Summary of glucose-lowering interventions
| Intervention | Expected decrease in A1C with monotherapy (%) | Advantages | Disadvantages |
|---|---|---|---|
| Tier 1: well-validated core | |||
| Step 1: initial therapy | |||
| Lifestyle to decrease weight and increase activity | 1.0–2.0 | Broad benefits | Insufficient for most within first year |
| Metformin | 1.0–2.0 | Weight neutral | GI side effects, contraindicated with renal insufficiency |
| Step 2: additional therapy | |||
| Insulin | 1.5–3.5 | No dose limit, rapidly effective, improved lipid profile | One to four injections daily, monitoring, weight gain, hypoglycemia, analogues are expensive |
| Sulfonylurea | 1.0–2.0 | Rapidly effective | Weight gain, hypoglycemia (especially with glibenclamide or chlorpropamide) |
| Tier 2: less well validated | |||
| TZDs | 0.5–1.4 | Improved lipid profile (pioglitazone), potential decrease in MI (pioglitazone) | Fluid retention, CHF, weight gain, bone fractures, expensive, potential increase in MI (rosiglitazone) |
| GLP-1 agonist | 0.5–1.0 | Weight loss | Two injections daily, frequent GI side effects, long-term safety not established, expensive |
| Other therapy | |||
| α-Glucosidase inhibitor | 0.5–0.8 | Weight neutral | Frequent GI side effects, three times/day dosing, expensive |
| Glinide | 0.5–1.5a | Rapidly effective | Weight gain, three times/day dosing, hypoglycemia, expensive |
| Pramlintide | 0.5–1.0 | Weight loss | Three injections daily, frequent GI side effects, long-term safety not established, expensive |
| DPP-4 inhibitor | 0.5–0.8 | Weight neutral | Long-term safety not established, expensive |
↵a Repaglinide more effective in lowering A1C than nateglinide. CHF, congestive heart failure; GI, gastrointestinal; MI, myocardial infarction.