You can add any third drug you want to the standard metformin-sulfonylurea combination used to treat type 2 diabetes, including insulin, alpha-glucosidase inhibitors, thiazolidinediones, glucagon-like peptide-1 agonists, or dipeptidyl peptidase-4 inhibitors. None of them provides a decisive superiority in blood glucose control. That’s the conclusion of a Brazilian meta-study of 18 drug trials published in the May 17, 2011, issue of the Annals of Internal Medicine.
The study tracked research in which a third drug was introduced after the metformin-sulfonylurea combination failed to deliver desired blood sugar control. University researchers based in Porto Alegre looked through databases such as MEDLINE, EMBASE, Cochrane Library, LILACS, and ClinicalTrials.gov for trials that assessed the effects of adding a third drug to a regimen of blood sugar control. The studies had to be at least six months long and involve type 2 patients at least 18 years old with A1c levels of 7% or higher. Outcome reports had to include changes in weight and A1c levels and frequency of severe hypoglycemic episodes.
The study found a fairly narrow range of reductions in A1c levels–from .7% for alpha-glucosidase inhibitors to 1.08% for insulin. There were weight gains associated with insulins and thiazolidinediones (2.84 kg/6.25 lbs and 4.25 kg/9.35 lbs, respectively), while glucagon-like peptide-1 agonists were associated with a mean weight loss of 1.63 kg/3.6 lbs. Insulins were associated with twice the absolute number of severe hypoglycemic episodes compared to all of the non-insulin agents surveyed.
The meta-study’s authors say that their comparisons are indirect at best, given differences in the lengths and methodologies of the trials they studied. They concluded, however, that differences in the effects of third drugs added to the metformin-sulfonylurea mix are not significant enough to prevent doctors and type 2 patients from determining which third drug to add on a case-by-case basis.