AHRQ’s Comparative Effectiveness Research on Oral Medications for Type 2 Diabetes: A Summary of the Key Findings

Abstract

Type 2 diabetes mellitus is a major public health burden. Since the 2007 AHRQ systematic review of oral medications for type 2 diabetes, the FDA has approved several new drug classes. Therefore, in 2011, the original systematic review was updated with comparisons including the newer oral diabetes medications. The updated report expands beyond the scope of the original 2007 review by including comparisons of 2-drug combinations and the addition of more head-to-head comparisons, as well as additional adverse outcomes. A high strength of evidence showed that most medications were similarly efficacious at lowering hemoglobin A1c by about 1 absolute percentage point compared with baseline values. The addition of most oral medications to initial monotherapy further improved glycemiccontrol by lowering A1c by another 1 percentage point. The only exception was the DPP-4 inhibitor class, which did not lower A1c to the same extent as metformin when used as monotherapy. Overall, metformin was found to have a more favorable effect on body weight when compared with other medications. Two-drug combinations compared with each other demonstrated similar reductions in A1c levels. Metformin decreased low-density lipoprotein cholesterol (LDL-C) relative to pioglitazone, sulfonylureas,and DPP-4 inhibitors. Sulfonylureas had a 4-fold higher risk of mild-to-moderate hypoglycemia compared with metformin alone, and, in combination with metformin, had more than a 5-fold increased risk compared with metformin plus a thiazolidinedione. Thiazolidinediones had an increased risk of congestive heart failure relative to sulfonylureas, and an increased risk for bone fractures relative to metformin. Diarrhea occurred more often for metformin users compared with thiazolidinedione users. Although the long-term risks and benefits of diabetes medications remain unclear, the evidence supports the use of metformin as a first-line agent.

Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naïve Korean Type 2 Diabetic Patients

“…By the end of the study, the percentage of subject with initial HbA1c level ≥7.5% decreased by 2.5% to 2.7%. In previous studies, most OHAs decreased HbA1c level by about 1% when used as a monotherapy, and by about 2% when used as a combination therapy [8,9]. The differences between our results and those of previous studies might be due to the higher baseline HbA1c levels, drug-naïve characteristics, and lower insulin resistance of our subjects.…”

Antihyperglycemic effect of ipragliflozin, a sodium‐glucose co‐transporter 2 inhibitor, in combination with oral antidiabetic drugs in mice

“…Medications to treat T2DM are designed to correct one or more of these metabolic abnormalities. Several types of orally administered medications have been developed to control blood glucose levels in T2DM . Insulin secretagogues, such as sulfonylureas and meglitinides, stimulate insulin secretion from pancreatic β ‐cells.…”

“…The type of medication prescribed depends on certain patient characteristics, such as age and bodyweight. If blood glucose levels are not effectively managed with monotherapy, then the next step is combination therapy . The addition of another oral medication to the initial monotherapy often improves glycemic control .…”

“…If blood glucose levels are not effectively managed with monotherapy, then the next step is combination therapy . The addition of another oral medication to the initial monotherapy often improves glycemic control . However, given that many patients with T2DM lack adequate control of blood glucose levels, glycemic control is difficult to maintain, even with a combination of oral agents …”

Advantages and Pitfalls of Antihyperglycemic Combination Pills as First-Line Therapy in the Management of Type 2 Diabetes

“…The only exception is possibly the DPP IV inhibitor class, which does not lower HbA1c to the same extent as metformin when used as monotherapy. 29 Type 2 diabetes is the result of absolute or relative deficiency of insulin. These metabolic derangements account for increased endogenous production of glucose and decreased uptake and utilization in skeletal muscles and fat.…”