1The two classes against each other
≠ marks rows where the two differ.
| Point of comparison | SGLT2 inhibitor | GLP-1 receptor agonist |
|---|---|---|
| Differs: Agents you will meet | Empagliflozin, dapagliflozin, canagliflozin | Semaglutide, liraglutide, dulaglutide; tirzepatide is a dual GIP and GLP-1 receptor agonist |
| Differs: Route | Oral, once daily | Injection, weekly or daily; semaglutide also comes as a tablet |
| Differs: Strongest organ case | Heart failure across the ejection-fraction range; CKD | Weight, MASLD and its inflammatory form MASH; ASCVD |
| Differs: Glucose effect as kidney function falls | Shrinks, while heart and kidney benefit persists | Largely kept |
| Differs: Cautions to counsel | Genital mycotic infection, volume depletion, euglycemic ketoacidosis, sick-day holds | Nausea and other GI effects, gallbladder events; boxed warning on thyroid C-cell tumors |
| Hypoglycemia on its own | Low | Low |
Indications and contraindications differ by agent; check each label before applying a class statement to a single drug.
2Why the A1c does not decide
The heart and kidney benefits of both classes came from outcome trials, and they appeared regardless of baseline A1c. The ADA Standards therefore separate two questions: which agent protects this patient’s organs, and what glucose-lowering remains to be done. A patient at goal A1c with heart failure still needs an SGLT2 inhibitor, and that is exactly the kind of stem built to tempt you into doing nothing.
Kidney function shapes the SGLT2 inhibitor decision in a specific way. The glucose-lowering effect fades as filtration falls, but the guidelines keep the drug for its organ effect well below the point where it stops lowering glucose. Those cut-points are expressed as eGFR, which is not the same number many renal dosing tables use; the difference is set out in CrCl vs eGFR for drug dosing.
2.1Weight as the main comorbidity
When obesity is the dominant problem, ADA 2026 points to the agents with the largest weight effect. Tirzepatide and semaglutide sit at the top of that list, and both also lower A1c substantially. A sulfonylurea or basal insulin can bring A1c down too, at the cost of weight gain and hypoglycemia, and that cost is the reason they rank lower when weight matters.
2.2When insulin enters
If injectable therapy is needed, ADA 2026 favors a GLP-1 RA for most patients before basal insulin, and keeps it alongside insulin once both are used, which limits weight gain and insulin dose. Fixed-ratio products combine the two in one pen.
For the rest of diabetes, thyroid and bone, see the endocrinology monograph.
3Match the organ to the class
Find the comorbidity in each stem first, then match it to the class. The A1c is there, but it is rarely the deciding number.
Study cases written by our editors, not BPS items. The real BCPS exam is computer-based multiple choice, answered in order with no going back.
Case 1 of 6 · 0 answered
How case rounds work
Pick an option to see the verdict and a note on every option. Keys while the round has focus: 1–5 or A–E answer, ← → move between cases. Nothing is saved or sent anywhere.
Case 01
A 58-year-old man with type 2 diabetes and a myocardial infarction 1 year ago takes metformin 1,000 mg twice daily, atorvastatin 80 mg daily, metoprolol succinate 50 mg daily, and aspirin 81 mg daily. A1c is 7.4%, BMI 33 kg/m², eGFR 82 mL/min/1.73 m², and LVEF is 55%. Which medication should be added?
Pick an option: the verdict and a note on every option open here.
Best answer: D.
ADA 2026 recommends a GLP-1 RA or SGLT2 inhibitor with proven cardiovascular benefit for established ASCVD independent of A1c and metformin use, and his obesity favors a high-efficacy GLP-1 RA such as semaglutide (SUSTAIN-6). Sitagliptin is the tempting choice because it is weight-neutral and well tolerated, but DPP-4 inhibitors are only cardiovascular-neutral. Glipizide causes weight gain and hypoglycemia without CV benefit, and pioglitazone causes weight gain and fluid retention.
- A
- Pioglitazone adds weight and fluid retention and is not the agent chosen for cardiovascular risk reduction here.
- B
- Glipizide brings hypoglycemia and weight gain with no cardiovascular protection.
- C
- Sitagliptin is well tolerated and weight-neutral, but DPP-4 inhibitors are only cardiovascular-neutral.
- D
- Correct. Established ASCVD calls for a GLP-1 RA or SGLT2 inhibitor with proven CV benefit, and his BMI 33 favors semaglutide.
