Boxed Warnings
This biguanide's boxed warning describes a rare but serious buildup of acid in the blood, with risk rising in renal impairment, hypoxia, or sepsis.
Lactic acidosis
Metformin must not be started in this eGFR range and must be stopped entirely below an eGFR of 30.
eGFR 30 to 45 (do not start)
Along with A1C, this kidney function test should be checked at baseline and at least annually in every patient on metformin.
eGFR
Metformin's most common adverse effects, plus a distinctive taste disturbance, both often eased by the extended-release formulation.
Diarrhea, nausea, cramping, metallic taste
This drug class delays carbohydrate digestion by inhibiting intestinal alpha-glucosidase, but is rarely used in the US due to flatulence and bloating.
GLP-1 receptor agonists and tirzepatide carry a boxed warning for this rodent tumor finding, contraindicating use with a personal or family history of MTC or MEN 2.
Thyroid c-cell tumors
This lipid-lowering drug is an absolute contraindication with repaglinide because it dramatically raises repaglinide levels.
When the type of diabetes is unclear, checking islet autoantibodies plus this pancreatic beta-cell marker helps distinguish type 1 or LADA from type 2.
C-peptide
This second-generation sulfonylurea is best avoided in the elderly and in CKD, per the Beers criteria, because of active renal metabolites.
Glyburide
Linagliptin is the DPP-4 inhibitor that needs no renal dose adjustment because it is cleared through this route instead.
Hepatic
Pramlintide's boxed warning describes this specific event, occurring within 3 hours of dosing, mainly when combined with insulin.
Severe insulin-induced hypoglycemia
Afrezza, the inhaled ultra-rapid insulin, is contraindicated in patients with these two chronic lung conditions.
Patients starting an SGLT2 inhibitor should be told to urgently report this symptom, a warning sign of a rare, life-threatening perineal infection.
Perineal pain or swelling
DPP-4 inhibitors as a class can cause this joint symptom, along with rare pancreatitis and a rare autoimmune blistering skin condition.
Arthralgia and bullous pemphigoid
This drug class closes the beta-cell KATP channel like a sulfonylurea, but acts rapidly and briefly, dosed with each meal and skipped if a meal is skipped.
Meglitinides
Pioglitazone and rosiglitazone share a boxed warning for causing or worsening this condition, contraindicating use in NYHA class III to IV.
Heart failure
SGLT2 inhibitors should be held for roughly this many days before major surgery to lower the risk of euglycemic DKA.
3-4 days
A patient started on teplizumab needs these two labs monitored, given the risks of lymphopenia and liver enzyme elevation.
What are a CBC and liver enzymes?
Beyond the class's genital infection and euglycemic DKA risks, this SGLT2 inhibitor carries an added signal for lower-limb amputation and fracture.
Canagliflozin
This first-in-class dual incretin agonist activates both the GIP and GLP-1 receptors, producing the largest A1C and weight reductions of any available agent.
Tirzepatide
This fixed-dose combination pairs insulin degludec with liraglutide, carrying both an insulin hypoglycemia risk and the GLP-1 thyroid C-cell boxed warning.
Xultophy
This entire drug class is contraindicated in pregnancy due to effects on renal tubular maturation in the second and third trimesters.
SGLT2i
This drug class commonly causes nausea, vomiting, diarrhea, and constipation, which is exactly why dosing is titrated upward slowly.
GLP1 and GIP
This PPAR-gamma agonist improves insulin sensitivity without causing hypoglycemia and shows benefit in MASH, despite carrying a heart failure boxed warning.
Pioglitazone