Agents Used for Treatment of Type 1 or Type 2 Diabetes | ||||||
| MECHANISM OF ACTION | EXAMPLESa | HbA1C REDUCTION (%)b | AGENT-SPECIFIC ADVANTAGES | AGENT-SPECIFIC DISADVANTAGES | CONTRAINDICATIONS | |
|---|---|---|---|---|---|---|
| Oral | ||||||
| Biguanidesc * | ↓Hepatic glucose production | Metformin | 1-2 | Weight neutral, do not cause hypoglycemia, inexpensive, extensive experience, ↓ CV events | Diarrhea, nausea, lactic acidosis, vitamin B12 deficiency | Renal insufficiency (see text for GFR <45 mL/min), CHF, radiographic contrast studies, hospitalized pts, acidosis |
| α-Glucosidase inhibitorsc** | ↓GI glucose absorption | Acarbose, miglitol, voglibose | 0.5-0.8 | Reduce postprandial glycemia | GI flatulence, liver function tests | Renal/liver disease |
| Dipeptidyl peptidase IV inhibitorsc *** | Prolong endogenous GLP-1 action; ↑ Insulin, ↓ glucagon | Alogliptin, linagliptin, saxagliptin, sitagliptin, vildagliptin | 0.5-0.8 | Well tolerated, do not cause hypoglycemia | Angioedema/urticarial and immune-mediated dermatologic effects | Reduced dose with renal disease |
| Insulin secretagogues: Sulfonylureasc * | ↑Insulin secretion | Glibornuride, gliclazide, glimepiride, glipizide, gliquidone, glyburide, glyclopyramide | 1-2 | Short onset of action, lower postprandial glucose, inexpensive | Hypoglycemia, weight gain | Renal/liver disease |
| Insulin secretagogues: Nonsulfonylureasc *** | ↑Insulin secretion | Mitiglinide nateglinide, repaglinide | 0.5-1.0 | Short onset of action, lower postprandial glucose | Hypoglycemia | Renal/liver disease |
| Sodium-glucose cotransporter 2 inhibitors*** | ↑renal glucose excretion | Canagliflozin, dapagliflozin, empagliflozin, ertugliflozin | 0.5-1.0 | Do not cause hypoglycemia, ↓ weight and BP; see text for CVD effect | Urinary and genital infections, polyuria, dehydration, exacerbate tendency to hyperkalemia and DKA; see text | Moderate renal insufficiency, insulin-deficient DM |
| Thiazolidinedionesc *** | ↓Insulin resistance, ↑ glucose utilization | Pioglitazone, rosiglitazone | 0.5-1.4 | Lower insulin requirements | Peripheral edema, CHF, weight gain, fractures, macular edema | CHF, liver disease |
| Parenteral | ||||||
| Amylin agonistsc,d*** | Slow gastric emptying, ↓ glucagon | Pramlintide | 0.25-0.5 | Reduce postprandial glycemia, weight loss | Injection, nausea, ↑ risk of hypoglycemia with insulin | Agents that also slow GI motility |
| GLP-1 receptor agonistsc *** | ↑Insulin, ↓ glucagon, slow gastric emptying, satiety | Albiglutide, dulaglutide, exenatide, liraglutide, lixisenatide, semaglutide | 0.5-1.0 | Weight loss, do not cause hypoglycemia; see text for CVD effect | Injection, nausea, ↑ risk of hypoglycemia with insulin secretagogues | Renal disease, agents that also slow GI motility; medullary carcinoma of thyroid, pancreatic disease |
| Insulinc ,d **** | ↑Glucose utilization, ↓ hepatic glucose production, and other anabolic actions | See text | Not limited | Known safety profile | Injection, weight gain, hypoglycemia | |
| Medical nutrition therapy and physical activityc * | ↓Insulin resistance, ↑ insulin secretion | Low-calorie, low-fat diet, exercise | 1-3 | Other health benefits | Compliance difficult, long-term success low | |
a Examples are approved for use in the United States; others are available in other countries. Examples may not include all agents in the class.
b HbA1c reduction (absolute) depends partly on starting HbA1c.
c Used for treatment of type 2 diabetes.
d Used in conjunction with insulin for treatment of type 1 diabetes. Cost of agent in the United States: * low, ** moderate, *** high, **** variable.
Note: Some agents used to treat type 2 DM are not included in table (see text).
Abbreviations: ACE, angiotensin-converting enzyme; CHF, congestive heart failure; CV, cardiovascular; GI, gastrointestinal; HbA1c, hemoglobin A1c.