Case 02
A 56-year-old woman with type 2 diabetes and CKD takes lisinopril 40 mg daily, metformin 1,000 mg twice daily, and atorvastatin 40 mg daily. BP is 126/78 mm Hg. Labs: eGFR 48 mL/min/1.73 m², urine albumin-to-creatinine ratio 450 mg/g, K 4.6 mEq/L, HCO3 25 mEq/L, A1c 7.0%. According to KDIGO 2024, which medication should be added to slow CKD progression?
Pick an option: the verdict and a note on every option open here.
Best answer: C.
KDIGO 2024 makes a maximally tolerated RAS inhibitor, an SGLT2 inhibitor and a statin the first-line triad for diabetic CKD with eGFR at least 20, and she is missing the SGLT2 inhibitor, which reduces kidney failure and CV events regardless of A1c. Finerenone is added when albuminuria persists despite RASi plus SGLT2 inhibitor, so it comes after empagliflozin. Adding losartan to lisinopril is dual RAS blockade, which raises hyperkalemia and AKI risk without benefit, and sodium bicarbonate is reserved for metabolic acidosis, which she does not have (HCO3 25 mEq/L).
- A
- Adding losartan to lisinopril is dual RAS blockade with hyperkalemia and AKI risk and no renal gain.
- B
- Finerenone comes after an SGLT2 inhibitor, for albuminuria that persists on RAS inhibitor plus SGLT2 inhibitor.
- C
- Correct. KDIGO 2024 pairs a maximal RAS inhibitor with an SGLT2 inhibitor at eGFR 20 or above; empagliflozin is the missing piece.
- D
- Bicarbonate treats metabolic acidosis, and her HCO3 of 25 mEq/L is normal.
Case 03
A 68-year-old man with HFpEF (LVEF 58%, NYHA class II) is euvolemic on furosemide 20 mg daily. He also takes lisinopril 20 mg daily for hypertension. BP is 128/76 mm Hg, HR 72 beats/minute (sinus rhythm). Labs: eGFR 55 mL/min/1.73 m², K 4.5 mEq/L. Which medication should be added to reduce his risk of heart failure hospitalization?
Pick an option: the verdict and a note on every option open here.
Best answer: A.
SGLT2 inhibitors are the cornerstone of HFpEF therapy (2022 AHA/ACC/HFSA Class 2a, EMPEROR-Preserved and DELIVER), reducing HF hospitalization regardless of diabetes. Sacubitril/valsartan is only Class 2b in HFpEF (PARAGON-HF missed its primary endpoint), so it is a weaker choice than an SGLT2 inhibitor. Ivabradine is indicated only in HFrEF with HR of at least 70 beats/minute, and digoxin has no role in HFpEF in sinus rhythm.
- A
- Correct. SGLT2 inhibitors reduce HF hospitalization in HFpEF (EMPEROR-Preserved, DELIVER) with or without diabetes.
- B
- Ivabradine is studied and indicated only in HFrEF with a sinus rate of at least 70.
- C
- Sacubitril/valsartan is a weaker recommendation in HFpEF because PARAGON-HF missed its primary endpoint.
- D
- Digoxin has no role in HFpEF with sinus rhythm.
Case 04
A 55-year-old man with type 2 diabetes, obesity (BMI 34 kg/m²) and HFrEF (LVEF 35%, NYHA class II) has biopsy-proven metabolic dysfunction-associated steatohepatitis (MASH) with stage F2 fibrosis. He takes metformin 1,000 mg twice daily, sacubitril/valsartan, metoprolol succinate and dapagliflozin. A1c is 7.8% and ALT 82 units/L. Which medication is most appropriate to add?
Pick an option: the verdict and a note on every option open here.
Best answer: B.
ADA 2026 prefers a GLP-1 RA with proven benefit in MASH for patients with diabetes and MASH, and semaglutide improves steatohepatitis and fibrosis while also lowering A1c and weight. Pioglitazone also improves MASH histology, but it causes fluid retention and is avoided in heart failure, which this patient has. Sitagliptin and glipizide have no proven liver benefit, and glipizide adds weight gain and hypoglycemia.
- A
- Sitagliptin has no proven benefit on steatohepatitis or fibrosis and does little for weight.
- B
- Correct. Semaglutide improves MASH histology and fibrosis while lowering A1c and weight, and it is safe with his HFrEF.
