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TOPLINE:

One third of patients with type 2 diabetes (T2D) treated with metformin plus one of four common glucose-lowering drugs (insulin glargine U-100, glimepiride, liraglutide, or sitagliptin) experienced hospitalization over a 5-year period, with a small but significant benefit observed with liraglutide over glimepiride.

METHODOLOGY:

• The phase 3 GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) trial compared the effectiveness of several classes of glucose-lowering medications by randomly assigning 5047 patients with T2D of less than 10 years’ duration being treated with metformin and A1c levels of 6.8%-8.5% to receive insulin glargine U-100, glimepiride, liraglutide, or sitagliptin.
• Because patients with diabetes require acute medical care — including emergency department visits and inpatient hospitalizations — more frequently than those without, researchers conducted a secondary analysis of the GRADE trial to examine the association between assigned treatments and the risk for incident or recurrent hospitalization over a mean follow-up of 5 years.
• Participants were monitored quarterly for hospitalization (defined as inpatient admission ≥ 24 hours).

TAKEAWAY:

• Overall, 1636 (32.4%) participants (mean age at baseline visit, 59.7 years; 32.6% women) were hospitalized at least once, with 751 (14.9%) hospitalized more than once during the study period.
• Compared with patients who were never hospitalized, those who were hospitalized were older, more often men, more often White, less often Hispanic, and more likely to have a history of hypertension and had a higher baseline body mass index.
• The rates of initial and subsequent hospitalizations were similar across the four treatment groups; however, when the analysis was restricted to participants who received at least one dose of the assigned medication and attended at least one visit after randomization (N = 4830), those treated with liraglutide had a 22% lower risk for the incidence of first hospitalization than those treated with glimepiride (P = .022).
• Factors associated with an increased risk for future hospitalizations were A1c > 7.5%, the number of prior hospitalizations, and changes in the assigned treatment (P < .001 for all); initial assignment to liraglutide vs glimepiride reduced the hospitalization risk by 13%.

IN PRACTICE:

“Deteriorating glycemic control (reaching the secondary metabolic outcome) increased the risk for hospitalizations and highlights the substantial medical burden of type 2 diabetes and continued need for more effective and more durable glycemic control strategies,” the authors wrote.

SOURCE:

This study was led by Daniel S. Hsia, MD, Pennington Biomedical Research Center, Baton Rouge, Louisiana. It was published online on May 27, 2025, in Diabetes Care.

LIMITATIONS:

The stringent inclusion criteria limited the generalizability of the findings. The results represent a narrow range of drugs and may not apply to newer and increasingly common medications, such as sodium-glucose cotransporter 2 inhibitors and weekly glucagon-like peptide 1 receptor agonists.

DISCLOSURES:

GRADE was supported by grants from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, with additional support from the National Heart, Lung, and Blood Institute and the Centers for Disease Control and Prevention. The Department of Veterans Affairs provided resources and facilities. Some authors reported receiving grants, consulting fees, and payments and having contracts and other ties with multiple pharmaceutical companies and institutions.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.