TOPLINE:

When analyzed via continuous glucose monitoring (CGM), incretin-based medications such as liraglutide and sitagliptin demonstrated superior glycemic control over insulin glargine and glimepiride in patients with type 2 diabetes (T2D), achieving a higher time in range (TIR) and lower glucose variability. Glimepiride showed the poorest performance with the lowest TIR and more than double the number of hypoglycemic episodes compared with other medications.

METHODOLOGY:

• Glycemic management metrics derived from CGM are increasingly recognized as important therapeutic targets, providing unique information about glucose variability beyond what A1c can reveal.
• Researchers conducted a CGM substudy within the GRADE comparative effectiveness trial, which randomly assigned patients with T2D of less than 10 years’ duration to add one of four glucose-lowering medications (insulin glargine U-100, glimepiride, liraglutide, or sitagliptin) to metformin therapy.
• Between 2018 and 2020, about 4 years into GRADE, participants underwent a masked 2-week CGM session conducted at a median of 2.4 years after enrollment; the analysis included 1080 participants (mean age, 59.5 years; 39.5% women) in the on-treatment cohort who completed usable monitoring while remaining on their assigned study medications.
• Most participants (84%) were taking the protocol target metformin dose of 2000 mg/d, and median daily doses of randomized medications were as follows: liraglutide, 1.8 mg; glimepiride, 3.0 mg; sitagliptin, 100 mg; and insulin glargine, 0.3 units/kg.
• CGM readings included average glucose levels (mg/dL), glycemic variability as the percentage coefficient of variation, percent TIR of 70-180 mg/dL and time in tight range of 70-140 mg/dL, percent time above range > 180 mg/dL and above very high range > 250 mg/dL, and percent time below range < 70 mg/dL and below very low range < 54 mg/dL; hypoglycemia was defined as 15 minutes or more with glucose levels < 54 mg/dL, and prolonged hypoglycemia was defined 120 minutes or more with glucose levels < 54 mg/dL.

TAKEAWAY:

• Liraglutide produced the lowest mean A1c levels (6.7% vs 6.8% with sitagliptin and 6.9% with both glimepiride and glargine); CGM-derived average glucose showed the same trend, although it did not reach statistical significance.
• Sitagliptin and liraglutide groups achieved the highest TIR at 84.2% and 83.4%, respectively, compared with glargine at 80.1% and glimepiride at 76.3% (P < .001 for overall treatment effect); the mean time below range was lowest for sitagliptin (3.6%) and liraglutide (4.9%), intermediate for glargine (5.6%), and highest for glimepiride (8.6%).
• Glimepiride demonstrated the highest glucose variability, with a mean percentage coefficient of variation of 30.7% compared with glargine at 29.2%; however, liraglutide and sitagliptin showed lower variability at 25.4% and 24.9%, respectively (P < .001 for overall treatment effect).
• Participants on glimepiride also experienced on average at least twice as many hypoglycemic episodes and prolonged episodes per person as those in the other treatment groups (P < .001 for all pairwise comparisons involving glimepiride).

IN PRACTICE:

“CGM is a powerful tool to characterize how diabetes drugs work in practice, and this work supports further research into the value of CGM, in conjunction with [A1c], as a guide to management decisions,” the authors wrote.

SOURCE:

This study was led by Richard M. Bergenstal, International Diabetes Center, HealthPartners Institute in Minneapolis. It was published online in Diabetes Care.

LIMITATIONS:

The analyses were limited to a single 2-week CGM assessment in a subset of the overall GRADE cohort, conducted at postrandomization timepoints that varied across individuals. The study used an early generation of masked CGM sensors that may have yielded higher absolute rates of hypoglycemia than current versions. Early glycemic failure and adoption of rescue insulin in the sitagliptin group could have resulted in lower glucose levels in the on-treatment cohort.

DISCLOSURES:

The GRADE study was supported primarily by the National Institute of Diabetes and Digestive and Kidney Diseases, with additional support from other sources. Several authors reported receiving clinical trial contracts and investigator grants, institutional research funding, consulting fees, payments and support for meeting attendance, provision of research supplies/devices, an institutional patent, participation on data safety monitoring boards, and leadership roles in industry or academia.

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