- C
- Pioglitazone helps MASH histology, but fluid retention makes it a poor choice with HFrEF.
- D
- Glipizide does nothing for the liver and adds hypoglycemia and weight gain.
Case 05
A 64-year-old man with type 2 diabetes and CKD has taken losartan 100 mg and empagliflozin 10 mg daily for 6 months. His UACR has gone from 680 to 610 mg/g, eGFR is 48 mL/min/1.73 m², K 4.4 mEq/L, BP 128/76 mm Hg, and A1c 7.0%. Which action is most appropriate?
Pick an option: the verdict and a note on every option open here.
Best answer: B.
Monitoring shows persistent albuminuria (UACR ≥30 mg/g) despite a maximal ARB and an SGLT2 inhibitor, so KDIGO and ADA recommend adding the nonsteroidal MRA finerenone, which reduces kidney and cardiovascular events; with eGFR 25–60 and K below 5.0 the starting dose is 10 mg daily, with K rechecked at 4 weeks. Combining an ACE inhibitor with an ARB increases hyperkalemia and AKI without benefit. Losartan above 100 mg exceeds the labeled maximum, and the SGLT2 inhibitor should continue until dialysis.
- A
- An ACE inhibitor on top of an ARB raises hyperkalemia and AKI risk without benefit.
- B
- Correct. Albuminuria persists on a maximal ARB plus an SGLT2 inhibitor, and with K 4.4 and eGFR 48 finerenone starts at 10 mg.
- C
- SGLT2 inhibitors are continued for kidney and heart protection even when albuminuria persists.
- D
- Losartan 100 mg is already the labeled maximum, and going higher has no supporting evidence.
Case 06
A 58-year-old woman with type 2 diabetes takes metformin 1,000 mg twice daily. A1c is 8.2%, BMI is 38 kg/m², eGFR is 82 mL/min/1.73 m², and she has no ASCVD, HF, or history of pancreatitis or medullary thyroid cancer. Knee osteoarthritis limits her walking, and she is starting an aquatic exercise program. Which medication should be added?
Pick an option: the verdict and a note on every option open here.
Best answer: C.
With obesity as her dominant comorbidity, ADA 2026 recommends a high-efficacy agent for both glucose and weight, and tirzepatide gives the largest A1c and weight reductions—complementing the adapted exercise plan, since weight loss also eases knee pain. Glipizide and insulin glargine lower A1c but cause weight gain and hypoglycemia. Pioglitazone also causes weight gain and fluid retention, working against her main treatment goal.
- A
- Pioglitazone adds weight and fluid, working against her main goal.
- B
- Glipizide lowers A1c but brings weight gain and hypoglycemia.
- C
- Correct. With obesity as her dominant comorbidity, tirzepatide offers the largest A1c and weight reductions.
- D
- Basal insulin is premature at an A1c of 8.2% and would add weight.
4Short answers on the two classes
Can a patient take an SGLT2 inhibitor and a GLP-1 RA together?
Yes. ADA 2026 supports combining them when a patient has indications for both, for example CKD and obesity, and the benefits appear additive.
Are SGLT2 inhibitors only for diabetes?
No. Dapagliflozin and empagliflozin carry heart failure and CKD indications without diabetes, which is why they also appear in heart failure GDMT.
Is tirzepatide a GLP-1 receptor agonist?
It acts on two receptors, GIP and GLP-1. Guidelines group it with the GLP-1 RAs for weight and glucose, and its label carries the same thyroid C-cell boxed warning.
Who should not get a GLP-1 RA?
The class is contraindicated with a personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2, and a history of pancreatitis calls for caution. Check the specific label.
5References
- ADA. 9. Pharmacologic Approaches to Glycemic Treatment: Standards of Care in Diabetes—2026. Diabetes Care, 2026. As of October 27, 2026.
- ADA. 11. Chronic Kidney Disease and Risk Management: Standards of Care in Diabetes—2026. As of October 27, 2026.
- KDIGO 2022 Clinical Practice Guideline for Diabetes Management in CKD. As of October 27, 2026.
- KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of CKD. As of October 27, 2026.
Next step
From reference to rehearsal
Move from reading to answering, on your phone or in the browser.
Pharmacotherapy Exam Prep 2026 is an app for iPhone and iPad only; there is no Android version. On any other phone or a computer, use the free practice set on this site in your browser.