Generally stopped 48 hours before procedures with contrast media. 3. PCOS treatment: Metformin is often used off-label for polycystic ovary syndrome to improve insulin sensitivity. 1. Tirzepatide: Newer GLP-1/GIP dual agonist showing superior glycemic control and weight loss compared to semaglutide. 2. Once-weekly GLP-1 formulations (semaglutide, dulaglutide) improving adherence compared to daily options. 3. Fixed-ratio combinations of GLP-1 agonists with insulin showing efficacy with fewer side effects. 1. Heart failure indications: Now approved for heart failure with reduced ejection fraction even in non-diabetic patients. 2. Euglycemic DKA: Can occur with normal blood glucose levels; important to recognize in acutely ill patients. 3. Triple therapy combinations with metformin and GLP-1 agonists showing synergistic effects with complementary mechanisms. 1. American Diabetes Association (ADA) algorithm recommends considering ASCVD, heart failure, and CKD status in medication selection. 2. Deprescribing considerations in elderly patients, especially those with frequent hypoglycemia. 3. Therapeutic inertia: Recognizing and overcoming delays in intensification of therapy when A1c targets aren't met.