ROCKVILLE, MD — Not many studies have looked at the comparative effectiveness of commonly used glucose-lowering medications, when added to metformin, on preventing microvascular and cardiovascular disease outcomes in Type 2 diabetes.
That issue was addressed in a recent study involving VA researchers in Cincinnati and Cleveland; Seattle; and Aurora, CO. The Glycemia Reduction Approaches in Diabetes (GRADE) study group, based at George Washington University, assessed the comparative effectiveness of four commonly used glucose-lowering medications, added to metformin, in achieving and maintaining a glycated hemoglobin level of less than 7.0% in participants with Type 2 diabetes. The randomly assigned therapies were insulin glargine U-100, glimepiride, liraglutide and sitagliptin.
This study, published in the New England Journal of Medicine, looked at prespecified secondary outcomes with related to microvascular and cardiovascular disease.1
Included outcomes:
- hypertension and dyslipidemia,
- confirmed moderately or severely increased albuminuria or an estimated glomerular filtration rate of less than 60 ml per minute per 1.73 m2 of body-surface area,
- diabetic peripheral neuropathy assessed with the Michigan Neuropathy Screening Instrument,
- cardiovascular events (major adverse cardiovascular events [MACE],
- hospitalization for heart failure, or
- an aggregate outcome of any cardiovascular event) and death.
Results indicated that, during a mean 5.0 years of follow-up in 5,047 participants, no significant differences among the interventions were identified related to the development of hypertension or dyslipidemia or to microvascular outcomes. Researchers reported that the mean overall rate (i.e., events per 100 participant-years) of moderately increased albuminuria levels was 2.6, of severely increased albuminuria levels 1.1, of renal impairment 2.9 and of diabetic peripheral neuropathy 16.7.
Furthermore, according to the study, differences in MACE (overall rate, 1.0), hospitalization for heart failure (0.4), death from cardiovascular causes (0.3) or all deaths (0.6) were not found among the treatment groups. Small differences were noted with rates of any cardiovascular disease, with 1.9, 1.9, 1.4 and 2.0 in the glargine, glimepiride, liraglutide and sitagliptin groups, respectively.
“When one treatment was compared with the combined results of the other three treatments, the hazard ratios for any cardiovascular disease were 1.1 (95% confidence interval [CI], 0.9 to 1.3) in the glargine group, 1.1 (95% CI, 0.9 to 1.4) in the glimepiride group, 0.7 (95% CI, 0.6 to 0.9) in the liraglutide group, and 1.2 (95% CI, 1.0 to 1.5) in the sitagliptin group,” the authors advised.
While the findings possibly point to differences among the groups in the incidence of any cardiovascular disease, medications did not appear to make any differences in the incidences of microvascular complications and death among the four treatment groups.
“Long-term complications of type 2 diabetes mellitus, including microvascular and cardiovascular disease, account for most illness, deaths, and costs associated with this condition,” according to background information in the report. “Clinical trials have shown a benefit of decreased chronic hyperglycemia on diabetes-specific microvascular complications. In addition, trials have shown that some new classes of glucose-lowering medication have beneficial effects with respect to cardiovascular disease and kidney disease, largely in participants with preexisting disease, whereas other medications have been shown to have neutral effects or potentially harmful side effects.”
- GRADE Study Research Group, Nathan DM, Lachin JM, Bebu I, Burch HB, et. al. Glycemia Reduction in Type 2 Diabetes – Microvascular and Cardiovascular Outcomes. N Engl J Med. 2022 Sep 22;387(12):1075-1088. doi: 10.1056/NEJMoa2200436. PMID: 36129997.
