
Am Fam Physician. 2022;105(6):675-677
Author disclosure: No relevant financial relationships.
Key Points for Practice
• To reduce overall mortality in patients with type 2 diabetes mellitus, the BMJ/MAGIC Group recommends prescribing SGLT-2 inhibitors in those with cardiovascular disease and/or chronic kidney disease or three or more risk factors for cardiovascular disease.
• GLP-1 receptor agonists are reasonable alternatives to SGLT-2 inhibitors in patients with similar risk profiles because this drug class also improves mortality, although to a lesser extent.
• Although SGLT-2 inhibitors and GLP-1 receptor agonists do not increase the risk of severe hypoglycemia, SGLT-2 inhibitors increase the risk of genital infections, and GLP-1 agonists have gastrointestinal adverse effects, especially at initiation and with high doses.
From the AFP Editors
Guideline Applicability

SGLT-2 Inhibitors

Male sex |
Asian, African, or Hispanic ethnicity |
Age > 60 years |
Family history of cardiovascular or kidney disease |
A1C ≥ 6.5% |
Current smoker |
Uncontrolled hypertension (≤ 140/90 mm Hg) |
Dyslipidemia (total cholesterol ≥ 200 mg per dL [5.18 mmol per L] or HDL cholesterol < 39 mg per dL [1.01 mmol per L]) |
In low-risk patients with less than three risk factors, SGLT-2 inhibitors still improve mortality, but absolute benefits are small. For patients who wish to reduce their cardiovascular and renal risk, SGLT-2 inhibitors are reasonable.
GLP-1 Receptor Agonists
GLP-1 receptor agonists improve mortality but to a lesser extent than SGLT-2 inhibitors. SGLT-2 inhibitors are superior to GLP-1 receptor agonists in improving cardiovascular and renal outcomes, except for nonfatal stroke.
The BMJ/MAGIC Group suggests GLP-1 receptor agonists as an alternative to SGLT-2 inhibitors for patients with type 2 diabetes, cardiovascular disease, and chronic kidney disease. In these very high-risk patients, GLP-1 receptor agonists reduce overall mortality, with an NNT of 42 (95% CI, 29 to 84) over five years.
GLP-1 receptor agonists reduce mortality in lower-risk patients, although absolute benefits are smaller. For patients with cardiovascular disease but not chronic kidney disease, GLP-1 receptor agonists reduce overall mortality, with an NNT of 59 (95% CI, 40 to 112) over five years. In patients with chronic kidney disease but not cardiovascular disease, the NNT is 77 (95% CI, 56 to 167) over five years.
Although GLP-1 receptor agonists improve mortality in low-risk patients, the absolute benefits are very small. For patients who wish to reduce their cardiovascular and renal risk, SGLT-2 inhibitors are preferred, but GLP-1 receptor agonists are reasonable.
Shared Decision-Making
Although SGLT-2 inhibitors are more effective than GLP-1 receptor agonists, benefits are similar. Prescribing choices should be based on patient preferences, medication adverse effects, and cost.
SGLT-2 inhibitors require monitoring for dizziness, hypotension, and renal dysfunction within three months of initiation and are contraindicated when glomerular filtration rate is reduced, usually to less than 30 mL per kg per 1.73 m2. Although SGLT-2 inhibitors increase the risk of genital infections, they do not appear to increase rates of Fournier gangrene or amputations. Tolerability to GLP-1 receptor agonists can be limited by gastrointestinal events, and starting at a low dose with slow titration is recommended. GLP-1 receptor agonists cannot be used in combination with dipeptidyl-peptidase 4 inhibitors. Most SGLT-2 inhibitors (except semaglutide) are available only by injection and require storage below 86°F (30°C).
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