CAROLINA Finds No Differences Between Tradjenta and Glimepiride Heart Health Outcomes
Previous studies have suggested that a type of medication called sulfonylureas, particularly Orinase (tolbutamide), may be unsafe for the heart. The FDA currently has a product-label warning for heart-related death for all sulfonylureas.
The trial evaluated the CV safety of 5 mg once-daily linagliptin vs. glimepiride, in addition to standard of care, in 6,033 adults with type 2 diabetes and increased CV risk or established CVD. The median follow-up was the longest period studied for a DPP-IV inhibitor CV outcomes trial, according to the two companies.
The overall safety profile of linagliptin in CAROLINA was consistent with previous data, and no new safety signals were observed, according to the release.
New CAROLINA study results, however, demonstrated that the DPP-4 inhibitor Tradjenta (linagliptin) and the sulfonylurea glimepiride are equally safe for the heart in people with type 2 diabetes.
The findings follow data from the CARMELINA trial presented in October at the European Association for the Study of Diabetes. In that study, linagliptin demonstrated CV safety and a neutral effect for hospitalization for heart failure and kidney outcomes vs. placebo among adults with type 2 diabetes, established CVD and/or chronic kidney disease.
The CAROLINA trial looked specifically at non-fatal heart attacks, non-fatal strokes, and heart-related death. Since we have evidence that Tradjenta is no more dangerous than placebo (a “nothing” pill), there’s reason to believe that glimepiride also poses no heart safety risk – though we don’t know if this applies to other sulfonylureas like glipizide, gliclazide, and glibenclamide.
Interestingly, although sulfonylureas are generally associated with weight gain, the trial also showed no difference between Tradjenta and glimepiride on changes in weight. Participants lost an average of small weight in both groups – because people were really “looked after” in the trials, it’s unlikely that this weight loss would happen with glimepiride in the real world.
There were also no significant differences in A1C reduction; both groups experienced an initial drop in A1C that creeped back up to the starting level of 7.1%.
However, sulfonylureas are known to carry a greater risk of hypoglycemia than other type 2 diabetes medications. CAROLINA confirmed increased hypoglycemia with glimepiride, showing a 77% increased risk of hypoglycemia overall; 38% of those on glimepiride experienced hypoglycemia, compared to 11% of those on Tradjenta.
Looking more closely, glimepiride had an 85% increased risk of severe hypoglycemia (low blood sugar requiring assistance from a third party) and a 93% increased risk of hospitalization for hypoglycemia. This alone is reason to avoid glimepiride if at all possible. If not, we encourage people to check blood glucose levels as frequently as possible.
Though Tradjenta clearly has the upper hand on hypoglycemia, those who are on glimepiride due to its lower cost can be more assured about heart safety.
www red DiabetologNytt