Diabetes Pharmacology

Case 1 (New diagnosis). A 54-year-old man presents with polyuria and fatigue. BMI 35. BP 142/88. A1C 9.4%. eGFR 82. No known ASCVD, HF, or CKD. What is the best initial pharmacologic strategy?

Case 1 (3 months later). He is on maximally tolerated metformin (Glucophage) + semaglutide (Ozempic). A1C is 8.8%. He has no HF/CKD/ASCVD and wants the next step with the best weight profile. Which option is best to add?

Case 1 (1 year later). He develops symptomatic HFrEF (EF 35%). Current meds: metformin (Glucophage) + semaglutide (Ozempic) + empagliflozin (Jardiance). A1C is 7.9%. Which diabetes medication class should be AVOIDED because it can worsen HF via fluid retention?

Case 2 (CKD nuance). A 62-year-old woman with T2DM and CKD has eGFR 28 mL/min/1.73m². A1C 8.1%. She is taking metformin (Glucophage) 1000 mg twice daily. What is the most appropriate metformin action today?

Case 2 (after change). Metformin was stopped. You start dapagliflozin (Farxiga). Three weeks later she presents with nausea and malaise. Labs: glucose 210 mg/dL, anion gap 20, bicarbonate 16, serum ketones positive. What is the most likely diagnosis?

Case 2 (mechanism). Which mechanism best explains SGLT2 inhibitor–associated euglycemic DKA?

Case 3 (catabolic hyperglycemia). A 48-year-old man with T2DM presents with polyuria, polydipsia, weight loss. A1C 11.2%, fasting glucose 320 mg/dL. What is the best initial pharmacologic move?

Case 3 (titration). You start insulin glargine (Lantus) 10 units nightly and continue metformin. After 1 week, fasting glucose remains 190–220 mg/dL. Best next adjustment?

Case 3 (basal vs prandial). After titration, fasting glucose averages 105–120 mg/dL, but 2-hour post-meal glucose runs 220–260 mg/dL; A1C remains 8.3%. Best next step?

Case 4 (hypoglycemia in CKD). A 76-year-old man with T2DM and CKD stage 4 (eGFR 22) has syncope; EMS glucose is 48 mg/dL. Meds: glyburide (Diabeta), metformin (Glucophage), lisinopril. Which medication is the most likely cause?

Case 4 (mechanism of risk). Why is glyburide (Diabeta) especially dangerous in advanced CKD?

Case 5 (abdominal pain on GLP-1). A 59-year-old woman with T2DM and obesity started semaglutide (Ozempic) 8 weeks ago. She now has persistent severe epigastric pain radiating to the back with vomiting. Most concerning diagnosis?

Case 5 (pharmacologic effect). Which drug effect is most responsible for the common early GI intolerance of GLP-1 receptor agonists (e.g., semaglutide/Ozempic)?

Case 6 (DKA sequencing). A 23-year-old woman with type 1 diabetes presents with DKA. Glucose 480 mg/dL, pH 7.12, serum K 2.9 mEq/L. What is the best immediate next step?

Case 6 (threshold). Insulin therapy in DKA should be delayed until serum potassium is at least:

A 60-year-old with T2DM and established ASCVD (prior MI) is controlled on metformin (Glucophage) but A1C is 7.8%. eGFR 70. Which add-on has the strongest evidence for reducing major adverse cardiovascular events (MACE)?

A 66-year-old with T2DM and albuminuric CKD (UACR 900 mg/g) on ACE inhibitor has A1C 7.6%. eGFR 42. Which diabetes medication is most specifically associated with slowing CKD progression independent of glycemic effects?

A patient on canagliflozin (Invokana) asks why you advise holding it before major surgery. Most important reason?

A 58-year-old on metformin (Glucophage) is scheduled for a contrasted CT scan. eGFR 38. Best medication plan?

A patient on insulin glargine (Lantus) has fasting glucose at target but frequent nocturnal hypoglycemia. Which basal insulin change most reduces nocturnal hypoglycemia risk?

A 45-year-old with T2DM on metformin adds tirzepatide (Mounjaro/Zepbound). Which statement best describes tirzepatide’s pharmacology?

