Important similarities and differences of 6 non-insulin antihyperglycemic drug classes were highlighted in a recently published model-based meta-analysis, allowing for an enhanced patient and physician understanding of type 2 diabetes treatment options.

The analysis included data from 229 randomized controlled studies with a total of 121,914 patients. The study authors compared the effects of approved doses of dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide 1 receptor agonists (GLP-1RAs), sodium–glucose cotransporter 2 (SGLT2) inhibitors, thiazolidinediones (TZD), sulfonylureas (SU), and metformin on HbA1c, body weight, and hypoglycemic risk. “To ensure fair and unbiased treatment comparisons, the analyses adjusted for important differences between studies, including duration of treatment, baseline glycated hemoglobin, and drug dosages,” the study authors stated.

Results of the analysis found that GLP-1RAs exhibited the greatest reduction in HbA1c overall (max: 1.77% with semaglutide 1.0mg). The smallest reduction in HbA1c was seen in patients taking DPP-4 inhibitors (0.58%–0.72%). The study authors also reported that reductions in body weight were seen in patients taking SGLT2 inhibitors (1.7–2.4kg), GLP-1RAs (except albiglutide; 0.4–3.8kg), and metformin (approximately 0.5kg). Small increases in body weight were observed in patients taking DPP-4 inhibitors, while larger increases (2–3kg) were seen in patients taking SUs and TZDs.

Related Articles

“Hypoglycemia risk was highest with sulfonylureas, although gliclazide was notably lower,” the study authors reported. They added, “Hypoglycemia risk for DPP-4 inhibitors, SGLT2 inhibitors and thiazolidinediones was generally very low, but increased slightly for both GLP-1RAs and metformin.”

In this meta-analysis, several conclusions were drawn about the effects of 6 antihyperglycemic medication classes on HbA1c, body weight, and hypoglycemic risk. The study authors noted, however, that the choice of an agent always depends on the “unique patient characteristics and benefit-risk profile of each drug.”


Maloney A, Rosenstock J, Fonseca V. A Model‐Based Meta‐Analysis of 24 Antihyperglycemic Drugs for Type 2 Diabetes: Comparison of Treatment Effects at Therapeutic Doses. Clinical Pharmacology & Therapeutics. DOI: 10.1002/CPT.1307.