Intervention | Expected decrease in A1C with monotherapy (%) | Advantages | Disadvantages |
Initial therapy | |||
Lifestyle change to decrease weight and increase activity | 1 to 2 | Broad benefits | Insufficient for most within first year owing to inadequate weight loss and weight regain |
Metformin | 1 to 2 | Weight neutral | GI side effects, contraindicated with impaired kidney function (eGFR <30 mL/min/1.73 m2)* |
Additional therapy¶ | |||
Insulin (usually with a single daily injection of intermediate- or long-acting insulin initially) | 1.5 to 3.5 | No dose limit, rapidly effective, improved lipid profile | 1 to 4 injections daily, monitoring, weight gain, hypoglycemia, analogs are expensive |
Dual GLP-1 and GIP receptor agonist (once-weekly injections) | 2 to 2.5 | Weight loss | Requires injection, frequent GI side effects, expensive |
Sulfonylurea (shorter-acting agents preferred) | 1 to 2 | Rapidly effective | Weight gain, hypoglycemia (especially with glibenclamide or chlorpropamide) |
GLP-1 receptor agonist (oral or daily to weekly injections) | 0.5 to 2 | Weight loss, reduction in major adverse cardiovascular events (liraglutide, semaglutide, dulaglutide) in patients with established CVD and potentially for those at high risk for CVD | Requires injection, frequent GI side effects, expensive |
Thiazolidinedione | 0.5 to 1.4 | Improved lipid profile (pioglitazone), potential decrease in MI (pioglitazone) | Fluid retention, HF, weight gain, bone fractures, potential increase in MI (rosiglitazone) and bladder cancer (pioglitazone) |
Glinide | 0.5 to 1.5Δ | Rapidly effective | Weight gain, 3 times/day dosing, hypoglycemia |
SGLT2 inhibitor | 0.5 to 0.7 | Weight loss, reduction in systolic blood pressure, reduced cardiovascular mortality in patients with established CVD, improved kidney outcomes in patients with nephropathy | Vulvovaginal candidiasis, urinary tract infections, bone fractures, lower limb amputations, DKA |
DPP-4 inhibitor | 0.5 to 0.8 | Weight neutral | Possible increased risk of HF with saxagliptin, expensive |
Alpha-glucosidase inhibitor | 0.5 to 0.8 | Weight neutral | Frequent GI side effects, 3 times/day dosing |
Pramlintide | 0.5 to 1 | Weight loss | 3 injections daily, frequent GI side effects, long-term safety not established, expensive |
A1C: glycated hemoglobin; CVD: cardiovascular disease; DKA: diabetic ketoacidosis; DPP-4: dipeptidyl peptidase 4; eGFR: estimated glomerular filtration rate; GI: gastrointestinal; GIP: glucose-dependent insulinotropic polypeptide; GLP-1: glucagon-like peptide-1; HF: heart failure; MI: myocardial infarction; SGLT2: sodium-glucose cotransporter 2.
* Initiation is contraindicated with eGFR <30 mL/min/1.73 m2 and not recommended with eGFR 30 to 45 mL/min/1.73 m2.
¶ The order of listing of additional therapies does not indicate a preferred order of selection. The choice of additional therapy should be based on criteria discussed in the UpToDate topics on the management of hyperglycemia in diabetes mellitus.
Δ Repaglinide is more effective in lowering A1C than nateglinide.Do you want to add Medilib to your home screen?