USMLE/COMLEX 1 - Diabetes Mellitus Treatments

Here are key facts for USMLE Step 1 & COMLEX-USA Level 1 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. Highest efficacy: "Insulin has the highest efficacy – this makes sense, since insulin deficiency is the root of the pathology in diabetes mellitus." 2. Mechanism: "Insulin allows glucose uptake and utilization in key tissues." 3. Administration routes: "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. Types: "Rapid, regular (or "short"), intermediate, and long-acting versions of insulin that are given in different patient scenarios." 5. Key adverse effect: "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. Mechanism: "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. Efficacy: "Second generation sulfonylureas are highly effective drugs." 2. 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." 3. Hypoglycemia risk: "Because sulfonylureas increase insulin release, they can cause hypoglycemia." 4. Administration: "Oral administration." 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. Efficacy: "Intermediate efficacy." 3. Cardiovascular benefits: "Empagliflozin, canagliflozin and dapagliflozin have beneficial effects on ASCVD, Heart Failure, and diabetic kidney disease." 4. Safety profile: "They do not produce hypoglycemia." 5. Surgical considerations: "SGLT-2 inhibitors should be discontinued prior to surgery to avoid diabetic ketoacidosis."

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1. Type 1 requirement: "Insulin is a required treatment and must be taken regularly throughout the day, with special considerations given to infection and surgery." 2. Type 2 use: "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. Dosing considerations: "Give lower doses of insulin when a patient's estimated GFR is low." 4. Side effects: "Weight gain is a common side effect of insulin use." 5. Cost factors: "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." 1. Cardiovascular effects: "Metformin seems to have beneficial effects on cardiovascular outcomes, though more conclusive studies are needed." 2. Administration route: "This drug is administrated orally." 3. Cost advantage: "It is relatively low in cost." 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. They also aid with appetite control and inhibition of glucagon secretion." 2. Cardiovascular benefits: "Dulaglutide, liraglutide, and semaglutide have protective effects against ASCVD and diabetic kidney disease." 3. Safety profile: "No hypoglycemic effects." 4. Administration options: "Administration can be subcutaneous injection or orally." 5. Side effects: "They are associated with weight loss and gastrointestinal side effects. These drugs are associated with increased risk of acute pancreatitis." 1. Mechanism: "These drugs increase incretin levels, which increases insulin secretion. DPP-4 is an enzyme that otherwise breaks down incretins." 2. Efficacy: "Intermediate efficacy." 3. Cardiovascular considerations: "Saxagliptin is associated with an increased risk of heart failure. Renal disease effects are neutral." 4. Administration and cost: "Indicate that administration is orally, and cost is high." 5. Side effects: "Associated with Pancreatitis." 1. Mechanism: "Highly effective drugs that improve insulin sensitivity, increase fatty acid uptake, and promote adipogenesis." 2. Safety profile: "No hypoglycemic effects." 3. Cardiovascular risk: "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. Side effects: "These drugs are associated with weight gain, bone fractures, bladder cancer, increased LDL, and, as mentioned fluid retention."

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1. Pharmacokinetics: Different insulin types have unique onset, peak, and duration profiles critical for exam questions. 2. Insulin resistance: Important concept in Type 2 diabetes pathophysiology affecting insulin dosing. 3. C-peptide measurements: Help differentiate Type 1 from Type 2 diabetes by indicating endogenous insulin production. 1. Mechanism details: Activates AMP-activated protein kinase (AMPK) pathway. 2. Contraindication expansion: Avoid in hepatic impairment, alcoholism, and conditions predisposing to hypoxia. 3. Low risk of hypoglycemia: Important distinguishing feature explained by its insulin-sensitizing rather than insulin-stimulating mechanism. 1. Mechanism of action details: SGLT-2 transporters reabsorb approximately 90% of filtered glucose in the proximal tubule. 2. Euglycemic DKA: Unique complication to recognize in exam vignettes involving SGLT-2 inhibitors. 3. Urinary tract infections: More common in women due to glucosuria promoting bacterial growth. 1. GLP-1 vs. DPP-4: Both affect incretin pathway but through different mechanisms - direct agonism vs. prevention of breakdown. 2. Incretin physiology: Enteroendocrine L-cells in intestine release GLP-1 in response to food intake. 3. Half-life considerations: Native GLP-1 has extremely short half-life (1-2 minutes), which is why DPP-4 inhibition or GLP-1 analogs are necessary for therapeutic effect. 1. Hypoglycemia risk: Significantly increases when combining insulin with sulfonylureas. 2. Metformin-related: May decrease B12 absorption; important to monitor levels in long-term use. 3. Multiple drug regimens: Step-wise approach typically starting with metformin and adding second agent based on patient characteristics.