Table 1.
Commonly Used Antihyperglycemic Agents Used for Type 2 Diabetes With HbA1c Above Target in the Setting of Current Use, Contraindication, or Intolerance With Combination Metformin, SGLT2 Inhibitors, and GLP-1 RA
| Antihyperglycemic Class | Mechanism (Range of HbA1c Change) | Risks/Drawbacks | Benefits | Factors to Consider in CKD/Transplant/Dialysis |
|---|---|---|---|---|
| Sulfonylureas (glipizide, glyburide, glimepiride, gliclazide) | Increased insulin secretion (0.8%-1.5%) | Hypoglycemia, weight gain | Inexpensive | - Glipizide and gliclazide are safer in CKD; not renally cleared, no active metabolites185,186 - Glyburide and glimepiride pose increased hypoglycemia risk - Glyburide and glimepiride should not be used with eGFR <60 and <30 mL/min/1.73 m2, respectively187,188 - Glyburide and glimepiride effectively increase cyclosporine levels; glipizide does not189,190 - Cotrimoxazole combined with glipizide increases risk for hypoglycemia191 |
| DPP-4 inhibitors (linagliptin, sitagliptin, saxagliptin, alogliptin) | Decreased breakdown of GLP-1 (0.5%-0.8%) | Do not use with GLP-1 RA | None | - Only linagliptin does not need dose adjustment in CKD192 - Cyclosporine and itraconazole increase saxagliptin levels, so dose should be reduced193 |
| Thiazolidinediones (pioglitazone) | Increased insulin sensitivity (0.5%-1.4%) | Fluid retention194; fracture risk194,195 | Inexpensive, decreased insulin needs | - No dose adjustments required188,196 - Safe in kidney transplantation197 |
| Glinides (nateglinide, repaglinide) | Rapid, short-lived insulin secretion with meals (0.5%-0.8%) | Hypoglycemia, weight gain | Reduces postprandial hyperglycemia | - Repaglinide safer in CKD; not renally cleared, but if eGFR <30 mL/min/1.73 m2, use with caution198,199 - Nateglinide has active metabolites that are renally cleared, so if eGFR <60 mL/min/1.73 m2, increased hypoglycemia risk198,199 - Nateglinide cleared by hemodialysis198 - Cyclosporine and itraconazole increase repaglinide levels200 |
| α-Glucosidase inhibitors (acarbose, miglitose) | Delays carbohydrate absorption in small intestine (0.5%-0.8%) | Flatulence, diarrhea | Reduces postprandial hyperglycemia | - Miglitol renally excreted, so if eGFR <60 mL/min/1.73 m2, not recommended186,201 - Acarbose minimally absorbed, but metabolites renally cleared, so if eGFR <30 mL/min/1.73 m2, not recommended186,201 |
| Insulin | Exogenous insulin | Hypoglycemia, injectable, weight gain | None, no dose limitations or ceiling on HbA1c reduction | - Renally metabolized and doses should be adjusted with decreasing eGFR, particularly rapid-acting insulin202,203 - Rapid-acting insulins given after meal may be helpful in patients with gastroparesis |
Abbreviations: CKD, chronic kidney disease; DPP-4, dipeptidyl peptidase 4; eGFR, estimated glomerular filtration rate; GLP-1, glucagon-like peptide 1; RA, receptor agonist; HbA1c, hemoglobin A1c.