A patient with T2DM and gastroparesis needs additional glucose lowering. Which option is least likely to worsen gastroparesis symptoms?

A 71-year-old with T2DM has recurrent severe hypoglycemia on glipizide (Glucotrol). You want a replacement with minimal hypoglycemia risk and once-daily oral dosing. Best choice?

A 63-year-old with T2DM is on metformin (Glucophage) + sitagliptin (Januvia). You are considering adding a GLP-1 RA (Ozempic). Which change is most appropriate?

Which diabetes medication class is most likely to cause edema and weight gain via fluid retention and adipogenesis?

A 57-year-old with T2DM and osteoporosis risk needs add-on therapy. Which class is most associated with increased fracture risk?

A patient starts empagliflozin (Jardiance) and returns with vulvovaginal itching and discharge. Most likely adverse effect?

A patient with type 1 diabetes asks if an SGLT2 inhibitor could help with glucose control. Best response?

A 33-year-old pregnant patient with pregestational diabetes needs glucose-lowering therapy. Best pharmacologic choice?

A patient with T2DM on high-dose prednisone for asthma has marked post-lunch and evening hyperglycemia with near-normal fasting glucose. Which insulin strategy best targets steroid-induced hyperglycemia pattern?

Which insulin is best categorized as rapid-acting and typically used for mealtime coverage?

A patient on acarbose (Precose) develops symptomatic hypoglycemia after taking it with insulin. Best treatment for hypoglycemia in this situation?

A patient on insulin pump therapy presents with DKA after the infusion set dislodged. Compared with long-acting basal injection regimens, pump failure leads to more rapid DKA because pumps deliver:

A 64-year-old with T2DM and mild cognitive impairment needs a regimen with low hypoglycemia risk and simple dosing. Which option is least appropriate?

A patient with T2DM and prior pancreatitis needs add-on therapy. Which option is most prudent to avoid due to pancreatitis concern?

Which drug class is most likely to cause hypoglycemia independent of meal timing due to glucose-independent insulin release?

A patient with T2DM on basal-bolus insulin is started on semaglutide (Ozempic). Within 2 weeks, fasting glucose is frequently low. Most appropriate insulin adjustment strategy?

A patient with A1C 7.6% on metformin wants an oral add-on with minimal hypoglycemia and is concerned about UTIs/genital infections. Best choice?

A patient with T2DM and severe hypertriglyceridemia presents with abdominal pain and elevated lipase. Which diabetes medication should be held during evaluation because it can confound symptoms by causing significant GI effects?

A 56-year-old on saxagliptin (Onglyza) develops new HF symptoms; EF is reduced. Which statement best reflects the evidence signal?

A patient is on pioglitazone (Actos) and develops new edema and 8 lb weight gain. Which additional finding would most strongly prompt discontinuation?

A patient on basal insulin has been progressively uptitrated; now basal dose is very high and fasting glucose is only slightly above goal, but A1C remains elevated. This pattern most strongly suggests:

A 50-year-old with T2DM asks why GLP-1 RAs (Ozempic/Victoza/Trulicity) have low hypoglycemia risk when used alone. Best explanation?

A patient on insulin and acarbose (Precose) is hypoglycemic and only has a sucrose-containing beverage available. What is most accurate?

A 61-year-old with T2DM wants an agent that lowers A1C and also lowers systolic blood pressure modestly. Best match?

A patient with T2DM and recurrent UTIs is considering an SGLT2 inhibitor. Which counseling point is most appropriate?

A hospitalized patient with poor oral intake is taking home diabetes meds: metformin (Glucophage), empagliflozin (Jardiance), and glipizide (Glucotrol). Which is most appropriate to hold immediately due to high inpatient hypoglycemia risk with reduced intake?

A patient with T2DM is being discharged on basal insulin plus a GLP-1 RA. Which patient education point is most important to reduce hypoglycemia risk early?

Which medication is most likely to improve insulin sensitivity in adipose tissue and muscle (not insulin secretion)?

A 55-year-old with T2DM and obesity is choosing between semaglutide (Ozempic) and sitagliptin (Januvia) as add-on to metformin. Which statement is most accurate when comparing expected A1C and weight effects?